Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 1 of 52
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`UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF NEW YORK
`
`NOVARTIS PHARMA AG, NOVARTIS
`PHARMACEUTICALS CORPORATION,
`and
`NOVARTIS TECHNOLOGY LLC,
`
`Plaintiffs,
`
`v.
`
`REGENERON PHARMACEUTICALS,
`INC.,
`
`Defendant.
`
`Civil Action No.: 1:20-cv-00690 (TJM-CFH)
`
`JURY TRIAL DEMANDED
`
`REGENERON PHARMACEUTICALS, INC.’S PARTIAL ANSWER TO
`NOVARTIS’S COMPLAINT FOR PATENT INFRINGEMENT,
`AFFIRMATIVE DEFENSES, AND COUNTERCLAIM
`
`Defendant Regeneron Pharmaceuticals, Inc. (“Regeneron” or “Defendant”), by and
`
`through its attorneys, Barclay Damon LLP and Weil, Gotshal & Manges LLP, as and for its Partial
`
`Answer1, Affirmative Defenses, and Counterclaim to the Complaint for Patent Infringement (the
`
`“Complaint”) of plaintiff Novartis Pharma AG, Novartis Pharmaceuticals Corporation, and
`
`Novartis Technology LLC (collectively, “Plaintiffs” or “Novartis”), state as follows:
`
`1.
`
`Regeneron admits Wet age-related macular degeneration (“Wet AMD”) is the
`
`leading cause of vision loss in individuals over 50, drugs called vascular endothelial growth factor
`
`(“VEGF”)-antagonists can be used to treat Wet AMD and other devastating ophthalmic conditions,
`
`1 Regeneron has filed a motion to dismiss concurrently with this Partial Answer directed to the
`allegations of paragraphs 33 and 34 of the Complaint, and has therefore not responded to those
`allegations in this Answer.
`
`1
`
`Novartis Exhibit 2006.001
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 2 of 52
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`but must be injected into the eye by a physician, and that the injection itself carries a risk of
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`complications including infection, inflammation, introduction of particles into the eye, and even
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`potentially blindness. Regeneron denies the remaining allegations contained in paragraph 1 of the
`
`Complaint.
`
`2.
`
`Regeneron admits it manufactures and markets in the United States a product called
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`EYLEA® (“EYLEA”), which is provided in vial and pre-filled syringe (“PFS”) presentations
`
`(“EYLEA PFS”), both of which contain the VEGF-antagonist aflibercept. Regeneron denies the
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`remaining allegations contained in paragraph 2 of the Complaint.
`
`3.
`
`Regeneron denies knowledge or information sufficient to form a belief as to the
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`truth or falsity of the allegations contained in paragraph # of the Complaint, and therefore, denies
`
`them.
`
`4.
`
`Regeneron denies knowledge or information sufficient to form a belief as to the
`
`truth or falsity of the allegations contained in paragraph 4 of the Complaint, and therefore, denies
`
`them.
`
`5.
`
`Regeneron denies knowledge or information sufficient to form a belief as to the
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`truth or falsity of the allegations contained in paragraph 5 of the Complaint, and therefore, denies
`
`them.
`
`6.
`
`7.
`
`8.
`
`Regeneron admits the allegations contained in paragraph 6 of the Complaint.
`
`Regeneron admits the allegations contained in paragraph 7 of the Complaint.
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`Regeneron admits that the Complaint alleges a cause of action for patent
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`infringement under 35 U.S.C. § 271, but denies the remaining allegations contained in paragraph
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`8 of the Complaint.
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`9.
`
`Regeneron admits the allegations contained in paragraph 9 of the Complaint.
`
`
`
`2
`
`Novartis Exhibit 2006.002
`Regeneron v. Novartis, IPR2021-00816
`
`

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`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 3 of 52
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`10.
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`11.
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`Regeneron admits the allegations contained in paragraph 10 of the Complaint.
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`Regeneron admits it has a facility at 81 Columbia Turnpike, Rensselaer, New York
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`12144 and admits that venue is proper in this District. Regeneron denies the remaining allegations
`
`contained in paragraph 11 of the Complaint.
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`12.
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`Regeneron admits that on December 29, 2015, the United States Patent and
`
`Trademark Office issued the ’631 Patent2, entitled “Syringe,” and that the patent lists as inventors
`
`Juergen Sigg, Christophe Royer, Andrew M. Bryant, Heinrich M. Buettgen, and Marie Picci.
`
`Regeneron admits that what appears to be a true and correct copy of the ʼ631 Patent is attached as
`
`Exhibit A to the Complaint. Regeneron denies the remaining allegations contained in paragraph
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`12 of the Complaint.
`
`13.
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`Regeneron admits that 35 U.S.C. § 282 states that a patent shall be presumed valid.
`
`Regeneron denies the remaining allegations contained in paragraph 13 of the Complaint.
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`14.
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`Regeneron denies knowledge or information sufficient to form a belief as to the
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`truth or falsity of the allegations contained in paragraph 14 of the Complaint, and therefore, denies
`
`them.
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`15.
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`Regeneron admits Claim 1 of the ’631 Patent reads as follows:
`
`1.
`
`A pre-filled, terminally sterilized syringe for intravitreal injection, the
`syringe comprising a glass body forming a barrel, a stopper and a plunger
`and containing an ophthalmic solution which comprises a VEGF-
`antagonist, wherein:
`
`(a) the syringe has a nominal maximum fill volume of between about 0.5
`ml and about 1 ml,
`
`(b) the syringe barrel comprises from about 1 μg to 100 [μ]g silicone oil,
`
`
`2
`The “’631 patent” refers to U.S. Patent No. 9,220,631.
`3
`
`
`
`Novartis Exhibit 2006.003
`Regeneron v. Novartis, IPR2021-00816
`
`

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`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 4 of 52
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`(c) the VEGF antagonist solution comprises no more than 2 particles > 50
`μm in diameter per ml and wherein the syringe has a stopper break loose
`force of less than about 11N.
`
`Regeneron denies the remaining allegations contained in paragraph 15 of the
`
`Complaint.
`
`16.
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`Regeneron admits EYLEA PFS is a syringe pre-filled with the VEGF-antagonist
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`aflibercept and approved for the treatment of, among other things, Wet AMD. Regeneron denies
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`the remaining allegations contained in paragraph 16 of the Complaint.
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`17.
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`Regeneron realleges and incorporates by reference its responses in the preceding
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`paragraphs as though fully stated herein.
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`18.
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`Regeneron denies that EYLEA PFS satisfies each and every element, either literally
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`or under the doctrine of equivalents, of one or more claims of the ’631 Patent and otherwise denies
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`the allegations of paragraph 18.
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`19.
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`Regeneron admits that EYLEA PFS is a pre-filled, terminally sterilized syringe for
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`intravitreal injection.
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`20.
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`Regeneron denies that the EYLEA PFS syringe comprises a glass body forming a
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`barrel, a stopper, and a plunger to the extent Novartis maintains its assertion that the plunger and
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`stopper of claim 1 of the ’631 Patent requires a particular design that limits movement of the
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`stopper and prevents ingress of gasses during sterilization, as Novartis asserted in International
`
`Trade Commission Investigation No. 337-TA-1207.
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`21.
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`Regeneron admits that the EYLEA PFS contains an ophthalmic solution which
`
`comprises a VEGF-antagonist. Regeneron admits the drug product in the EYLEA PFS is a solution
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`of the VEGF antagonist aflibercept provided at a strength of 40 mg/mL, and the approved
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`indications for EYLEA PFS are ophthalmic.
`
`4
`
`
`
`Novartis Exhibit 2006.004
`Regeneron v. Novartis, IPR2021-00816
`
`

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`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 5 of 52
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`22.
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`Regeneron admits that the EYLEA PFS has a nominal maximum fill volume of
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`between about 0.5 ml and about 1 ml.
`
`23.
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`Regeneron denies that the EYLEA PFS barrel comprises about 1 μg to 100 μg
`
`silicone oil to the extent Novartis maintains its assertion that silicone oil quantities measured via
`
`certain methods are not within the scope of claim 1 of the’631 Patent, as Novartis asserted in
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`International Trade Commission Investigation No. 337-TA-1207.
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`24.
`
`Regeneron admits that the VEGF antagonist solution in the EYLEA PFS comprises
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`no more than 2 particles >50 μm in diameter per ml.
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`25.
`
`Regeneron admits that, to the extent this claim limitation is not indefinite, the
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`EYLEA PFS can have a stopper break loose force of less than 11N depending on the test conditions
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`at which the stopper break loose force is measured. Regeneron otherwise denies the allegations in
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`this paragraph.
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`26.
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`Regeneron admits that the EYLEA PFS is presented in one blister pack containing
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`one EYLEA 2 mg/0.05 mL sterile, single-dose pre-filled glass syringe.
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`27.
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`Regeneron admits that the VEGF-antagonist aflibercept in the EYLEA PFS is
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`administered by intravitreal injection.
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`28.
`
`Regeneron denies that it has made, used, offered for sale, sold, and or imported,
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`and continues to make, use, offer for sale, sell, and/or import, the infringing EYLEA PFS product
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`in the United States to the extent the EYLEA PFS does not infringe the ’631 Patent as described
`
`above in paragraphs 18-27.
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`29.
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`Regeneron denies that it has actively encouraged infringement of at least claim 24
`
`of the ’631 Patent by providing physicians with instructions to administer EYLEA PFS to treat
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`patients suffering from choroidal neovascularization, wet age-related macular degeneration,
`
`
`
`5
`
`Novartis Exhibit 2006.005
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 6 of 52
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`macular edema secondary to retinal vein occlusion, choroidal neovascularization secondary to
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`pathologic myopia, diabetic macular edema, diabetic retinopathy, and/or proliferative retinopathy
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`to the extent the EYLEA PFS does not infringe the ’631 Patent as described above in paragraphs
`
`18-27. Regeneron denies knowledge or information sufficient to form a belief as to the truth or
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`falsity of the remaining allegations contained in paragraph 29 of the Complaint, and therefore,
`
`denies them.
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`30.
`
`Regeneron denies that it has actively induced infringement of one or more claims
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`of the ’631 Patent, either literally or under the doctrine of equivalents, in violation of 35 U.S.C.
`
`§ 271(b) to the extent the EYLEA PFS does not infringe the ’631 Patent as described above in
`
`paragraphs 18-27.
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`31.
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`Regeneron denies that it has engaged in unlawful infringement activities that have
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`caused and will continue to cause Novartis substantial harm.
`
`32.
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`33.
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`Regeneron denies the allegations contained in paragraph 32 of the Complaint.
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`In lieu of responding to the allegations in paragraph 33, Regeneron has filed a
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`motion to dismiss concurrently with this Partial Answer directed to the allegations of this
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`paragraph.
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`34.
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`In lieu of responding to the allegations in paragraph 34, Regeneron has filed a
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`motion to dismiss concurrently with this Partial Answer directed to the allegations of this
`
`paragraph.
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`PRAYER FOR RELIEF
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`Regeneron denies that Novartis is entitled to any of the relief sought in the Prayer for Relief
`
`set forth in the Complaint.
`
`
`
`6
`
`Novartis Exhibit 2006.006
`Regeneron v. Novartis, IPR2021-00816
`
`

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`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 7 of 52
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`DEFENSES
`
`Regeneron asserts the following defenses to Novartis’s claims without admitting or
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`acknowledging that it bears the burden of proof as to any of the defenses asserted. Regeneron
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`reserves the right to amend its Partial Answer to add additional defenses.
`
`INTRODUCTION
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`Regeneron’s EYLEA® (aflibercept) injection is an innovative biologic drug for the
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`treatment of a variety of severe eye diseases.
`
`Regeneron’s EYLEA and Novartis’s LUCENTIS and BEOVU are drugs that treat certain
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`eye diseases involving overproduction of a naturally occurring protein in the body called vascular
`
`endothelial growth factor (“VEGF”). This VEGF overproduction can cause vision loss and even
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`blindness, and many millions of patients suffer from VEGF-related eye diseases.
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`As “anti-VEGF” drugs, EYLEA, LUCENTIS, and BEOVU must be injected with regular
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`frequency into a patient’s eye. The frequency, manner, and safety of injection are important factors
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`in the success of treatment, and the method of administration is therefore significant. In that regard,
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`EYLEA and LUCENTIS were historically sold only in vial form and ultimately loaded into a
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`separate needle or syringe for injection. Recently, however, the market for anti-VEGFs has
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`converted from vial to PFS, which is a more accurate and more convenient method of
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`administration that carries a lower risk of introducing foreign particles into the eye, which can
`
`cause severe complications such as endophthalmitis. LUCENTIS and EYLEA are effectively the
`
`only two approved anti-VEGF PFS prescribed in the United States.3
`
`
`3
`While Macugen received FDA approval in 2004 for a prefilled syringe to treat one VEGF-
`related eye disease, it is also an older, less effective treatment that is rarely prescribed anymore, if
`at all.
`
`
`
`7
`
`Novartis Exhibit 2006.007
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 8 of 52
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`There are numerous challenges associated with commercializing a PFS with a complex
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`biologic drug such as EYLEA or LUCENTIS. For example, there are a limited number of
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`companies that can fill the syringe with the drug in accordance with the required sterile conditions,
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`and the existing “fillers” have limited capacity. Vetter Pharma International GmbH (“Vetter”) is
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`the leading PFS filler and is the exclusive PFS filler for Novartis’s LUCENTIS PFS. Regeneron
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`and Vetter also have had a long-standing relationship. For many years, Vetter has provided non-
`
`exclusive filling services to Regeneron for EYLEA in vial form. Starting in 2005, Regeneron and
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`Vetter also embarked on a collaboration to commercialize an EYLEA PFS. This successful
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`collaboration led to regulatory approval for EYLEA PFS in Australia in 2012.
`
`Unbeknownst to Regeneron, however, as Regeneron and Vetter were jointly working to
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`commercialize an EYLEA PFS, Novartis was pursuing its own mission in 2013 to fraudulently
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`procure a United States patent claiming a PFS containing any anti-VEGF drug, including EYLEA.
`
`Given that the prior art already described and disclosed such a PFS, Novartis could secure its patent
`
`only by ensuring that the U.S. Patent and Trademark Office (“USPTO”) was not aware of that
`
`prior art. And Novartis did just that. By deliberately withholding material prior art from the
`
`USPTO, Novartis succeeded in obtaining the patent asserted in this case—the ’631 Patent—
`
`broadly claiming a PFS with any anti-VEGF, including EYLEA.4 As pled in detail below, specific
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`Novartis employees involved in the prosecution of the ’631 Patent knew of the omitted prior art
`
`and also knew the omitted prior art was material, for example because of multiple decisions by a
`
`set of USPTO examiners in a separate patent application covering overlapping subject matter that
`
`Novartis ultimately abandoned. In order to gain allowance of the ’631 Patent, the Novartis
`
`
`4
`The ’631 Patent specifically identifies EYLEA and states that “[a]flibercept is the preferred
`nonantibody VEGF antagonist for use with the invention.” ’631 Patent at Col. 6, ll. 42-43.
`8
`
`
`
`Novartis Exhibit 2006.008
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 9 of 52
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`employees made a deliberate decision to withhold the prior art from the different USPTO examiner
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`that was reviewing the application for the ’631 Patent, and made this decision with an intent to
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`deceive the USPTO into allowing the claims of the ʼ631 Patent to issue.
`
`The ’631 Patent is additionally and independently unenforceable because Novartis
`
`employees, as set forth in detail below, deliberately withheld material information from the
`
`USPTO showing that at least one Vetter employee should have been named as an inventor of
`
`the ’631 Patent. The Novartis employees knew
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` The
`
`-
`
`Novartis patent family
`
` includes U.S. Patent Application No. 13/750,032, which was
`
`issued by the USPTO on December 29, 2015, as the ’631 Patent. Novartis and Vetter also knew
`
`that 35 U.S.C. § 116 requires that when a claimed invention is made by two or more persons jointly,
`
`they must apply for a patent jointly, and each inventor must submit the required oath of
`
`inventorship to the USPTO. Novartis and Vetter also knew, consistent with § 116, that USPTO
`
`regulations require each individual who is a joint inventor of a claimed invention to execute and
`
`submit an oath or declaration identifying that individual as a joint inventor. 37 C.F.R. § 1.63. The
`
`
`
`9
`
`Novartis Exhibit 2006.009
`Regeneron v. Novartis, IPR2021-00816
`
`

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`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 10 of 52
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`consequence of failing to comply with this regulation is that a patent cannot be issued if the named
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`inventors did not invent all of the subject matter sought to be patented under 35 U.S.C. § 102(f).5
`
`FIRST AFFIRMATIVE DEFENSE
`(Failure to State a Claim)
`
`The Complaint fails to state a claim upon which relief can be granted.
`
`SECOND AFFIRMATIVE DEFENSE
`(Invalidity)
`
`As set forth in detail below, the claims of the ’631 Patent are invalid and/or unenforceable
`
`for failure to comply with one or more of the requirements set forth in Title 35 of the United States
`
`Code, including, but not limited to, Sections 102, 103, and/or 112.
`
`All asserted claims of the ’631 Patent are invalid under § 102 and/or § 103 in view of the
`
`prior art.
`
`As a non-limiting example, claims 1-24 of the ’631 Patent are invalid as obvious under 35
`
`U.S.C. § 103 based on WO 2011/006877 (“Sigg”) in view of WO 2009/030976 (“Boulange”), and
`
`if necessary, USP Chapter <789> (“USP789”). As a further example, claims 1-24 are invalid as
`
`obvious under 35 U.S.C § 103 based on WO 2008/077155 (“Lam”) in view of Boulange, and if
`
`necessary, USP789; and the prior art Macugen pre-filled syringe (“Macugen PFS”) in view of
`
`Boulange, and if necessary, USP789. Additionally, claim 25 is invalid as obvious under 35 U.S.C
`
`§ 103 based on any of the above combinations and the prior art Macugen Label (“Macugen®
`
`Label”); and claim 26 is invalid as obvious under 35 U.S.C § 103 based on any of the above
`
`combinations and James A. Dixon, et al. “VEGF Trap-Eye for the treatment of neovascular age-
`
`related macular degeneration.” Expert opinion on investigational drugs 18.10 (2009): 1573-1580.
`
`
`5
`35 U.S.C. § 102(f) states that “a person shall be entitled to a patent unless…he did not
`himself invent the subject matter sought to be patented.”
`10
`
`
`
`Novartis Exhibit 2006.0010
`Regeneron v. Novartis, IPR2021-00816
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`

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`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 11 of 52
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`(“Dixon”). For example, all the claims of the ’631 Patent are invalid under 35 U.S.C § 103 for at
`
`least the reasons set forth in Regeneron’s three IPR petitions (IPR2020-01317, IPR2020-01318,
`
`and IPR2021-00816), which are incorporated here in full.
`
`All the claims of the ’631 Patent are invalid under 35 U.S.C § 102(g) to the extent that
`
`Regeneron employees had already conceived and reduced to practice the subject matter claimed
`
`in the ’631 Patent.
`
`Regeneron reserves the right to rely on additional prior art for the purpose of this
`
`affirmative defense insofar as it identifies such art during the course of this case.
`
`All asserted claims of the ’631 Patent are invalid under § 112 for failure to provide an
`
`adequate written description or enabling disclosure, or for indefiniteness. As a nonlimiting
`
`example, the ’631 Patent fails to sufficiently describe or enable any process to achieve the claimed
`
`amounts of silicone oil and forces, and likewise fails to sufficiently describe or enable any process
`
`for the claimed terminal sterilization. As a further nonlimiting example, ’631 Patent fails to
`
`sufficiently describe or enable the full scope of the claimed “VEGF-antagonist,” “anti-VEGF
`
`antibody,” and “non-antibody VEGF antagonist” genus. As a further nonlimiting example, all
`
`asserted claims of the ’631 Patent are indefinite because the term “about” does not provide
`
`objective boundaries to the claimed ranges and the claims fail to identify the conditions at which
`
`the claimed break loose and slide forces are to be measured. Regeneron reserves the right to rely
`
`on additional arguments to show that all asserted claims of the ’631 Patent are invalid under § 112
`
`for failure to provide an adequate written description or enabling disclosure, or for indefiniteness
`
`insofar as it identifies them during the course of this case.
`
`Based on the foregoing reasons, Regeneron denies in its Partial Answer that the claims of
`
`the ’631 Patent are valid.
`
`
`
`11
`
`Novartis Exhibit 2006.0011
`Regeneron v. Novartis, IPR2021-00816
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`

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`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 12 of 52
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`THIRD AFFIRMATIVE DEFENSE
`(Non-infringement)
`
`Regeneron does not directly infringe, indirectly infringe, contribute to the infringement, or
`
`induce infringement of any valid or enforceable claim of the ’631 Patent, either literally or under
`
`the doctrine of equivalents, and has not otherwise committed any acts in violation of 35 U.S.C. §
`
`271 to the extent the EYLEA PFS does not infringe the ’631 Patent as described above in
`
`paragraphs 18-27 above. Regeneron has not manufactured, imported, sold for importation, or sold
`
`within the United States after importation, any product that is covered by any valid and enforceable
`
`claim of the ’631 Patent in this case.
`
`FOURTH AFFIRMATIVE DEFENSE
`(No Inducement)
`
`Regeneron has not actively induced the alleged infringement of any valid or enforceable
`
`claim of the ’631 Patent and lacks any specific intent to induce infringement to the extent the
`
`EYLEA PFS does not infringe the ’631 Patent as described above in paragraphs 18-27 above.
`
`FIFTH AFFIRMATIVE DEFENSE
`(Injunctive Relief)
`
`Novartis’s claim for injunctive relief is barred because there exists an adequate remedy at
`
`law and Novartis’s claims otherwise fail to meet the requirements for such relief. Further, the
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`public interest would be disserved by such relief, as it would adversely affect the public health and
`
`welfare, competitive conditions in the United States economy, and/or United States consumers.
`
`For example, the ITC Staff, an independent arm of the government tasked with representing the
`
`public interest in ITC investigations, concluded that the exclusion of the Eylea PFS from the United
`
`States would be contrary to the public interest.
`
`
`
`12
`
`Novartis Exhibit 2006.0012
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 13 of 52
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`SIXTH AFFIRMATIVE DEFENSE
`(Unenforceability Due To Inequitable Conduct)
`
`As set forth in detail below, the ’631 Patent is unenforceable due to the inequitable conduct
`
`on the part of Novartis personnel, including but not limited to the named inventors and prosecuting
`
`attorneys, in obtaining the patent. Specifically, on information and belief, these individuals
`
`withheld material prior art during the prosecution of the patent with the intent to deceive, and
`
`improperly omitted additional inventors from the patent, with the intent to deceive. These acts
`
`render the ’631 Patent unenforceable.
`
`BACKGROUND
`
`Novartis alleges in its Complaint that it is the assignee of the ’631 Patent, entitled “Syringe.”
`
`The ’631 Patent issued on December 29, 2015, and it was assigned to Novartis AG. In February
`
`2020, ownership of the ’631 Patent was transferred to Novartis Technology LLC, Novartis
`
`Pharmaceuticals Corporation, and Novartis Pharma AG, the three Novartis plaintiffs. The ’631
`
`Patent term extends until 2033. Novartis further alleges that, as the assignee of the ’631 Patent, it
`
`owns the entire right, title, and interest in the ’631 Patent. A copy of the ’631 Patent is attached to
`
`the Complaint as Exhibit A.
`
`In their Complaint, Novartis alleges that Regeneron’s EYLEA PFS infringes at least one
`
`claim of the ’631 Patent.
`
`
`
`
`
`
`
`13
`
`Novartis Exhibit 2006.0013
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 14 of 52
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`Independent claim 1 of the ’631 Patent is reproduced below.
`
`1. A pre-filled, terminally sterilized syringe for intravitreal
`injection, the syringe comprising a glass body forming a
`barrel, a stopper and a plunger and containing an ophthalmic
`solution which comprises a VEGF-antagonist, wherein:
`(a) the syringe has a nominal maximum fill volume of
`between about 0.5 ml and about 1 ml,
`(b) the syringe barrel comprises from about 1 µg to 100 ug
`silicone oil,
`( c) the VEGF antagonist solution comprises no more than
`2 particles >50 µmin diameter per ml and wherein the
`syringe has a stopper break loose force ofless than a bout
`llN.
`
`
`
`The ’631 Patent is unenforceable due to the inequitable conduct of at least Juergen Sigg, a
`
`Novartis employee and the lead inventor of the ’631 Patent, and at least Andrew Holmes and Jim
`
`Lynch, who were the primary patent practitioners at Novartis responsible for the prosecution of
`
`the application that led to the issuance of the ’631 Patent. Juergen Sigg, Andrew Holmes, and Jim
`
`Lynch, who were all subject to a continuing duty to disclose information material to patentability,
`
`deliberately withheld prior art disclosing terminal sterilization of a prefilled syringe containing a
`
`VEGF antagonist, which the individuals knew was material to the patentability of claims of
`
`the ’631 Patent. As detailed below, the claims of the ’631 Patent would not have been allowed had
`
`the examiner conducting the examination of application for the ’631 Patent been aware of the
`
`undisclosed prior art. At least Juergen Sigg, Andrew Holmes, and Jim Lynch knew of the
`
`materiality of this prior art based on office actions by a different set of examiners during
`
`prosecution of a parallel patent family, but deliberately withheld the information demonstrating
`
`unpatentability from the examiner that was conducting the examination of the application for
`
`the ’631 Patent. The single most reasonable inference that may be drawn from the evidence
`
`
`
`14
`
`Novartis Exhibit 2006.0014
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 15 of 52
`
`described below is that the Juergen Sigg, Andrew Holmes, and Jim Lynch withheld this material
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`prior art with an intent to deceive the USPTO.
`
`Because patents affect the public interest and patent examinations are conducted ex parte,
`
`the USPTO and courts impose a duty of candor and disclosure upon inventors (such as Juergen
`
`Sigg), patent applicants, and their representatives before the USPTO (e.g., registered patent
`
`attorneys and agents such as Andrew Holmes and Jim Lynch). As part of this duty, the USPTO
`
`requires inventors, patent applicants and their representatives to disclose to the examiner—through
`
`the Information Disclosure Statement (“IDS”)—all “information known to that individual to be
`
`material to patentability.” See 37 C.F.R. § 1.56. This duty of candor includes the duty to
`
`supplement the IDS with any material information or references the inventors, applicants or their
`
`representatives become aware of after the initial filing of the patent application up to and including
`
`the date of issuance of the patent.
`
`The Prosecution of U.S. Patent Application No. 13/750,352 That Ultimately Issued as the
`’631 Patent
`The application for the ’631 Patent (App. No. 13/750,352) (“the ’352 Application”) was
`
`filed on January 25, 2013. The application data sheet was signed by Andrew Holmes, Juergen Sigg,
`
`and other Novartis employees, but not any of the Vetter individual(s) who contributed to the
`
`claimed inventions. Novartis employees also submitted an inventor declaration pursuant to 37
`
`C.F.R. § 1.63 – but again with no Vetter individuals. The ’352 Application included one
`
`independent claim and thirty-one dependent claims directed to a prefilled syringe, blister packs
`
`comprising a prefilled syringe and a method of treating a patient using the prefilled syringe. As
`
`shown below, originally filed claim 1 was directed to structural aspects of the prefilled syringe,
`
`the fill volume of the syringe, the dosage volume of the VEGF antagonist solution, the amount of
`
`silicone oil on the syringe barrel, and the number of particles in the VEGF antagonist solution.
`
`
`
`15
`
`Novartis Exhibit 2006.0015
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 16 of 52
`
`l.
`
`A pre-filled S)'Tinge. the syringe comprising a glass body, a stopper and a plunger, the
`
`body comprising an cutlet al an outlet end and the stopper being arranged within \he lx)dy such
`that a front surface of the stopper and the body define a variable volume chamber from which a
`fluid can be expelled. though the outlet. the pluJlger comprising a plunger contact surface at a first
`end and a rod extending between the plunger contact surface and a rear portion. the plunger
`contact surface arranged tll contact lhe stopper. such that the plunger can be used to force the
`stopper towards the outlet end of1he body, reducing the volume of the variable volume chamber.
`
`characterised in that the fluid is an ophthalmic solution which comprises a V£GF-antagonist
`wherein:
`
`(a) the syringe has a nominal maximum fill volume ofbet~•een about 0.5ml and about 1ml,
`
`(b) the syringe is filled a do~ge volume of between !lbout 0.03ml and about 0.05ml of said
`VEGF antagonist ~olution.
`
`(c) the syringe barrel comprises less than about 500µg silicone oil, and
`
`(d) the VEGF antagonist solution. comprises no more than 2 particle;, ;::50µm io diameter per ml.
`'352 Application, Originally Filed Claim 1
`
`In a preliminaiy amendment on August 16, 2013, before any office actions had been
`
`received from the USPTO, claim 1 was amended by deleting most of the stiuctural limitations for
`
`the syringe as shown below (deleted material is sti·icken and newly added material is underlined).
`
`The preliminaiy amendment was signed by Andrew Holmes.
`
`16
`
`Novartis Exhibit 2006.0016
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Case 1:20-cv-00690-TJM-CFH Document 55 Filed 07/11/21 Page 17 of 52
`
`1.(currently amended)
`
`A pre-filled syringe for intravitreal injection, the syringe comprising
`
`a glass body forming a barrel, a stopper and a plunger, the body coffij;,fisiAg aA oullet at aA
`oo~aA{l-t~topper bOiRg arraAged WilAiR the bOEly 61:1011 tl1at a IFOAt 61:H1ase of~
`stof')f)Of and ll-le boely eleiine a ~•aiiable-vo!Ym~mGeHfGffi-Whisl=l a n1iid can be exi:>elled
`tl:lel:lii'I ll=lo 01:11101, tl=le i:>lungor eomprising a i,lunger cootaGt~rtace al a first end-ar-10--a-roo
`e11.ten1fo1g be~1.•een tl:ie plunger sor:ilact s11rfaco and a roar por1ion. tl:io pl1:1ngor cGntast syrface
`aFfBA!=JOel to eentaet lhe stepper, s1:10Ft that ll'le pl1:1nger Guf+-9e--ti500-to-feroe tAe stopi;er towarEls
`
`the Ol:ltlet end of the body, red1:1ciAg the ¥olumo of !Re variable vol1:1rne chamber. characlerisod
`in thal the fl1,1id is an and containing an ophthalmic solution which comprises a VEGF-antagonist.,
`wherein:
`
`(a) the syringe has a nominal maximum fill volume of between about 0.5ml and about 1ml,
`
`(b) the syringe is filled with a dosage volume of between about 0.03ml and about 0.05ml of said
`VEGF antagonist solution,
`
`(c} the syringe barrel comprises less than about 500µg silicone oil, and
`
`(d) the VEGF antagonist solution comprises no more than 2 particles ~50µm in diameter per ml.
`
`'352 Application, First Amendment to Claim 1
`
`The '352 Application was examined by USPTO examiner Aaiii Bhatia Berdichevsky (the
`
`"Syringe Examiner"). In a first office action on May 14, 2014, the Syringe Examiner issued a non(cid:173)
`
`final rejection determining that claim 1 was both anticipated and obvious in view of a published
`
`patent application identified as WO 2007/035621 to Scypinski. In addition, the Syringe Examiner
`
`determined that all of the other pending claims (2-32) were either anticipated by Scypinski, or
`
`obvious in view of Scypinski alone of in view of a second published patent application, US
`
`2011/0276005 to Hioki.
`
`On August 13, 2014, the Novaiiis applicant submitted a response to the non-final rejection.
`
`The response included an amendment to claim 1, as shown below, that amended the claimed range
`
`of silicone oil from "less than about 500 µg" to "from about 1 µg to 500 µ.