<SEC-DOCUMENT>0001140361-21-040536.txt : 20211207
<SEC-HEADER>0001140361-21-040536.hdr.sgml : 20211207
<ACCEPTANCE-DATETIME>20211207060245
ACCESSION NUMBER:		0001140361-21-040536
CONFORMED SUBMISSION TYPE:	8-K
PUBLIC DOCUMENT COUNT:		14
CONFORMED PERIOD OF REPORT:	20211206
ITEM INFORMATION:		Entry into a Material Definitive Agreement
ITEM INFORMATION:		Financial Statements and Exhibits
FILED AS OF DATE:		20211207
DATE AS OF CHANGE:		20211207

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			IONIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				330336973
		STATE OF INCORPORATION:			CA
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		8-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		211474607

	BUSINESS ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010
		BUSINESS PHONE:		7609319200

	MAIL ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ISIS PHARMACEUTICALS INC
		DATE OF NAME CHANGE:	19930328
</SEC-HEADER>
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      <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 14pt; font-weight: bold;">SECURITIES AND EXCHANGE COMMISSION</div>

      <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 12pt; font-weight: bold;">Washington, D.C.&#160; 20549</div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CURRENT REPORT</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the
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                <div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))</span></div>
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      <div>&#160;</div>

      <div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Securities registered pursuant to Section 12(b) of the Act:</div>

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              <div style="text-align: center; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Title of each class</div>
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    <td style="width: 2%; vertical-align: top;">&#160;</td>

    <td style="width: 20%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Trading symbol</div>
            </td>

    <td style="width: 2%; vertical-align: top;">&#160;</td>

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    <td style="width: 34%; vertical-align: top; text-align: center;"><ix:nonNumeric name="dei:Security12bTitle" id="Fact_03233a20555b498fbec13cc79c2403bf" contextRef="c20211206to20211206">Common Stock, $.001 Par Value</ix:nonNumeric><br />
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    <td style="width: 2%; vertical-align: top;">&#160;</td>

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              <div style="text-align: center; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_fcce56880a58455b8870907b1c847746">The Nasdaq Stock Market, LLC</span><br />
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      <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (Section 230.405 of this
        chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (Section 240.12b-2 of this chapter).</div>

      <div> <br />
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              <div style="text-align: right; font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Emerging growth company</div>
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      <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new
        or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.&#160; &#9744; &#160;<span style="font-size: 10pt; font-family: Wingdings; color: #000000;">&#160; </span></div>

      <div>&#160;</div>

      <div>
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      <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 1.01 Entry into a Material Definitive Agreement.</div>

      <div>&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On December 6, 2021, Ionis Pharmaceuticals, Inc. (the &#8220;Company&#8221;), issued a press release announcing that the Company has entered into a strategic
        collaboration agreement with AstraZeneca to develop and commercialize eplontersen, the Company&#8217;s investigational antisense medicine for the treatment of transthyretin amyloidosis (ATTR).</div>

      <div>&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A copy of this press release is attached as Exhibit 99.1 to this Current Report and incorporated herein by reference.</div>

      <div>&#160;</div>

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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 9.01.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financial Statements and Exhibits.</div>
            </td>

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      <div>&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(d) Exhibits.</div>

      <div>&#160;</div>

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              <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Exhibit No.</span></div>
            </td>

    <td style="width: 2%; vertical-align: bottom;" colspan="1">&#160;</td>

    <td style="width: 88%; vertical-align: bottom;">
              <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Description</span></div>
            </td>

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  <tr>

    <td style="width: 10%; vertical-align: top;">
              <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="brhc10031559_ex99-1.htm">99.1</a></div>
            </td>

    <td style="width: 2%; vertical-align: top;" colspan="1">&#160;</td>

    <td style="width: 88%; vertical-align: top;">
              <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Press Release dated December 6, 2021.</div>
            </td>

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    <td style="width: 10%; vertical-align: top;" rowspan="1"><br />
            </td>

    <td style="width: 2%; vertical-align: top;" rowspan="1" colspan="1">&#160;</td>

    <td style="width: 88%; vertical-align: top;" rowspan="1">&#160;</td>

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    <td style="width: 10%; vertical-align: top;">
              <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104</div>
            </td>

    <td style="width: 2%; vertical-align: top;" colspan="1">&#160;</td>

    <td style="width: 88%; vertical-align: top;">
              <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cover Page Interactive Data File (embedded within the Inline XBRL document).</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-variant: small-caps; font-weight: bold;">SIGNATURE</div>

      <div>&#160;</div>

      <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be
        signed on its behalf by the undersigned, thereunto duly authorized.</div>

      <div>&#160;</div>

      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">


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    <td style="width: 50%; vertical-align: top;">&#160;</td>

    <td style="vertical-align: top;" colspan="2">
              <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
            </td>

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    <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>

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    <td style="width: 50%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated:&#160; December 7, 2021</div>
            </td>

    <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">By:</div>
            </td>

    <td style="width: 46%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ Patrick R. O&#8217;Neil</div>
            </td>

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    <td style="width: 50%; vertical-align: top;">&#160;</td>

    <td style="width: 4%; vertical-align: top;">&#160;</td>

    <td style="width: 46%; vertical-align: top;">
              <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-variant: small-caps; font-weight: bold;">Patrick R. O&#8217;Neil</div>
            </td>

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    <td style="width: 50%; vertical-align: top;">&#160;</td>

    <td style="width: 4%; vertical-align: top;">&#160;</td>

    <td style="width: 46%; vertical-align: top;">
              <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Legal Officer and General Counsel</div>
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<DOCUMENT>
<TYPE>EX-99.1
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<FILENAME>brhc10031559_ex99-1.htm
<DESCRIPTION>EXHIBIT 99.1
<TEXT>
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    <div style="text-align: right;"><font style="font-weight: bold;"> Exhibit 99.1</font><br>
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      <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 10pt; font-weight: bold;">Ionis and AstraZeneca to develop and commercialize eplontersen</div>
      <div><br>
      </div>
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            <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8722;</td>
            <td style="width: auto; vertical-align: top; text-align: left;">
              <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Collaboration expected to enable faster and deeper market penetration into growing global TTR amyloidosis market</div>
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            <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8722;</td>
            <td style="width: auto; vertical-align: top; text-align: left;">
              <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">The companies will jointly develop and commercialize eplontersen in the U.S., AstraZeneca has exclusive rights to commercialize in rest of the
                world</div>
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            <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8722;</td>
            <td style="width: auto; vertical-align: top; text-align: left;">
              <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bolsters Ionis&#8217; commercial organization as it prepares for multiple product launches</div>
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            <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8722;</td>
            <td style="width: auto; vertical-align: top; text-align: left;">
              <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis to hold webcast Dec. 7, 2021, at 10 a.m. Eastern Time</div>
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      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CARLSBAD, Calif., Dec. 6, 2021</font> &#8211; Ionis
        Pharmaceuticals, Inc. (NASDAQ: IONS), the leader in RNA-targeted therapies, today announced it has entered into a strategic collaboration agreement with AstraZeneca to develop and commercialize eplontersen, Ionis&#8217; investigational antisense medicine
        for the treatment of transthyretin amyloidosis (ATTR).</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen, formerly known as IONIS-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx, </sub>is designed to reduce the production of transthyretin, or TTR protein, to treat ATTR, a systemic,
        progressive and fatal disease. It uses Ionis&#8217; advanced <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">LI</font>gand-<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">C</font>onjugated <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">A</font>ntisense (LICA) technology.</div>
      <div><br>
      </div>
      <div>
        <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The companies will develop a global strategy for developing, manufacturing and commercializing eplontersen. A breakdown of responsibilities of the
          collaboration includes, but is not limited to:</div>
        <div><br>
        </div>
      </div>
      <div>
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              <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis will continue to lead the conduct of the global Phase 3 clinical trials in patients with hereditary ATTR amyloidosis (hATTR) with polyneuropathy
                  (NEURO-TTRansform) and cardiomyopathy (CARDIO-TTRansform).</div>
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              </td>
              <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis will manufacture and supply eplontersen for the ongoing clinical trials and process qualifications. AstraZeneca will be responsible for commercial supply,
                  with transition timing to be agreed by both companies.</div>
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              <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis and AstraZeneca will have shared responsibility for medical affairs and commercial activities in the U.S.</div>
              </td>
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        </table>
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              <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</td>
              <td style="width: auto; vertical-align: top; text-align: left;">
                <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca will have an exclusive license for eplontersen outside the U.S. except certain countries in Latin America.</div>
              </td>
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;We believe that bringing together Ionis&#8217; industry-leading experience in RNA-targeted therapeutics and deep knowledge of the TTR amyloidosis market with
        AstraZeneca&#8217;s global scale and leadership in cardiovascular drug development and commercialization will enable faster and deeper market penetration for the benefit of patients,&#8221; said Brett P. Monia, Ph.D., chief executive officer of Ionis. &#8220;In
        addition to being the best strategy to maximize patient and shareholder value for eplontersen, this agreement also represents a key step in bolstering our commercial organization as we prepare to launch multiple products.&#8221;</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Hereditary ATTR amyloidosis (hATTR) with polyneuropathy is expected to be the first indication for which the companies will seek regulatory approval for
        eplontersen, with the potential to file a new drug application (NDA) with the U.S. Food and Drug Administration by the end of 2022.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, Ionis will receive a $200 million upfront payment, up to $485 million in development and approval milestones, and up to
        $2.9 billion in sales-related milestone payments. The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions. Ionis is also eligible to earn royalties in the range of low double-digit to
        mid-20s percentage depending on region.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The agreement is expected to become effective by the end of 2021, subject to the satisfaction of requirements of the Hart-Scott-Rodino Antitrust
        Improvements Act of 1976.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Webcast</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis will conduct a webcast on Dec. 7 at 10 a.m. Eastern Time to discuss this announcement and related activities. Interested parties may access the
        webcast here. A webcast replay will be available for a limited time at the same address.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">About eplontersen</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen (formerly known as IONIS-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>) is an investigational antisense medicine developed with Ionis&#8217; <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">LI</font>gand-<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">C</font>onjugated <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">A</font>ntisense (LICA) technology that is designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive, and fatal disease.
        In patients with ATTR, both the mutant and wild type (wt) TTR protein builds up as fibrils in tissues, such as the peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR
        fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death. Ionis is currently evaluating eplontersen
        through its CARDIO-TTRansform Phase 3 study for the treatment of patients with hereditary and wild-type cardiomyopathy (ATTR-CM) and its NEURO-TTRansform Phase 3 study for the treatment of patients with hereditary transthyretin-mediated amyloid
        polyneuropathy (hATTR-PN).</div>
      <div><br>
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      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">About TTR Amyloidosis (ATTR)</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ATTR amyloidosis is a systemic, progressive and fatal disease in which patients experience multiple overlapping clinical manifestations caused by the
        inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR
        amyloid deposits in these tissues and organs leads to organ failure and eventually death.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Polyneuropathy due to hATTR is caused by the accumulation of misfolded mutated TTR protein in the peripheral nerves. Patients with polyneuropathy due to
        hATTR experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor functions, such as walking. These patients also accumulate TTR in other major organs, which progressively compromise their function
        and eventually leading to death within five to fifteen years of disease onset.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ATTR cardiomyopathy is caused by the accumulation of misfolded TTR protein in the cardiac muscle. Patients experience ongoing debilitating heart damage
        resulting in progressive heart failure, which results in death within 3 to 5 years from disease onset. ATTR cardiomyopathy includes both the genetic and wild-type form of the disease.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Worldwide, there are an estimated 300,000 &#8211; 500,000<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1<font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,</font>2</sup>
        patients with ATTR.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">About Ionis Pharmaceuticals, Inc.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense
        technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading neurological and cardiometabolic franchises. Our scientific innovation began and continues with the knowledge that sick
        people depend on us, which fuels our vision of becoming one of the most successful biotechnology companies.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To learn more about Ionis visit <font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; color: #0563C1;"><u>www.ionispharma.com</u></font>
        and follow us on twitter @ionispharma.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Forward-looking Statements</div>
      <div><br>
      </div>
      <div>
        <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This press release includes forward-looking statements regarding Ionis&#8217; business and the therapeutic and commercial potential of Ionis' technologies,
          eplontersen and other products in development. Any statement describing Ionis&#8217; goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such
          statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and
          particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis&#8217;
          forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements.</div>
      </div>
      <br>
      <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 30%; color: #000000; text-align: left;">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;"> <br>
        </sup></div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> Mohamed-Salem L, et al. Prevalence of wild type ATTR assessed as myocardial uptake in bone scan in the elderly population. Int J Cardiol. 2018
        Nov 1;270:192-196. doi: 10.1016/j.ijcard.2018.06.006.</div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup> Cuscaden C, et al. Estimation of prevalence of transthyretin (ATTR) cardiac amyloidosis in an Australian subpopulation using bone scans with
        echocardiography and clinical correlation. J Nucl Cardiol. 2020 May 8. doi: 10.1007/s12350-020-02152-x.</div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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      <div>
        <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Although Ionis&#8217; forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors
          currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended
          December 31, 2020, and the most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of these and other documents are available from the Company.</div>
        <div><br>
        </div>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its
        subsidiaries.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Pharmaceuticals<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup> is a trademark of Ionis Pharmaceuticals, Inc.</div>
      <div><br>
      </div>
      <div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis Investor Contact: </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">760-603-2331</font></div>
      <div><br>
      </div>
      <div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Ionis Media Contact: </font><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">760-603-4679</font></div>
      <div><br>
      </div>
      <div><br>
      </div>
      <div>
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<DESCRIPTION>XBRL TAXONOMY EXTENSION SCHEMA
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<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
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  </link:labelLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>5
<FILENAME>ions-20211206_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
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<span style="display: none;">v3.21.2</span><table class="report" border="0" cellspacing="2" id="idm140499682069080">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Document and Entity Information<br></strong></div></th>
<th class="th"><div>Dec. 06, 2021</div></th>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentType', window );">Document Type</a></td>
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<td class="text">IONIS PHARMACEUTICALS, INC.<span></span>
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</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityAddressStateOrProvince', window );">Entity Address, State or Province</a></td>
<td class="text">CA<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CityAreaCode', window );">City Area Code</a></td>
<td class="text">760<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_LocalPhoneNumber', window );">Local Phone Number</a></td>
<td class="text">931-9200<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_WrittenCommunications', window );">Written Communications</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_SolicitingMaterial', window );">Soliciting Material</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_PreCommencementTenderOffer', window );">Pre-commencement Tender Offer</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_PreCommencementIssuerTenderOffer', window );">Pre-commencement Issuer Tender Offer</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_Security12bTitle', window );">Title of 12(b) Security</a></td>
<td class="text">Common Stock, $.001 Par Value<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AmendmentFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the XBRL content amends previously-filed or accepted submission.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AmendmentFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CityAreaCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Area code of city</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CityAreaCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CoverAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Cover page.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CoverAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentPeriodEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>For the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period.  The format of the date is YYYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentPeriodEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentType">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The type of document being provided (such as 10-K, 10-Q, 485BPOS, etc). The document type is limited to the same value as the supporting SEC submission type, or the word 'Other'.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentType</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:submissionTypeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressAddressLine1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Address Line 1 such as Attn, Building Name, Street Name</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressAddressLine1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressCityOrTown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the City or Town</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressCityOrTown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressPostalZipCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Code for the postal or zip code</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressPostalZipCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressStateOrProvince">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the state or province.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressStateOrProvince</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:stateOrProvinceItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCentralIndexKey">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>A unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCentralIndexKey</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:centralIndexKeyItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityEmergingGrowthCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityEmergingGrowthCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFileNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Commission file number. The field allows up to 17 characters. The prefix may contain 1-3 digits, the sequence number may contain 1-8 digits, the optional suffix may contain 1-4 characters, and the fields are separated with a hyphen.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFileNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fileNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityIncorporationStateCountryCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Two-character EDGAR code representing the state or country of incorporation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityIncorporationStateCountryCode</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarStateCountryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityRegistrantName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityRegistrantName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityTaxIdentificationNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityTaxIdentificationNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:employerIdItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_LocalPhoneNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Local phone number for entity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_LocalPhoneNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_PreCommencementIssuerTenderOffer">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 13e<br> -Subsection 4c<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_PreCommencementIssuerTenderOffer</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_PreCommencementTenderOffer">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 14d<br> -Subsection 2b<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_PreCommencementTenderOffer</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_Security12bTitle">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Title of a 12(b) registered security.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_Security12bTitle</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:securityTitleItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SecurityExchangeName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the Exchange on which a security is registered.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection d1-1<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SecurityExchangeName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarExchangeCodeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SolicitingMaterial">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as soliciting material pursuant to Rule 14a-12 under the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Section 14a<br> -Number 240<br> -Subsection 12<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SolicitingMaterial</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_TradingSymbol">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Trading symbol of an instrument as listed on an exchange.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_TradingSymbol</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:tradingSymbolItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_WrittenCommunications">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as written communications pursuant to Rule 425 under the Securities Act.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Securities Act<br> -Number 230<br> -Section 425<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_WrittenCommunications</td>
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<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
