During the week of October 1, 2018, the Board issued seven Final Written Decisions and two institution decisions in Technology Center 1600.  The decisions are summarized as follows:

Final Written Decisions Related to Genentech Patents

Six of the seven Final Written Decisions are from inter partes review (“IPR”) proceedings against three of Genentech Inc.’s patents related to methods for treating cancers characterized by the overexpression of ErB2 receptor (i.e., HER2), which is associated with breast cancer.  Genentech’s U.S. Patent No. 6,627,196 (“the ’196 patent”) and U.S. Patent No. 7,371,379 (“the ’379 patent”) are from the same patent family and are directed to dosing regimens of anti-ErbB2 antibodies (e.g., trastuzumab, otherwise known as Herceptin®); whereas, U.S. Patent No. 7,892,549 (“the ’549 patent”) is from a different patent family and is directed to a combination therapy using three different agents including anti-ErbB2 antibodies.  Hospira, Inc. filed IPRs against the ’196, ’379, and ’549 patents, which were instituted by the Board.  Following those institution decisions, Samsung Bioepis Co., Ltd. filed substantially identical petitions and requested joinder with the Hospira proceedings, which the Board granted.  Celltrion filed separate IPRs against the ’196, ’379, and ’549 patents.  In both sets of IPRs, the Board upheld patentability of all challenged claims of the ’196 and ’379 patents but held the challenged claims of the ’549 patent unpatentable.

  • Hospira, Inc. and Samsung Bioepis Co., Ltd. v. Genentech, Inc., IPR2017-00737 (Final Written Decision October 3, 2018). Petitioners Hospira and Samsung challenged the patentability of claims 1-17 of the ’549 patent as being obvious over Baselga ’97, Baselga ’96, Baselga ’94, Gelmon, Drebin, and Presta.  IPR2017-00737 at 8-9.  The Board found all challenged claims obvious over said prior art references.  The Board further denied Patent Owner’s motion to replace the challenged claims with new claims 18-20 because the Board found the new claims lacked written description and would have been obvious.  at 51-52.

Issued claims 1-17

The ’549 patent issued with independent claims 1, 5, and 16, which are directed to a three-drug combination treatment of breast cancer that overexpresses the ErbB2 receptor.  The combination treatment includes: (1) an anti-ErbB2 antibody that binds to epitope 4D5 (e.g., humanized antibodies such as trastuzumab); (2) a taxoid (e.g., paclitaxel); and (3) a therapeutic agent in “an amount effective to extend the time to disease progression [TTP] in the human patient.”  Id. at 7-8.  The therapeutic agent recited in independent claims 1 and 16 is a further growth inhibitory agent effective to extend the time to disease progression.  Id.  Independent claim 16 further recites a negative limitation that the combination is administered in the absence of an anthracycline derivative.  Id.  Dependent claims of independent claim 5 recite other therapeutic agents, such as another ErbB2 antibody, and VEGF.  Id. 

The Board agreed with Petitioners that “an amount effective to extend the time to disease progression in the human patient” should concern a comparison to an untreated patient because Patent Owner adopted the comparison to an untreated patient to obtain allowance of the challenged claims.  Id. at 13.  The Board agreed with Petitioners that a person of ordinary skill in the art (“POSITA”) would have had a reasonable expectation that the three-drug combination at the disclosed doses for each drug would achieve the claimed efficacy.  Id. at 26.  In particular, the Board agreed with Petitioners that (1) prior art disclosed uses of anti-ErbB2 antibodies, paclitaxel, and cisplatin in human patients; (2) two-drug combinations of each of the three agents showed synergistic effects; (3) drug combinations were routinely used to fight breast cancer; and (4) combination therapy acting on different and complementary pathways (e.g., the claimed three-drug treatment) were known to have a greater probability to show synergistic effects without drug resistance or enhanced toxicity.  Id. at 23.  As Patent Owner did not suggest that a POSITA would believe that the addition of paclitaxel and/or a further growth inhibitory agent would negate the increased TTP mediated by rhuMAb HER2, the Board agreed with Petitioners and found the challenged claims obvious.  Moreover, Petitioners argued that due to the susceptibility to anthracycline cardiotoxicity and/or resistance, there was a need to use alternative treatments such as paclitaxel for patients treated with anthracycline before.  Id. at 30.  Thus, the Board found the limitation “in the absence of an anthracycline derivative” recited in the claims was also obvious.  Additionally, the Board found the challenged claims unpatentable even if the Board adopted Patent Owner’s construction that a patient treated with taxoid alone is the proper comparator.  The Board found the claimed efficacy benefit (extended TTP) would have been expected under Patent Owner’s construction.  Id. at 42.

New claims 18-20

Patent Owner filed a motion to replace all challenged claims with new claims 18-20 which recite a three-drug combination treatment of rhuMAb HER2 (i.e., trastuzumab), paclitaxel and a growth inhibitor agent “in an amount effective to extend the time to disease progression in the human patient, as compared to paclitaxel alone,” optionally in the absence of an anthracycline derivative.  Id. at 47-48.  The Board agreed with Petitioners that Patent Owner failed to show possession of the claimed three-drug combination treatment when Patent Owner relied on a clinical study of a two-drug combination of trastuzumab and paclitaxel to show the clinical efficacy of the claimed three-drug combination treatment.  Id. at 51-52.  Furthermore, as Patent Owner adopted essentially the same arguments for the patentability of the new claims and the challenged claims 1-17, the Board was not persuaded and found the new claims unpatentable.  Consequently, the Board denied Patent Owner’s motion to amend.  Id. at 52.

Other motions

Petitioners and Patent Owner filed motions to exclude certain evidence and to seal certain records.  The Board denied all motions to exclude evidence.  The Board granted several motions to seal confidential documents and denied several motions that the parties failed to support with good cause.  In particular, one of Patent Owner’s motions to exclude evidence related to the declaration of Petitioners’ preclinical expert because the expert was not “a clinical or medical oncologist,” and therefore not a POSITA.  Id. at 53.  The Board agreed with Petitioners that an expert witness may not need to be a POSITA.  Id. at 53-54.  Neither was Patent Owner’s own expert a “clinical or medical oncologist” and Patent Owner’s own expert also relied on Petitioners’ preclinical expert’s declaration.  The Board denied Patent Owner’s motions to exclude.

 

  • Celltrion, Inc. v. Genentech, Inc., IPR2017-01122 (Final Written Decision October 3, 2018). Petitioner Celltrion, Inc. challenged the patentability of claims 1-11 and 14-17 of the ’549 patent.  The Board agreed with Petitioner that all challenged claims were unpatentable for obviousness over the prior art.  IPR2017-01122 at 61.  The ’549 patent relates to the treatment of breast cancers that overexpress HER2/ErbB2 through administering “a therapeutically effective amount of a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline derivative, e.g. doxorubicin or epirubicin, in the absence of an anthracycline derivative to the human patient.”  Id. at 6.

Petitioner sought to invalidate the ’549 patent based on the combination of Baselga 1996, Seidman 1996, Pegram, 1995 TAXOL PDR and the knowledge of a POSITA.  Id. at 7-8.  Independent claims 1 and 16 require administering a combination of an anti-ErbB2 antibody, a taxoid, and a further agent “in an amount effective to extend the time to disease progression [TTP] in a human patient.”  Similar to the decision in IPR2017-00737, the Board construed the phrase “extend the time to disease progression” to concern a comparison of the combination of an anti-ErbB2 antibody and taxoid administered in an effective amount to no treatment because the Patent Owner relied on this construction during prosecution to get the claims allowed.  Id. at 11-12.

The Board accepted Petitioner’s argument that the challenged claims would have been obvious over the combination of Baselga 1996, Seidman 1996, Pegram and 1995 TAXOL PDR in view of the knowledge of a POSITA.  Id. at 22.  A POSITA would have been motivated to combine the substances based on the “dire need for treatments of HER-2 positive breast cancer” and the proven efficacy of the substances in treating this breast cancer.  Id.  A POSITA would have had a reasonable expectation that the three-drug combination addressed in the ’549 patent claims would have been safe and effective.  Id. at 25.

Other motions

In addition, similar to the decision in IPR2017-00737, the Board rejected Patent Owner’s Motion to Amend.  Patent Owner sought to amend the claims to make explicit that the claimed comparison for “extend time to disease progression” is between a patient treated with the drug combination provided by the ’549 patent and a patient treated with paclitaxel alone.  The Board agreed with Petitioner that the substitute claims added new subject matter because a POSITA would not have recognized from the priority documents relied upon by the Patent Owner that the Patent Owner had possession of the drug combination claimed.  Id. at 52-53.  “In determining whether claims introduce new matter, we look to whether the original application provides adequate written description support for the claims.”  Id. at 51.  The Board also rejected the Motion to Amend because the proposed amendments would not cure obviousness of the claimed invention in view of the art of record.

 

  • Hospira, Inc., and Samsung Bioepis Co., Ltd. v. Genentech, Inc., IPR2017-00804 (Final Written Decision October 3, 2018) and Hospira, Inc., and Samsung Bioepis Co., Ltd. v. Genentech, Inc., IPR2017-00805 (Final Written Decision October 3, 2018). Petitioners Hospira and Samsung challenged the patentability of claims 1-3, 5, 7, 9-11, and 17-33 of the ’196 patent and claims 1-3, 5, 7, 9-11, 16-28, and 30-40 of the ’379 patent as being obvious over the Herceptin label, Baselga ’96, and Pegram and the knowledge of a POSITA.  IPR2017-00804 at 7, IPR2017-00805 at 7.  The ’379 patent is a divisional application of the application that issued as the ’196 patent.  IPR2017-00805 at 3-4.[1]  The ’196 and ’379 patent claims are directed to dosing regimens for the treatment of cancer in which an anti-ErbB2 antibody (g., trastuzumab) is administered at an initial dose, followed by administration of the antibody at subsequent doses that are the same or less than the initial dose and separated in time by at least about two weeks.  Id. at 11-12.  For the obviousness analysis, both parties and the Board assumed a treatment method in which trastuzumab is administered once every three weeks.  Id. at 12.

Regarding motivation, the Board agreed with Petitioners that a POSITA would have been motivated to decrease the dosing interval of trastuzumab taught in the prior art from a weekly dose to a tri-weekly dose because it would be more cost-effective and convenient for patients and would enhance patient compliance.  Id. at 16-19.  The Board also agreed that a POSITA would be motivated to administer a tri-weekly dose of trastuzumab because it would match the dosing schedule of other therapies used in combination with trastuzumab.  Id. at 19-20.

Although the Board found motivation to select a tri-weekly dose of trastuzumab, the Board found that Petitioners did not meet their burden of establishing a reasonable expectation that the extended dosing interval would be successful.  Id. at 22-23. Petitioners argued that a POSITA would have extended the dosing interval of trastuzumab based on the linear pharmacokinetics analysis of trastuzumab set forth by Petitioners’ expert.  Id. at 22-23.  The Board disagreed and found that the prior art did not contain sufficient data to support Petitioners’ expert’s analysis or the feasibility or viability of a tri-weekly dosing regimen.  Id. at 22-23.  Instead, the Board found that the prior art highlighted the uncertainty of trastuzumab’s pharmacokinetics and found Petitioners’ expert’s analysis to be based on impermissible hindsight.  Id. at 26.  Accordingly, the Board determined that Petitioners had not shown by a preponderance of the evidence that the ’196 and ’379 patent claims at issue are unpatentable as obvious.  Id. at 33-34.

 

  • Celltrion, Inc. v. Genentech, Inc., IPR2017-01139 (Final Written Decision October 3, 2018) and Celltrion, Inc. v. Genentech, Inc., IPR2017-01140 (Final Written Decision October 3, 2018). Similar to the Petitioners in IPR2017-00804 and IPR2017-00805, Petitioner Celltrion challenged claims 1-3, 5, 7, 9-11, and 17-33 of the ’196 patent (with the addition of claims 13-15); and claims 1-3, 5, 7, 9-11, 13-28, and 30-40 of the ’379 patent.  IPR2017-01139 at 1, IPR2017-01140 at 1.  Celltrion argued obviousness of the ’196 and ’376 patent claims over Slamon, Watanabe, Baselga ’96, and Pegram.  IPR2017-01139 at 6.[2]

Like IPR2017-00804 and IPR2017-00805, the Board agreed that a POSITA would be motivated to extend the trastuzumab dosing interval from once weekly to tri-weekly to enhance patient convenience and compliance, and to match the dosing intervals of chemotherapies used in combination with trastuzumab.  Id. at 14-19.  However, the Board agreed with Patent Owner that Celltrion did not meet its burden to establish that the prior art provided motivation for a POSITA to modify the loading and maintenance doses required by the claims.  Id. at 20.  Specifically, Celltrion argued that a POSITA would have recognized the importance of dose intensity (i.e., the amount of drug administered over a period of time) when modifying a dosing schedule of trastuzumab.  Id. at 20-22.  But the Board agreed with Patent Owner that Celltrion lacked sufficient evidence to show that a POSITA would apply the concept of dose intensity, which is a dosing strategy for chemotherapy, to an antibody treatment.  Id. at 23-24.  Accordingly, similar to the decisions in IPR2017-00804 and IPR2017-00805, the Board determined that Petitioners had not shown by a preponderance of the evidence that the ’196 and ’379 patent claims at issue are unpatentable as obvious.  Id. at 24, 26.

Other Final Written Decision

  • Celltrion, Inc. v. Biogen Inc., IPR2017-01095 (Final Written Decision October 4, 2018). Petitioner Celltrion challenged claims of U.S. Patent No. 9,296,821 (“the ’821 patent”) on one ground of anticipation based on the Marcus reference and on four grounds of obviousness: (1) Marcus and U.S. Patent No. 5,736,137 (“the ’137 patent”); (2) Czuczman, IDEC 10-K/A, Foon, and Dana; (3) Czuczman, IDEC 10-K/A, Foon, Dana, Link, and Piro; and (4) Czuczman, IDEC 10-K/A, Foon, Dana, Link, Piro, and the ’137 Patent. IPR2017-01095 at 5.  The ’821 patent is directed to methods for treating B-cell lymphomas including low grade or follicular non-Hodgkin’s lymphoma (“NHL”), by administering chimeric anti-CD20 antibodies in combination with chemotherapy.  In particular, the independent claims at issue recite, inter alia, “[a] method of treating low grade or follicular non-Hodgkin’s lymphoma (NHL) comprising administering a therapeutically effective amount of rituximab during a chemotherapeutic regimen, wherein the chemotherapeutic regimen consists of cyclophosphamide, vincristine, and prednisone (CVP therapy), wherein the method provides a synergistic effect in the patient.”  The Board determined that Petitioner showed by a preponderance of the evidence that claims 1-6 of the ’821 patent are unpatentable.  at 3.

Regarding anticipation of claims 1-6 in view of Marcus, the Board found that Petitioner established that the priority application of the ’821 patent, filed August 11, 1999, lacks written description support for independent claim 4 and dependent claims 5 and 6.  The Board found claims 4-6 were instead only entitled to the June 15, 2012 filing date of the application that issued as the ’821 patent.  Id. at 28 and 29.  Accordingly, the Board found that Marcus, publicly available as of 2005, is not prior art to claims 1-3, which each depend from claim 1, but is prior art to claims 4-6.  Id.  Although Patent Owner asserted that Petitioner failed to establish that Marcus disclosed the claimed “beneficial synergistic effect,” Petitioner argued that Patent Owner’s own chart submitted during prosecution to support the construction of “beneficial synergistic effect” cited the disclosure in Marcus.  Id. at 31.  The Board “agree[d] with the Petitioner that Patent Owner’s argument and evidence support the Petitioner’s contention that Marcus discloses that limitation.”  Id. at 32.  The Board thus concluded that claims 4-6 are unpatentable as anticipated by Marcus.  Id. at 35, 71.

Regarding the first ground of obviousness, the Board concluded that claim 6 is unpatentable as obvious over Marcus and the ’137 patent because Petitioner relied on Marcus in the same manner as for anticipation, and Patent Owner did not raise any substantive arguments related to this ground.  Id. at 36.

In determining obviousness for the remaining grounds, the Board found that Petitioner had not established that IDEC 10-K/A was publicly available to be considered a printed publication, and therefore analyzed the grounds without considering IDEC 10-K/A.  Id. at 44 and 45.

Concerning the obviousness challenge to claims 1-3 over the combination of Czuczman, Foon, and Dana, the Board concluded that a POSITA would have understood that Czuczman taught the claimed rituximab limitation and that the chemotherapeutic regimen disclosed in Czuczman is CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone], which is similar to the claimed CVP therapy limitation.  Id. at 49-50.  The Board asserted that “a person of skill in the art would have understood from Foon and Dana that CHOP and CVP were two of three combination therapies that were known at the time of the invention to be useful for treating low grade NHL” and that “Petitioner’s proposed modification of Czuczman amounts to no more than a simple substitution of one known and useful chemotherapy for treating low grade NHL for another.”  Id. at 55.  The Board further found that a POSITA would have had a reasonable expectation of success in making the modification because “Czuczman describes rituximab as having ‘synergy with chemotherapeutic agents.”  Id. at 61.  The Board concluded that claims 1-3 are unpatentable over Czuczman, Foon, and Dana and found that Patent Owner’s arguments alleging unexpected results did not outweigh their determination.  Id. at 65-66.  The Board likewise found that Petitioner also established that claim 3 was unpatentable over the combination of Czuczman, Foon, Dana, Piro, Link, and the ’137 Patent.  Id. at 69.

Concerning the obviousness challenge to claims 4-6 over Czuczman, Foon, Dana, Piro and Link, Petitioner asserted that the teachings of the combination “would have provided a person of skill in the art with the motivation ‘to optimize the dosing regimens taught in Czuczman, Link and Piro to once every 3 weeks for 6 doses and to once every 3 weeks for 8 doses’ [as recited by claim 4] with a reasonable expectation of success.”  Id. at 67.  However, the Board found that none of the cited references “teaches or suggests treating low grade follicular NHL on a schedule of ‘once every 3 weeks…[c]onsequently, the basis for Petitioner’s optimization is inadequately supported.”  Id. at 68.  The Board concluded that Petitioner did not establish by a preponderance of the evidence that claims 4-6 are unpatentable over the asserted prior art combination.  The Board similarly found that Petitioner did not also establish by a preponderance of the evidence that claim 6 was unpatentable over the combination of Czuczman, Foon, Dana, Piro, Link, and the ’137 Patent.  Id. at 70.

Institution Decisions

  • Collegium Pharmaceutical Inc., v. Purdue Pharma L.P. et al., PGR2018-00048 (Decision Instituting Post-Grant Review October 4, 2018). Petitioner Collegium filed a petition requesting post-grant review of Purdue Pharma’s U.S. Patent No. 9,693,961 (‘the ’961 patent”). The ’961 patent claims are related to controlled release oral dosage forms comprising therapeutically effective amounts of drugs susceptible to abuse with excipients such as gelling agents, that impart a viscosity unsuitable for administration via parenteral or nasal routes when crushed and mixed with an aqueous liquid.

Petitioner first argued that the ’961 patent was eligible for post-grant review because the application to which the patent claimed priority did not provide written description support for the claims.  The Board agreed with Petitioner, stating that the provisional application failed to demonstrate disclosure of the concept that a certain binder material may be used in the formulation.

Petitioner then asserted that the claims of the ’961 patent were unpatentable for (1) lack of written description, (2) lack of enablement, (3) indefiniteness, and (4) anticipation.

With respect to written description, the Board instituted post-grant review for the same reasons it found the patent eligible for post-grant review.

With respect to enablement, the Board found that Petitioner had not demonstrated likely success based on commercially known formulations and methods of manufacturing sustained-released doses disclosed in the specification and known in the art.  Of note, however, the Board stated that it would revisit the ground based on the record that developed during the proceedings.

As to indefiniteness, while Patent Owner did not address this ground in its response, the Board noted it was not persuaded that Petitioner was likely to succeed in arguing the term “abuse deterrent dosage form” was indefinite.  The Board noted the claims defined the term as related to when the dosage form was subjected to heating and identified in the specification specific ingredients that could help achieve the function.  The Board again noted it would reconsider its opinion based on a more fully developed record.

Finally, with respect to anticipation, the Board noted that Petitioner had provided a claim chart teaching how the challenged claims were anticipated by an identified prior art reference.  Without additional comment, the Board stated Petitioners were likely to succeed on their anticipation ground.

 

The Board found that the Examiner was aware of each of the references asserted by Indivior except for McAleer, which the Board concluded was cumulative in view of the prior art that the Examiner relied on during prosecution.  Id. at 9.  Indivior also argued that the Cremer reference, provided in an information disclosure statement (IDS), was not considered by the Examiner because it was only submitted in German, not English.  Id. at 11.  The Board, however, was not persuaded as it found it was reasonable to infer that during prosecution the Examiner considered the Canadian counterpart of Cremer, which is in English and substantially similar to Cremer.  Id. at 10.  Indivior also provided an expert opinion alleging that the references could be applied in a different light, but the Board did not find this persuasive in view of its findings regarding Cremer.  Id. at 11.

As such, the Board exercised its discretion to deny institution of IPR under 35 U.S.C. § 325(d) because Indivior presented substantially the same prior art previously presented to the Patent Office and failed to provide sufficient evidence to convince the Board to apply the references in a different light.  Id. at 12.

[1]           Citations are to IPR2017-00805 because the Final Written Decisions for IPR2017-00804 and IPR2017-00805 are substantially the same.

[2]           Citations are to IPR2017-01139 because the Final Written Decisions for IPR2017-01139 and IPR2017-01140 are substantially the same.