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PTAB: Shire Can Amend Multiple Dependent claim to Depend on Fewer Claims

In IPR2015-02009, Shire moved to amend claims of U.S. Reissued Patent RE 42,096 by cancelling all of the claims instituted for trial and proposing one substitute claim.  Specifically, Shire proposed that new claim 26 be substituted for claim 25 so that there would be no claim remaining subject to inter partes review.

25. The pharmaceutical composition of any one of claims 2, 13

or 18 to 20 wherein the pharmaceutically active amphetamine

salt in (a) and (b) comprises mixed amphetamine salts.

26. The pharmaceutical composition of any one of claims 2[[,]]

or 13 or 18 to 20 wherein the pharmaceutically active

amphetamine salt in (a) and (b) comprises mixed amphetamine

salts.

The PTAB allowed Shire’s amendment since “multiple dependent substitute claim 26 merely has the effect of eliminating three claims dependent on instituted claims 18–20, and preserving two claims dependent from non-instituted claims 2 and 13.. . effectively, no claim is being amended, and claims are only being cancelled, because claims 18–24 are being removed, and proposed claim 26 removes three multiple dependent claims (claim 25 as it depends from claims 18–20) and no other changes to the claims are being made.”

The PTAB’s decision in this case only applies to a situation where a patentee is canceling claims and not making other changes.

Federal Circuit: PTAB Can Reach a Different Conclusion than a District Court

On April 4, 2017, the Federal Circuit held that the PTAB can find the claims of a patent obvious even if a district court has previously found the claims to be non-obvious. The Federal Circuit based its holding on the difference in prior art that was considered in each proceeding and the lower burden of proof in an IPR proceeding to invalidate a patent.  Below is an excerpt from the Federal Circuit's opinion.

Novartis AG v. Noven Pharmaceuticals Inc. (Fed. Cir. 2017)

http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/16-1678.Opinion.4-3-2017.1.PDF

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Novartis alleges that a fundamental legal error pervades the PTAB’s Final Written Decisions: the PTAB unlawfully reached different conclusions than our court and the U.S. District Court for the District of Delaware (“Delaware District Court”), which addressed the “same” arguments and the “same” evidence and found the Asserted Claims nonobvious in two prior opinions. Appellants’ Br. 29; see id. at 35–39, 46–47, 52–56, 60–62 (discussing Novartis Pharm. Corp. v. Watson Labs., Inc., 611 F. App’x 988 (Fed. Cir. 2015) and Novartis Pharm. Corp. v. Noven Pharm., Inc. (Noven D. Del.), 125 F. Supp. 3d 474 (D. Del. 2015)). In support of that position, Novartis relies substantially on a single sentence from our decision in In re Baxter International, Inc. See, e.g., id. at 30 (discussing 678 F.3d 1357, 1365 (Fed. Cir. 2012)).

Novartis’s argument fails on factual and legal grounds. As an initial matter, the record here differed from that in the prior litigation, meaning that Novartis’s argument rests on a faulty factual predicate. With respect to Watson, the PTAB found that it “does not control here because [Appellee] Noven [Pharmaceuticals Inc. (‘Noven’)] has presented additional prior art” like Sasaki “and declaratory evidence that was not before the [c]ourt” in that case.5 Noven II, 2015 WL 5782081, at *2. Similarly, as to Noven D. Del., the PTAB found that it did not control because the parties provided additional evidence that was not before the Delaware District Court.6 Id.; see id. at *5 (identifying as new evidence two declarations of Dr. Agis Kydonieus, two declarations of Dr. Christian Schöneich, and one declaration of Dr. Alexander M. Klibanov). Novartis tacitly concedes that the record here is different. See Appellants’ Reply 7 n.1 (“The USPTO and Noven argue that the parties submitted expert declarations and deposition testimony that was not before the Noven [D. Del.] Court. But neither disputes that these materials are substantively the same as the experts’ testimony before the Noven [D. Del.] Court.” (emphasis added) (citations omitted)), 11 (“The [PTAB] sought to explain its rejection of this [c]ourt’s Watson decision on grounds that Noven presented art and evidence in the [inter partes review] that was not before the Watson [c]ourt[]. While differences in the record could justify a different outcome overall, under Baxter, they do not support the [PTAB]’s contrary conclusions on the specific rivastigmine art and arguments previously adjudicated in Watson.” (emphasis added) (citation omitted)). It is unsurprising that different records may lead to different findings and conclusions.

Nevertheless, even if the record were the same, Novartis’s argument would fail as a matter of law. The PTAB determined that a “petitioner in an inter partes review proves unpatentability by a preponderance of the evidence (see 35 U.S.C. § 316(e)) rather than by clear and convincing evidence[] as required in district court litigation,” meaning that the PTAB properly may reach a different conclusion based on the same evidence. That position comports with recent Supreme Court precedent, which held that

[a] district court may find a patent claim to be valid, and the [USPTO] may later cancel that claim in its own review. . . . This possibility, however, has long been present in our patent system, which provides different tracks—one in the [USPTO] and one in the courts—for the review and adjudication of patent claims. As we have explained. . . , inter partes review imposes a different burden of proof on the challenger. These different evidentiary burdens mean that the possibility of inconsistent results is inherent to Congress’[s] regulatory design.

Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2146 (2016) (citation omitted). Thus, the prior decisions in Watson and Noven D. Del. did not bind the PTAB.

Celltrion Files IPR Petitions Against Genentech's Herceptin Dosing Regimen Patents

            On March 24, 2017, Celltrion filed two separate IPR petitions against Genentech’s patents covering "a method for treatment a human patient diagnosed with cancer characterized by overexpression of ErbB2 receptor.”  The patents cover the drug Herceptin (trastuzumab), and claim administering an initial dose of Herceptin, followed by subsequent doses that are “same or less than the initial dose.”

Patent/IPR	Claim 1
6,627,196 IPR2017-01139	1. A method for the treatment of a human patient diagnosed with cancer characterized by overexpression of ErbB2 receptor, comprising administering an effective amount of an anti-ErbB2 antibody to the human patient, the method comprising: administering to the patient an initial dose of at least approximately 5 mg/kg of the anti-ErbB2 antibody; and administering to the patient a plurality of subsequent doses of the antibody in an amount that is approximately the same or less than the initial dose, wherein the subsequent doses are separated in time from each other by at least two weeks.
7,371,379  IPR2017-01140	1. A method for the treatment of a human patient diagnosed with cancer characterized by overexpression of ErbB2 receptor, comprising administering an effective amount of an anti-ErbB2 antibody to the human patient, the method comprising: administering to the patient an initial dose of at least approximately 5 mg/kg of the anti-ErbB2 antibody; and administering to the patient a plurality of subsequent doses of the antibody in an amount that is approximately the same or less than the initial dose, wherein the subsequent doses are separated in time from each other by at least two weeks; and further comprising administering an effective amount of a chemotherapeutic agent to the patient.

The patents admit that the prior art trastuzumab dosing regimen consisted of a 4 mg/kg loading dose, followed by a weekly 2 mg/kg maintenance doses.  The patents claim a higher initial dose (at least 5mg/kg versus 4mg/kg) followed by a less frequent tri-weekly dose (“separated by at least two weeks”) than the admitted prior art’s more frequent weekly dose.

Celltrion’s position is that the claims of these two patents are obvious over Slamon[1] and Watanabe[2], in View of Baselga[3] and Pegram[4].  Celltrion does not have an anticipatory position.

 

Celltrion mainly relies on Slamon, which discloses administration of trastuzumab “of 8 mg/kg over the first three week period, followed by 6 mg/kg every three weeks thereafter:”

Week	1	2		3		4	5	6	7	8		9		10	11	12
Weekly dose (mg/kg)	4	2		2		2	2	2	2	2		2		2	2	2
Q 3 week dose (mg/kg)	8					6			6					6
Claims of the Patents	5 or more		0		0	Same or less as initial	0	0	Same or less as initial		0		0	Same or less as initial	0	0

According to Celltrion, “to account for an every-three-week schedule, a POSA would have administered an 8 mg/kg loading dose, followed by 6 mg/kg maintenance doses, each administered three weeks apart.”

Celltrion relies on Baselga and Pegram for disclosing pharmacokinetic data that allow POSA to calculate serum concentration since “the prior art repeatedly disclosed a target efficacious serum concentration of 10 μg/ml. . .Starting with an initial serum concentration of 169 μg/ml, and applying the conservative one week half-life discussed above, a POSA would have calculated that the serum concentration would still remain well above the 10 μg/ml target efficacious serum concentration three weeks after the 6 mg/kg dose is administered (i.e., 50% would remain after one week, 25 % after two weeks, and 12.5%, or approximately 21.1 μg/ml would remain after three weeks).”

Celltrion relies on Watanabe for disclosing “that administration of weekly doses as high as 8 mg/kg were safe and relatively well-tolerated.”

Celltrion’s petition also addresses statements by Genentech during prosecution that the prior art taught away from the claimed invention:

The applicants responded that the prior art taught away from the claimed invention because (1) a POSA would not have wanted to increase the interval between doses beyond trastuzumab’s known half-life (i.e., either 5.8, 8.3, or 9.1 days) “for fear that insufficient levels of drug would remain in the patient to treat cancer;” and (2) Watanabe recommended further studies with a 2 mg/kg or 4 mg/kg weekly dose, not a higher, less frequent dose.

Regarding Genentech’s first point on not increasing the interval between doses beyond the half-life, Celltrion argues that “half-life is only one piece of the relevant information. . . Rather, when determining whether a less frequent regimen was likely to be effective, a POSA would have considered half-life together with initial serum concentration and target trough serum concentration.”  Regarding the second point of Watanabe recommending lower doses than the claimed dose, Celltrion argues that “Watanabe was published in the same proceedings as Slamon, and there is no reason to believe that Watanabe was aware of Slamon’s results prior to its publication.  Thus, because Watanabe’s suggestion to pursue a weekly regimen was made without the benefit of Slamon’s disclosure, it is not reflective of all of the prior art available to a POSA at the time of the alleged invention.”  

The Board has not yet made a decision on the petitions.  Genentech's related patent in Europe has been found to be invalid. <http://www.kwm.com/en/uk/knowledge/insights/court-of-appeal-upholds-invalidity-of-herceptin-dosing-regime-patent-20150211>.

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[1] Trial, 17 J. CLIN. ONCOLOGY, *377, 98a (May 1998).

[2] 17 J. CLIN. ONCOLOGY, *702, 182a (May 1998)

[3] 14 J. CLIN. ONCOLOGY, No. 3 737-744 (Mar. 1996)

[4] 16 J. CLIN. ONCOLOGY, No. 8 2659-2671 (Aug. 1998)