IN THE UNITED STATES DISTRICT COURT
`DISTRICT OF NEW JERSEY
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`Confidential
`Attorney’s Eyes Only
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`Case No. 3:17-cv-13151-PGS-TJB
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`____________________________________
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`BRACCO DIAGNOSTICS INC.,
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`Plaintiff,
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`v.
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`MAIA PHARMACEUTICALS, INC.,
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`Defendant.
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`MAIA PHARMACEUTICALS, INC.
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`Counterclaimant,
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`v.
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`BRACCO DIAGNOSTICS INC.,
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`Counterclaim Defendant.
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`PLAINTIFF’S RESPONSES TO INVALIDITY CONTENTIONS
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`Bracco’s Responses to Maia’s Invalidity Contentions
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`I.
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`Plaintiff Bracco Diagnostics Inc. (“Bracco”) provides Bracco’s Responses to Invalidity
`Contentions pursuant to the Local Patent Rules, including L.Pat.R. 3.6(h), which states:
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`Not more than 45 days after the disclosure of “Invalidity Contentions” as required
`by L. Pat. R. 3.6(c), the party defending the validity of the patent shall serve on
`each other party its “Responses to Invalidity Contentions” as required under L.
`Pat. R. 3.4A.
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`L.Pat.R. 3.4A, referred to in the rule recited above, states:1
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`[Not later than 14 days after service upon it of the “Invalidity Contentions,”] each
`party defending the validity of the patent shall serve on all parties its “Responses
`to Invalidity Contentions” which shall include the following:
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`[(a) For each item of asserted prior art, the identification of each limitation of
`each
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`1 Bracco notes that the preamble to L.Pat.R. 3.4A states 14 days (in brackets above) but that is
`not applicable because of L.Pat.R. 3.6(h). Bracco also notes that Maia has not asserted that any
`claim of the ‘046 patent is invalid for anticipation in Maia’s Invalidity Contentions so 3.4A(a)
`(also in brackets above) does not apply to Bracco.
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`1
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`Bracco Ex. 2004
`Maia v. Bracco
`IPR2019-00345
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`asserted claim that the party believes is absent from the prior art, except for
`design patents, where the party shall supply an explanation why the prior art does
`not anticipate the claim;]
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`(b) If obviousness is alleged, an explanation of why the prior art does not render
`the asserted claim obvious;
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`(c) The party's responses shall follow the order of the invalidity chart required
`under L. Pat. R. 3.3(c), and shall set forth the party's agreement or disagreement
`with each allegation therein and the written basis thereof; and
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`(d) For each asserted grounds of invalidity under L.Pat.R. 3.3(d), a detailed
`explanation of how the asserted claim complies with 35 U.S.C. §112; and
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`(e) The production or the making available for inspection and copying of any
`document or thing that the party intends to rely on in support of its Responses
`herein.
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`Accompanying this disclosure is also Bracco’s production of documents required under L.Pat.R.
`3.4A(e), recited immediately above. This includes documents that were already produced,
`including Bracco’s Infringement Contentions that were provided to Maia separately. They show
`that Maia
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`In addition, Bracco refers to and will rely on Maia’s production of documents and certain
`positions that it has taken that support validity, namely:
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`Maia’s 505(b)(2) NDA in its entirety along with Bracco’s Infringement Contentions. The
`Maia 505(b)(2) NDA, as explained in detail in Bracco’s Infringement Contentions, demonstrates
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`Maia’s May 2, 2018 letter to the Court. In that letter Maia stated that it “is not contending that
`a single prior art reference teaches every element of the asserted claims.” In addition, Maia stated
`that “Maia has agreed to strike the portion of its Invalidity Contentions, on page 4, that
`incorporates by reference any prior art (including prosecution histories) that has not been
`produced by Maia in this case.” This includes the references cited on the face of the ‘046 patent
`and prosecution histories mentioned on page 4 of Maia’s Invalidity Contentions. Maia made
`many other representations in its letter but these representations were not correct. For example,
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`the letter alleges that Maia is asserting 55 references. However, only 40 references are
`specifically addressed in Maia’s Invalidity Contentions.
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`II. Maia’s Invalidity Contentions
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`Maia asserted purported defenses of obviousness, lack of enablement and lack of written
`description in its Invalidity Contentions. Maia made no other arguments based on any other
`grounds (e.g., Maia made no anticipation arguments). Thus, Maia’s Invalidity Contentions serve
`as an admission that the claimed subject matter of the ‘046 is novel and not anticipated by any
`prior art or prior work of anyone pursuant to 35 U.S.C. § 102.
`
`Maia also failed to assert a competent ground of obviousness pursuant to 35 U.S.C. § 103 against
`a single claim of the ‘046 patent. Pursuant to the Court’s March 27, 2018 Letter Order, Maia was
`required “to provide Plaintiff with the written basis for its Invalidity Contentions along with any
`disclosures under L.Pat.R. 3.4 (L.Pat.R. 3.6(c)-(d))” by April 26, 2018. Maia’s submission did
`not comply with the rules in several respects, including by failing to identify any particular prior
`art combinations it was asserting regarding its obviousness challenge to the claims of ‘046 patent.
`Maia also did not provide translations to two references it cited and failed to provide or
`otherwise define a “Kinevac Label” referred to in its contentions. Instead Maia provided groups
`of references without ever identifying any particular combinations of them it was asserting.
`Without providing any specific combinations, Maia then also failed to provide the Graham factor
`analysis for any combination, including failing to provide any motivation to combine the
`references and any likelihood of success. Maia’s obviousness challenge thus fails for these
`reasons alone. Maia also failed to show how any “separate” reference it was asserting could
`alone render any ‘046 patent claim obvious. Maia also did not provide translations to references
`it cited and failed to provide or otherwise define a “Kinevac Label” and other documents referred
`to in its contentions. In light of the foregoing, Bracco contends that nothing more is required of it
`to overcome Maia’s obviousness challenge. Any further response by Bracco should not be
`construed as implying that Maia made a prima facie case of obviousness anywhere in Maia’s
`Invalidity Contentions. By making the showing set forth below, Bracco is not waiving its right to
`move to strike and otherwise render inadmissible any further and/or withheld arguments by Maia
`concerning obviousness.
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`Bracco raised the issue about the failure to provide any specific single reference or combinations
`of references in its April 30, 2018 and May 7, 2018 letters to the Court and the Court clarified for
`Maia at the May 1, 2018 telephonic hearing that amendment of Maia’s Invalidity Contentions
`must comply with L.Pat.R. 3.7, which requires an order of the Court upon a timely application
`and showing of good cause, and the Federal Rules. The Court made it clear that under the
`scenario presented by Bracco, that if it were correct, Maia would not be permitted to amend its
`contentions in the future. The parties then met and conferred on the issue and Maia, lacking
`knowledge of what its contentions said, declined to amend its contentions. In sum, Bracco
`attempted to meet and confer on the issue on April 27, 2018 (Maia ignored this effort), Maia was
`clearly warned of the consequences of incomplete contentions and was given ample opportunity
`to amend its Invalidity Contentions due on April 26, 2018, but Maia declined to do so and should
`not be permitted to do so in the future. E.g., Warner Chilcott Co., LLC v. Milan Inc., 2015 WL
`3630970, Civil Action No. 13-6560 (MLC) (D.N.J. June 9, 2015) (states “Not For Publication”).
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`Maia’s assertion that the ‘046 patent claims lack an adequate written description and enablement
`also fail for lack of support and the failure to present a colorable argument as required by the
`Local Patent Rules and as a matter of law, as described below.
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`III. Maia’s Prior Art Does Not Render The ‘046 Patent Claims Obvious
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`Maia raises only obviousness as a defense in relation to the prior art. This operates as an
`admission from Maia that the claimed subject matter of the ‘046 patent is novel over the prior art.
`An invention that would have been obvious to a person of ordinary skill at the time of the
`invention is invalid. KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007); Graham v.
`John Deere Co., 383 U.S. 1 (1966). Maia’s invalidity arguments are fatally flawed for at least
`thirteen overarching reasons that render Maia’s arguments legally insufficient and without a
`colorable factual basis, as described below.
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`1. The Local Patent Rules required Maia to provide, with its obviousness challenge, “an
`explanation of why the prior art renders the asserted claim obvious, including an identification of
`any combinations of prior art showing obviousness.” L.Pat.R. 3.3(b). Maia never applied the
`Graham factors to assert a colorable claim of obviousness. KSR; Graham. Maia never provided a
`description of the level of ordinary skill in the art, which is a required showing in an obviousness
`challenge as a matter of law.
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`2. Maia also did not comply with the Local Patent Rules because it never provided a single
`“identification of a combination of prior art showing obviousness.” L.Pat.R. 3.3(b). Instead,
`Maia just presents very large groups of references without combining particular references
`together to attempt to make a prima facia case of obviousness. Specifically, Maia produced a list
`of forty prior art references and stated that they “separately or in any reasonable combination,
`render obvious one or more of the claims of the patent-in-suit under 35 U.S.C. § 103” (page 4 of
`Maia’s Contentions). Maia’s assertion has no specificity and provides no notice of a colorable
`defense. Bracco pointed this out, giving Maia an opportunity to amend its contentions, and the
`Court warned Maia that amendments could not be made in the future if Maia had not complied
`with the rules, but Maia never made a single amendment and never made a single combination,
`which is evidence that a combination of references to render the claims obvious cannot be made.
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`3. Without a single combination of prior art references made, Maia also failed to show why a
`person of ordinary skill in the art would be motivated to combine specific references. Motivation
`proof is required in a prima facia obviousness challenge as a matter of law. KSR; Graham.
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`4. Maia cites a very large number of references (i.e., 40) and requires virtually all of them to be
`somehow used to render the ‘046 patent claims allegedly obviousness. The use of such a large
`number of references needed to make an argument is evidence that the subject matter of the ‘046
`patent claims is non-obvious, as a person of ordinary skill in the art would not be led to pick and
`choose from so many references in the manner used by Maia, which uses impermissible
`hindsight and knowledge of the ‘046 patent to choose some embodiments from the prior art but
`not others without justification.
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`5. Maia never addressed how its invalidity arguments overcome the presumption of validity
`afforded the ‘046 patent claims.
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`6. In particular, Maia never compared the references it was citing to what the USPTO Examiner
`considered during the prosecution of the ‘046 patent to show that they were not cumulative to
`what had already been reviewed and overcome. For example, Maia’s closest prior art and most
`oft cited reference is the Nema and Wang references. These references were cited to the USPTO
`Examiner and overcome as not invalidating by themselves, together and in light of the other
`references of record in the prosecution of the ‘046 patent.
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`7. Maia never even attempted to overcome the Nema reference teaching that the art area
`applicable to the ‘046 patent was unpredictable and the results literally “unforeseen.” Nema
`states “there is no guarantee that the new drug product will be safe as excipients are combined
`with other additives and/or with a new drug, creating unforeseen potentiation or synergistic toxic
`effects.” (p. 166, emphasis added). See also, Bayol (col. 2, lines 54-64), Waterman (p. 19, 20,
`27), Arakawa (p. 308, 323), Wang 1999 (p. 175, 178), Li 1995 (p. 498), Audhya (pp. 5-7), Wang
`(p. S8, S22), Wang 2000 (pp. 50-51).
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`8. Maia never addressed the fact that each of its non-sincalide, non-patent references were
`reported in journals of novel and non-obvious scientific work directed to other drugs, peptides
`and proteins besides sincalide, demonstrating that the art is not predictable and it is “news” when
`stabilization attempts work on a new drug, peptide or protein. Likewise, the patent references
`Maia cited were non-obviousness inventions for their claims directed to what they had done and
`the inventors were attempting to obtain patents for a wide variety of different drugs, peptides
`and proteins, with particular sets of excipients, again demonstrating that the art is not predictable
`and the ‘046 patent claims are valid.
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`9. Maia never addressed that before the ‘046 patent, for more than 30 years, no one attempted to
`make a more stabilized, physiologically acceptable sincalide formulation, or any new sincalide
`formulations at all. If it were obvious as Maia asserts, then someone else would have done it
`before Bracco.
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`12. Maia never addressed the fact that its Kinevac® references directed to an early formulation
`from the 1970’s teach away from any combination of references, a motivation to combine them,
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`or even a general need to make a stabilized formulation as claimed in the ‘046 patent, as
`confirmed by the fact that no one until the inventors of the ‘046 patent did so.
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`13. Maia never addressed the fact that its remaining, non-Kinevac®, references are all missing
`components of the ‘046 patent claims yet they are reporting on allegedly adequate solutions to
`the different problems they were addressing, providing further evidence that they teach away
`from any combination of references, a motivation to combine them, or even a general need to
`make a stabilized formulation as claimed in the ‘046 patent, as again confirmed by the fact that
`no one until the inventors of the ‘046 patent did so (e.g., MAIA0000079-85, 110-111, 118, 3046-
`81).
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`A.
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`The Scope And Content Of The Prior Art
`Significantly Differs From The “046 Patent Claims
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`Each of the 40 prior art references Maia cites was either before the Examiner, considered and
`overcome during the prosecution of the ‘046 patent, or it is less than cumulative to references that
`were before the Examiner, considered and overcome. See B0017245-18314 (which contains
`copies of prior art cited in the prosecution history of the ‘046 patent). Maia presents no new
`arguments in its obviousness challenges and hence cannot overcome the presumption of validity
`afforded the ‘046 patent. 35 U.S.C. § 282. Thus, although this fact is never mentioned by Maia,
`the Ondetti ‘406 (i.e., Ondetti et al., U.S. Patent No. 3,723,406) and the Nema and Wang
`references, were all already considered by the Examiner and overcome. This renders the related
`Maia references less than cumulative (i.e., USP 24, Kinevac® Label, Sato, Bayol, Sandow,
`Audhya, Hanyu, Bacarese-Hamilton, Keyt, Yamazaki, Pietras, Swift, Li, Waterman, Arakawa, Li
`1995, Wang 1999, Zhou, Wang 1980, Akers, Handbook, Dix, Foster, Matten, Wang 2000, Voet,
`Hellerband, De Felippis, Aisui and Minoru, are less than cumulative, less relevant (i.e., they add
`nothing to the prior art that was considered) than Ondetti ‘406, Nema and Wang)).
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`Specifically, in its contentions, Maia asserts that Nema and Wang disclose all of the elements of
`the ‘046 patent except for sincalide (pp. 7-9). Maia has already admitted several times that no
`single reference has all of the elements of the claims (e.g., see above). Therefore, Mai’s
`contention is an acknowledgement that all of the other non-clinical references (i.e., USP 24,
`Kinevac® Label, Sato, Bayol, Sandow, Audhya, Hanyu, Bacarese-Hamilton, Keyt, Yamazaki,
`Pietras, Swift, Li, Waterman, Arakawa, Li 1995, Wang 1999, Zhou, Wang 1980, Akers,
`Handbook, Dix, Foster, Matten, Wang 2000, Voet, Hellerband, De Felippis, Aisui and Minoru)
`are cumulative to Ondetti ‘406, Nema and Wang, which are three references among others that
`the USPTO and the Examiner already considered in the prosecution history of the ‘046 patent.
`Ondetti ‘406, Nema and Wang were overcome and the ‘046 patent was permitted to issue over
`them, affording the ‘046 patent a presumption of validity. 35 U.S.C. § 282. Therefore, under
`Maia’s own analysis there is nothing new here and the ‘046 patent is valid.
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`The same is true concerning the clinical evidence that was considered by the Examiner and
`overcome (viz., ‘046 patent, the references listed on pages 1 and 2; B0017245-18314). This prior
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`art also renders the clinical-related references Maia cites less than cumulative and less relevant
`(i.e., they add nothing to the prior art that was considered) than what the Examiner considered
`(e.g., Doty, Meyers, Sawaf, Krishnamurthy, Chen, Amarai, Vyas).
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`None of the references, alone or in combination, renders the ‘046 patent claims obvious. At least
`nine of Maia’s references state unequivocally that the art is unpredictable and each drug, like
`sincalide, cannot be stabilized by any rote method from the prior art, but instead it must be taken
`up on a case-by-case basis after extensive study and experimentation on a trial-by-error basis.
`(e.g., Bayol (col. 2, lines 54-64), Waterman (p. 19, 27), Arakawa (p. 308, 323), Wang 1999 (p.
`175, 178), Nema (p. 166), Li 1995 (p. 498), Audhya (pp. 5-7), Wang (p. S8, S22), Wang 2000
`(pp. 50-51)). Perhaps the summary of the art closest in time to the ‘046 patent filing is Maia’s
`Wang 2000 reference. It summarizes the state of the art as follows:
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`“In summary, development of a lyophilized protein product usually takes an
`enormous amount of time, labor, and effort, simply because there is no single,
`short, and mature pathway to follow in formulating such a product, and many
`experiments are done on a trial-and-error basis. This trend will continue until a
`breakthrough is achieved in understanding the basic behavior of proteins and their
`stabilization.” (p. 50-51).
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`The ‘046 patent marks that breakthrough for sincalide that Maia copied.
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`Bracco identifies and addresses the prior art asserted by Maia in the order presented on pages 5-
`25 of Maia’s Invalidity Contentions. Appendix A served herewith, which is incorporated by
`reference herein, addresses these same references and Maia’s arguments concerning them in the
`context of Maia’s claim chart served on April 26, 2018.
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`1. Ondetti: U.S. Patent No. 3,937,819 to Ondetti et al., entitled “Method of Stabilizing an
`Injectable Composition of a Cholecystokinin Active Octapeptide”
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`Ondetti (MAIA0004496-4498) states on its face that it issued on February 10, 1976, almost 30
`years before the ‘046 patent was filed. It was acquired by Bracco with the old formulation of
`Kinevac® and additional Ondetti patents (e.g., U.S. Patent No. 3,723,406) when Bracco bought
`the diagnostics division, including the products and research and development business, of
`Bristol Myers Squibb in 1994.
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`The subject matter of Ondetti was already disclosed in the “Background of the Invention” section
`of the ‘046 patent (col. 1, lines 8-40). It relates to the older form of Kinevac® that contained just
`sincalide and NaCl and is not covered by the claims of the ‘046 patent. Ondetti is therefore less
`relevant and less than cumulative to the references the Examiner considered in finding the claims
`of the ‘046 patent valid and non-obvious. The Ondetti patent discloses only an octapeptide,
`sincalide, and no other element of any of the independent claims of the ‘046 patent.
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`Ondetti states that “It is an object of the present invention to provide compositions of [a sulfated
`octapeptide] which are stable and retain the efficacy of the octapeptide during storage. Another
`object is to provide methods for preparing the stabilized compositions of the present invention”
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`(col. 1, lines 24-34). It also states that “The lyophilized material has excellent stability on storage
`and is readily reconstituted for injection …” (col. 2, lines 18-20). Claim 1 states that it is directed
`to “A method of enhancing the stability of the octapeptide … against degradation during storage,
`which comprises lyophilizing ….”
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`Because Ondetti teaches such a simplistic formulation and stabilization as adequate, it does not
`motivate a person of ordinary skill in the art to modify, seek out or otherwise combine its
`teaching with other knowledge or references. Nor does it suggest any likelihood of success from
`any such combination with other modifications, knowledge or references. In this regard it thus
`teaches away from all of the other elements of the claims of the ‘046 patent, which improve
`sincalide formulations.
`
`Maia’s Infringement Contentions states at p. 5 that the NaCl used in Ondetti is a
`“stabilizer/tonicity agent” without any support in the reference. Maia states the support is in the
`Abstract of Ondetti (i.e., “Id at Abstract”), but this is incorrect.
`
`Furthermore, the disclosure and single claim of Ondetti states that it enhances stability by
`lyophilizing a solution containing an octapeptide and sodium chloride and therefore it does not
`teach, suggest or motivate a person of skill in the art about anything relevant concerning the
`claims of the ‘046 patent, alone or in combination with any other reference cited by Maia.
`
`In addition, Ondetti issued on February 10, 1976. Until the ‘046 patent subject matter was
`invented and claimed by Bracco, no one in the entire pharmaceutical field attempted to use the
`Ondetti teachings to improve Kenevac® or sincalide formulations, alone or in combination with
`other knowledge or references, which is additional evidence of non-obviousness of the claims of
`the ‘046 patent demonstrating a failure of others and long felt need.
`
`In this regard, Ondetti describes the older formulation of Kenevac® that is not covered by the
`‘046 patent claims as suffering from potency variability and the need for a 20% overage of
`sincalide (e.g., col. 1, line 8 to col., 2, line 57). There was a failure of others and long felt need
`for the claimed subject matter of the ‘046 patent that persons of ordinary skill in the art did not
`and could not use Ondetti alone, or in combination with other knowledge or references, to meet.
`Bracco’s extensive work, as reflected in the substantial teaching and examples of the ‘046 patent,
`which underlies the claimed subject matter of the ‘046 patent, is further evidence of the
`inventiveness of the claimed subject matter of the ‘046 patent. No one has successfully attempted
`to design around the claims of the ‘046 patent to date, more than 13 years from when the ‘046
`patent published. Also, the FDA permitted the total replacement of the older formulations for the
`new formulation of Kenevac® that is covered by the claims of the ‘046 patent.
`
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`Moreover, Maia in its research program described in the Maia 505(b)(2) NDA did not rely on
`Ondetti or anything like it in arriving at Maia’s Proposed Product. In fact, the Maia 505(b)(2)
`NDA describes Maia as failing to develop an ANDA product, or to design around the ‘046 patent,
`and then resorting to examining (i.e., experimentally and through a FOIA request to the FDA)
`the new formulation of Kinevac® that is described and claimed in the ‘046 patent in order to
`copy it. Maia also cited information from the ‘046 patent in its 505(b)(2) NDA as definitive. In
`fact, Bracco’s Infringement Contentions specifically show that Maia was unable to design
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`around Bracco’s patent, Maia studied and copied Bracco’s ‘046 patent and Kinevac® product
`that is covered by the ‘046 patent, and Maia relied on the ‘046 patent teachings to make Maia’s
`Proposed Product (e.g., MAIA0000019-22, 72, 79-85, 110-111, 118, 123-136, 198-215, 441,
`444-45, 448-575, 3046-81, 3297-3307, 3619-22).
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`If Maia or anyone else had followed the Ondetti teachings and made a sincalide product, it would
`not fall into the subject matter of the ‘046 patent claims. Thus, Maia impermissibly uses
`hindsight to pick and choose from references like Ondetti and not actually follow the Ondetti
`teaching. The USPTO Examiner was correct in allowing the ‘046 patent to issue over this
`reference alone or in combination with references like Nema that were cited in prosecution
`history.
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`2. Kinevac® Insert or Label: Bracco Diagnostics, Kinevac® Sincalide for Injection (1994)
`
`The document produced by Maia and identified as the “Kinevac Insert” or, sometimes (e.g.,
`claim 1(a)) “Kinevac Label” (MAIA0004876-78) is of unknown origin. Bracco objects to the
`authenticity and admissibility of the document, which have not been established by Maia. In
`claim 20 of its claim chart, Maia refers to a document as the Kinevac Label, which cannot be the
`same as MAIA0004876-78, because it is not prior art and it may relate to the current formulation
`of the drug. Thus, there is confusion on Maia’s part as to what it meant by the Kinevac Insert and
`the Kinevac Label.
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`The subject matter of the Kinevac® Label was already disclosed in the “Background of the
`Invention” section of the ‘046 patent (col. 1, lines 8-40). It relates to the older form of Kinevac®
`that contained just sincalide and NaCl and is not covered by the claims of the ‘046 patent. The
`Kinevac® Label is therefore less relevant and less than cumulative to the references the
`Examiner considered in finding the claims of the ‘046 patent valid and non-obvious. The
`Kinevac® Insert discloses only sincalide, and no other element of any of the independent claims
`of the ‘046 patent.
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`Because the Kinevac® Label teaches such a simplistic formulation and stabilization as adequate
`(e.g., “may be kept at room temperature and should be used within 24 hours of reconstitution”;
`prior to reconstitution vials can be stored “at room temperature”), it does not motivate a person
`of ordinary skill in the art to modify, seek out or otherwise combine its teaching with other
`knowledge or references. Nor does it suggest any likelihood of success from any such
`combination with other modifications, knowledge or references. In this regard it thus teaches
`away from all of the other elements of the claims of the ‘046 patent, which improve sincalide
`formulations.
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`Furthermore, the disclosure of the Kinevac® Label states that it is “a sterile nonpyrogenic
`lyophilized white powder… the air in the vial is replaced with nitrogen.” Thus, the Kinevac
`Label discloses that it is stable itself, using lyophilization and nitrogen to enhance its stability,
`and therefore it does not teach, suggest or motivate a person of skill in the art about anything
`relevant concerning the claims of the ‘046 patent, alone or in combination with any other
`reference cited by Maia.
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`In addition, the Kinevac® Label is dated 1994. Until the ‘046 patent subject matter was invented
`and claimed by Bracco, no one in the entire pharmaceutical field attempted to use the Kinevac®
`Label teachings to improve Kinevac® or sincalide formulations, alone or in combination with
`other knowledge or references, which is additional evidence of non-obviousness of the claims of
`the ‘046 patent demonstrating a failure of others and long felt need.
`
`In this regard, the Kinevac® Label describes the older formulation of Kinevac® that is not
`covered by the ‘046 patent claims as suffering from potency variability and the need for a 20%
`overage of sincalide (e.g., col. 1, line 8 to col., 2, line 57). There was a failure of others and long
`felt need for the claimed subject matter of the ‘046 patent that persons of ordinary skill in the art
`did not and could not use the Kinevac® Label alone, or in combination with other knowledge or
`references, to meet. Bracco’s extensive work, as reflected in the substantial teaching and
`examples of the ‘046 patent, which underlies the claimed subject matter of the ‘046 patent, is
`further evidence of the inventiveness of the claimed subject matter of the ‘046 patent. No one has
`successfully attempted to design around the claims of the ‘046 patent to date, many years before
`when the ‘046 patent published. Also, the FDA permitted the total replacement of the older
`formulations for the new formulation of Kinevac® that is covered by the claims of the ‘046
`patent.
`
`
`Moreover, Maia in its research program described in the Maia 505(b)(2) NDA did not rely on the
`Kinevac® Label or anything like it in arriving at Maia’s Proposed Product. In fact, the Maia
`505(b)(2) NDA describes Maia as failing to develop an ANDA product, or to design around the
`‘046 patent, and then resorting to examining (i.e., experimentally and through a FOIA request to
`the FDA) the new formulation of Kinevac® that is described and claimed in the ‘046 patent in
`order to copy it. Maia also cited information from the ‘046 patent in its 505(b)(2) NDA as
`definitive. In fact, Bracco’s Infringement Contentions specifically show that Maia was unable to
`design around Bracco’s patent, Maia studied and copied Bracco’s ‘046 patent and Kinevac®
`product that is covered by the ‘046 patent, and Maia relied on the ‘046 patent teachings to make
`Maia’s Proposed Product (e.g., MAIA0000019-22, 72, 79-85, 110-111, 118, 123-136, 198-215,
`441, 444-45, 448-575, 3046-81, 3297-3307, 3619-22).
`
`If Maia or anyone else had followed this reference’s teachings and made a sincalide product, it
`would not fall into the subject matter of the ‘046 patent claims. Thus, Maia impermissibly uses
`hindsight to pick and choose from references like this one and not actually follow the references’
`teaching.
`
`3. USP 24: U.S. Pharmacopeia & National Formulary 24, The National Formulary 19,
`“Sincalide for Injection” 1522-1523 (2000)
`
`The document produced by Maia (MAIA0004746-4750) labeled “USP 24” contains an entry for
`“Sincalide for Injection,” including a guinea pig gall bladder assay.
`
`The subject matter of USP 24 was already disclosed in the “Background of the Invention”
`section of the ‘046 patent (col. 1, lines 8-40). It relates to the older form of Kinevac® that
`contained just sincalide and NaCl and is not covered by the claims of the ‘046 patent. USP 24 is
`therefore less relevant and less than cumulative to the references the Examiner considered in
`
`10
`
`
`
`

`

`finding the claims of the ‘046 patent valid and non-obvious. USP 24 discloses only an
`octapeptide, sincalide, and no other element of any of the independent claims of the ‘046 patent.
`
`Because USP 24 teaches such a simplistic formulation with its stabilization at that time as
`adequate, it does not motivate a person of ordinary skill in the art to modify, seek out or
`otherwise combine its teaching with other knowledge or references. Nor does it suggest any
`likelihood of success from any such combination with other modifications, knowledge or
`references. In this regard it thus teaches away from all of the other elements of the claims of the
`‘046 patent, which improve sincalide formulations.
`
`Furthermore, the disclosure of the USP 24 states that Sincalide for Injection enhances stability by
`lyophilizing a solution containing an octapeptide of cholecystokinin and sodium chloride and
`therefore it does not teach, suggest or motivate a person of skill in the art about anything relevant
`concerning the claims of the ‘046 patent, alone or in combination with any other reference cited
`by Maia.
`
`In addition, USP 24 is dated November 2000. Until the ‘046 patent subject matter was invented
`and claimed by Bracco, no one in the entire pharmaceutical field attempted to use the USP 24
`teachings to improve Kenevac® or sincalide formulations, alone or in combination with other
`knowledge or references, which is additional evidence of non-obviousness of the claims of the
`‘046 patent demonstrating a failure of others and long felt need.
`
`In this regard, USP 24 describes the older formulation