<SEC-DOCUMENT>0001140361-22-003182.txt : 20220131
<SEC-HEADER>0001140361-22-003182.hdr.sgml : 20220131
<ACCEPTANCE-DATETIME>20220131073253
ACCESSION NUMBER:		0001140361-22-003182
CONFORMED SUBMISSION TYPE:	8-K
PUBLIC DOCUMENT COUNT:		15
CONFORMED PERIOD OF REPORT:	20220124
ITEM INFORMATION:		Termination of a Material Definitive Agreement
ITEM INFORMATION:		Financial Statements and Exhibits
FILED AS OF DATE:		20220131
DATE AS OF CHANGE:		20220131

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:		22571346

	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'; font-size: 14pt; font-weight: bold;">SECURITIES AND EXCHANGE COMMISSION</div>

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

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        <div style="text-align: left; font-family: 'Times New Roman'; 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 following
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      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div>

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      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div>

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              <div style="font-family: 'Times New Roman'; font-size: 10pt;">Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))</div>
            </td>

  </tr>


</table>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div>

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            </td>

    <td style="width: auto; vertical-align: top; text-align: left;">
              <div style="font-family: 'Times New Roman'; font-size: 10pt;">Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))</div>
            </td>

  </tr>


</table>
      <div>&#160;</div>

      <div style="text-align: left; color: rgb(0, 0, 0); font-family: 'Times New Roman'; font-size: 10pt;">Securities registered pursuant to Section 12(b) of the Act:</div>

      <div><br />
      </div>

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    <td style="width: 31.1%; vertical-align: top; border-bottom: #000000 2px solid;">
              <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman'; font-size: 10pt;">Title of each class</div>
            </td>

    <td style="width: 4.7%; vertical-align: top;">&#160;</td>

    <td style="width: 17.22%; vertical-align: top; border-bottom: #000000 2px solid;">
              <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman'; font-size: 10pt;">Trading symbol</div>
            </td>

    <td style="width: 4.57%; vertical-align: top;">&#160;</td>

    <td style="width: 42.41%; vertical-align: top; border-bottom: #000000 2px solid;">
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  </tr>

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    <td style="width: 4.7%; vertical-align: top;">&#160;</td>

    <td style="width: 17.22%; vertical-align: top;">
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            </td>

    <td style="width: 4.57%; vertical-align: top;">&#160;</td>

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</table>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"> <br />
      </div>

      <div style="text-align: justify; font-family: 'Times New Roman'; 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 style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"> <br />
      </div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">
        <a id="z_Hlk11148519"></a>
<table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;">


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    <td style="width: 90%; text-align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman';">Emerging growth company</span> </td>

    <td style="width: 10%;">
                <div style="text-align: right;"><ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_1e0f843d702e43a1a42d674888583e86" contextRef="c20220124to20220124" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric> <span style="font-size: 10pt; font-family: 'Times New Roman';"></span></div>
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</table>
      </div>

      <div style="text-align: right;"><br />
      </div>

      <div style="text-align: justify; font-family: 'Times New Roman'; 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. &#9744;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"> <br />
      </div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">
        <hr style="border: none; border-bottom: 4px solid black; border-top: 1px solid black; height: 10px; color: #ffffff; background-color: #ffffff; text-align: center; margin-left: auto; margin-right: auto;" /> </div>

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          <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" /></div>

      </div>

    </div>

    <div>
      <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


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    <td style="width: 54pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Item 1.02</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
              <div style="font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Termination of a Material Definitive Agreement.</div>
            </td>

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</table>
      <div>&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">On January 31, 2022, Ionis Pharmaceuticals, Inc. (the &#8220;<span style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Company</span>&#8221;)









        issued a press release announcing that the Company&#8217;s licensee, Pfizer Inc. (&#8220;<span style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Pfizer</span>&#8221;), is discontinuing the Pfizer-led clinical development
        program for vupanorsen, an investigational antisense therapy that was being evaluated for potential indications in cardiovascular (CV) risk reduction and severe hypertriglyceridemia (SHTG), and will return development rights to vupanorsen to the
        Company.</div>

      <div>&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; 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>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">The Company&#8217;s wholly owned subsidiary, Akcea Therapeutics, Inc., entered into a License Agreement with Pfizer for the development and commercialization of vupanorsen
        on October 4, 2019 (the &#8220;<span style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Agreement</span>&#8221;). Under the terms of the Agreement, we granted Pfizer an exclusive license, with the right to grant
        certain sublicenses, under our intellectual property to develop, manufacture, commercialize and otherwise exploit vupanorsen worldwide. The Agreement will terminate effective April 25, 2022.</div>

      <div>&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">The foregoing description of the Agreement is a summary only and is qualified in its entirety by reference to the terms of the Agreement, a copy of which was filed as
        <a href="https://www.sec.gov/Archives/edgar/data/1662524/000156459020008119/akca-ex1015_357.htm">Exhibit 10.15</a> to Akcea&#8217;s Annual Report on Form 10-K for the year ended December 31, 2019.</div>

      <div>&#160;</div>

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    <td style="width: 54pt; vertical-align: top; font-family: 'Times New Roman'; 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'; font-size: 10pt; font-weight: bold;">Financial Statements and Exhibits.</div>
            </td>

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</table>
      <div>&#160;</div>

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

      <div>&#160;</div>

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    <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Exhibit No.</span></div>
            </td>

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

  </tr>

  <tr>

    <td style="width: 12%; vertical-align: bottom;" rowspan="1">
              <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt;"><a href="brhc10033283_ex99-1.htm">99.1</a></div>
            </td>

    <td style="width: 88%; vertical-align: bottom;" rowspan="1">
              <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Press Release dated January 31, 2022.</div>
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      <div style="text-align: center; font-family: 'Times New Roman'; 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'; 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>

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                <div style="margin: 0px; font-family: 'Times New Roman'; font-size: 10pt; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.<br />
                </div>
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              <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Dated:&#160; January 31, 2022</div>
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              <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman';">&#160;/s/ Patrick R. O&#8217;Neil</span></div>
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              <div style="margin: 0px; font-family: 'Times New Roman'; font-size: 10pt; font-variant: small-caps; font-weight: bold;">Patrick R. O&#8217;Neil</div>
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<DOCUMENT>
<TYPE>EX-99.1
<SEQUENCE>2
<FILENAME>brhc10033283_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'; font-size: 10pt; font-weight: bold;">Pfizer and Ionis announce discontinuation of vupanorsen clinical development program</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">NEW YORK and CARLSBAD, Calif., Jan. 31, 2022</font>&#160;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">&#8212;&#160;</font><u>Pfizer Inc.</u>&#160;(NYSE: PFE) and <u>Ionis Pharmaceuticals, Inc.</u> (NASDAQ: IONS) today announced the discontinuation of the Pfizer-led clinical development program for vupanorsen
        (PF-07285557), an investigational antisense therapy that was being evaluated for potential indications in cardiovascular (CV) risk reduction and severe hypertriglyceridemia (SHTG).</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Pfizer made this decision after a thorough review of data from the global Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, 8-arm
        parallel-group study of vupanorsen in statin-treated participants with dyslipidemia &#8212; also known as <font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">T</font>a<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">R</font>geting <font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">A</font>NGPTL3 with an a<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">N</font>tiSense




        o<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">L</font>igonucleotide in <font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">A</font>dul<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">T</font>s with dyslipid<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">E</font>mia (TRANSLATE-TIMI 70). As previously announced, the study met its primary endpoint,
        achieving a statistically significant reduction in non-high density lipoprotein cholesterol (non-HDL-C), as well as statistically significant reductions in triglycerides (TG) and angiopoietin-like 3 (ANGPTL3). However, the magnitude of non-HDL-C
        and TG reduction observed did not support continuation of the clinical development program for CV risk reduction or SHTG. Vupanorsen was also associated with dose-dependent increases in liver fat, and higher doses were associated with elevations in
        the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).</div>
      <div>&#160;</div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; color: rgb(0, 0, 0);">Pfizer will return development rights to vupanorsen to Ionis, from which it licensed the investigational therapy in a worldwide exclusive <u><font style="font-size: 10pt; font-family: 'Times New Roman';">agreement</font></u> in November 2019.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">&#8220;While this outcome is disappointing, the clinical and scientific knowledge derived from the vupanorsen program will hopefully contribute to a greater understanding of
        cardiovascular risk reduction and severe hypertriglyceridemia and the current gaps in treating these conditions,&#8221; said James Rusnak, M.D., Ph.D., senior vice president and chief development officer, internal medicine and hospital, Pfizer. &#8220;Pfizer
        remains dedicated to research and development in the cardiovascular category and helping to address the unmet medical needs of patients with cardiovascular diseases. We are grateful to the patients, investigators and support staff who have
        participated in this important research program.&#8221;</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">&#8220;Although this is not the outcome we would have liked, we are grateful for this collaboration with Pfizer whose leadership in the development of vupanorsen has been
        instrumental in gaining important insights and learnings that will help us continue to deliver potentially life transforming treatments for people impacted by cardiovascular disease,&#8221; said Richard S. Geary, Ph.D., executive vice president and chief
        development officer at Ionis.</div>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"> <br>
        </font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">About vupanorsen<font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
          </font></font><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Vupanorsen is an investigational antisense therapy discovered by Ionis. Vupanorsen acts through&#160;a novel mechanism, targeting ANGPTL3, a genetically validated target of
        lipoprotein metabolism.<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup>&#160;Vupanorsen uses Ionis&#8217; advanced <font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">LI</font>gand <font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">C</font>onjugated




        <font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">A</font>ntisense (LICA) technology platform. The potential therapeutic benefits of ANGPTL3 reduction are supported by the discovery that people with a genetic
        deficiency in ANGPTL3 have reduced levels of LDL-C and TG, and a decreased risk of coronary artery disease.<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup>&#160;</div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">References</font><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
          </font><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup>Endocrine. 2016 Jan 11;52(2):187-193.<font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
          </font><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup>JAMA Cardiol. 2018 Oct 1;3(10):957-966.<font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
          </font></font><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">About Ionis Pharmaceuticals, Inc.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; 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'; font-size: 10pt;">To learn more about Ionis, visit www.ionispharma.com and follow us on Twitter @ionispharma.</div>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"> <br>
        </font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">About Pfizer: Breakthroughs that change patients&#8217; lives<font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
          </font></font><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for
        quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention,
        treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world&#8217;s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local
        communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on
        our website at&#160;<u>www.Pfizer.com</u>. In addition, to learn more, please visit us on&#160;<u>www.Pfizer.com</u>&#160;and follow us on Twitter at&#160;<u>@Pfizer</u>&#160;and&#160;<u>@PfizerNews</u>,&#160;<u>LinkedIn</u>,&#160;<u>YouTube</u>&#160;and like us on Facebook at&#160;<u>Facebook.com/Pfizer</u>.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Ionis&#8217; Forward-looking Statements</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">This press release includes forward-looking statements regarding Ionis&#8217; business and the therapeutic and commercial potential of Ionis&#8217; technologies, vupanorsen 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>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; 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&#8217; programs are described in additional detail in Ionis&#8217; annual report on Form 10-K for the year ended Dec. 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>
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      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">
        <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">In this press release, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals and its subsidiaries.</div>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Ionis Pharmaceuticals&#174; is a trademark of Ionis Pharmaceuticals, Inc.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Pfizer disclosure notice</div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
        </font>The information contained in this release is as of January 27, 2022. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">This release contains forward-looking information about Pfizer&#8217;s research and development in the cardiovascular category, including its potential benefits, that involves
        substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and
        development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of
        unfavorable new clinical &#160;data and further analyses of existing clinical &#160;data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied
        with the design of and results from our clinical studies; whether and when drug applications may be filed in any jurisdictions for any potential product candidates; whether and when any such applications may be approved by regulatory authorities,
        which will depend on myriad factors, including making a determination as to whether the product&#8217;s benefits outweigh its known risks and determination of the product&#8217;s efficacy and, if approved, whether any such product candidates will be
        commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of any such product candidates; the impact of COVID-19
        on Pfizer&#8217;s business, operations and financial results; and competitive developments.</div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
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      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"> A further description of risks and uncertainties can be found in Pfizer&#8217;s Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and in its subsequent
        reports on Form 10-Q, including in the sections thereof captioned &#8220;Risk Factors&#8221; and &#8220;Forward-Looking Information and Factors That May Affect Future Results&#8221;, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S.
        Securities and Exchange Commission and available at&#160;<u>www.sec.gov</u>&#160;and&#160;<u>www.pfizer.com</u>.</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Ionis Investor Contact:</div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">760-603-2331</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Ionis Media Contact:</div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">760-603-4679</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Pfizer Media Contact:</font><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
        </font><u>PfizerMediaRelations@pfizer.com</u><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
        </font>212-733-1226</div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Pfizer Investor Contact:</font><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
        </font><u>IR@pfizer.com</u><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
        </font>212-733-4848</div>
      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
        </font>###</div>
      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
      </div>
      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
      </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:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021/dei-2021.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
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  </link:labelLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>5
<FILENAME>ions-20220124_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 8.0.0.0 Broadridge-->
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<FILENAME>R1.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.0.1</span><table class="report" border="0" cellspacing="2" id="idm140010981038248">
<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>Jan. 24, 2022</div></th>
</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_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
<td class="text">&#160;<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_DocumentType', window );">Document Type</a></td>
<td class="text">8-K<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_AmendmentFlag', window );">Amendment Flag</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_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Jan. 24,  2022<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_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">IONIS PHARMACEUTICALS, INC.<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_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">&#8220;IONS&#8221;<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>
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<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>
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<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>
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<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>
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<td style="white-space:nowrap;">dei_EntityFileNumber</td>
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<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">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityIncorporationStateCountryCode</td>
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<td><strong> Balance Type:</strong></td>
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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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
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<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">
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<td><strong> Name:</strong></td>
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<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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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>
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<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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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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>
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<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>
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<td style="white-space:nowrap;">dei_SolicitingMaterial</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<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">
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<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
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<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>
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 "std_ref": {
  "r0": {
   "Name": "Exchange Act",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "b"
  },
  "r1": {
   "Name": "Exchange Act",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "d1-1"
  },
  "r2": {
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   "Number": "240",
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   "Section": "13e",
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  },
  "r3": {
   "Name": "Exchange Act",
   "Number": "240",
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  "r4": {
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   "Number": "240",
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  },
  "r5": {
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   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "b-2"
  },
  "r6": {
   "Name": "Securities Act",
   "Number": "230",
   "Publisher": "SEC",
   "Section": "425"
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 },
 "version": "2.1"
}
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
