Thursday, August 25, 2016

Teva loses on 40mg Copaxone (for MS) at PTAB noted a PTAB ruling on some of Teva's Copaxone patents:

Teva Pharmaceutical Industries Ltd. today [August 24, 2016] confirmed the Patent Trial and Appeal Board (PTAB) decisions from an Inter Partes Review (IPR) to invalidate all claims of the ‘250 and ‘413 patents for 40 mg COPAXONE® (glatiramer acetate injection). Teva plans to appeal to the United States Court of Appeals for the Federal Circuit


The demise of claims in the '250 patent [US Patent 8,232,250 to Ety Klinger, which is a continuation of US 8,399,413] was based on obviousness; from the final written decision in IPR2015-00643:

In sum, upon considering the evidence as a whole, we determine that the combination of Pinchasi and the 1996 SBOA teaches or suggests each limitation of claims 1 and 19, that a person of ordinary skill in the art would have had a reason to combine the references and would have had a reasonable expectation of success in dosing 40 mg GA three times over a seven-day period.

One notes that the use of the SBOA [ Summary Basis of Approval (“SBOA”) for the New Drug Application for 20 mg daily Copaxone ® (NDA #20-622) ] amounted to the use of Teva's information against Teva. [ PTAB noted: the 1996 SBOA was publicly accessible at least by July 17, 2007, more than one year before the earliest possible priority date of the ’250 patent (i.e., August 20, 2008) ] The other key reference was Irit Pinchasi, WO 2007/081975 A2, published July 19, 2007. Pinchasi was mentioned in a 2011 post at Law360 as a former Teva scientist [ ].

Of some importance to the outcome was the use of a REVIEWER COMMENT in the SBOA: a reviewer of the 1996 SBOA “recommend[ed] that [Teva] evaluate the necessity of daily [subcutaneous] injections as opposed to more infrequent intermittent administration of the drug.” Id. at 43 (citing Ex. 1007, 252).
And later in the written decision: the 1996 SBOA must still be read in the context of the prior art as a whole, which suggested less frequent dosing of GA was desirable. See In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986

Of some relevance to a different PTAB matter involving Kyle Bass, in which PTAB dismissed the significance of MRI in evaluating disease-modifying MS treatments, note the text:

In particular, we credit the testimony of Dr. Green, who notes that Pinchasi demonstrates increased efficacy with 40 mg GA when compared to 20 mg GA with no significant difference in side effects. Ex. 1004 ¶¶ 61, 95, 99. Indeed, Pinchasi concludes: The increased efficacy observed with 40 mg/day GA in reducing MRI-measured disease activity and relapse rate indicates that it is well tolerated and can improve the treatment of RRMS patients. The improvement in efficacy, however, is not accompanied by a corresponding increase of adverse reactions which would be expected upon a doubling of the administered dose.

One notes an interesting position taken by Teva:

Patent Owner argues that a person of ordinary skill in the art would not have used 40 mg of GA because a later phase III clinical trial (the “FORTE trial”) demonstrated that 40 mg of GA was not more effective than 20 mg of GA, and 40 mg of GA was associated with more frequent adverse events. PO Resp. 17–20. Upon considering the evidence as a whole, we are not persuaded. The FORTE trial found that “the 40 mg dose did not demonstrate increased efficacy in reducing the relapse rate.” Ex. 2001, 1 (emphasis added). At the same time, however, it noted that “the higher [40 mg] dose maintained the favorable safety and tolerability profile of COPAXONE® 20mg.”

PTAB brought up "teaching away" issues:

Because nothing in FORTE criticizes, discredits, or discourages the use of 40 mg of GA, we determine that FORTE does not teach away from the use of 40 mg of GA.
See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) (finding “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed”

Obsolete technology arose: In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991) (“[A] reference which disclosed obsolete technology remained in the prior art. This court considered the reference for what it disclosed in relation to the claimed invention.”)

As to predictability: we keep in mind that an obviousness inquiry does not require absolute predictability. In re Longi, 759 F.2d 887, 896 (Fed. Cir. 1985). Indeed, as the Federal Circuit has explained, simply because the formation and properties of a new drug must be verified through testing does not mean that the formulation would have not been obvious, “since the expectation of success need only be reasonable, not absolute.”
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007)

**Back on Jan. 28, 2014, Teva Pharmaceutical Industries Ltd.announced that the U.S. Food and Drug Administration (FDA) has approved the Company’s supplemental new drug application (sNDA) for three-times-a-week COPAXONE® 40mg/mL, a new dose of COPAXONE®.


And, one year ago, in August 2015, FiercePharma had written:

What does that mean for Teva? A review of the third patent is likely on the way, and "the odds of invalidation in this case are close to even," Ronny Gal wrote.

That's not great news to Teva, which scrambled to convert 70% of its patient pool over to the successor drug as it awaited word on the fate of original Copaxone. After a lower court dismissed the drug's patents, Teva scored a Supreme Court victory--only to see the case remanded and recently decided again in its rivals' favor.

Now, if Teva does lose its patents, Momenta --which developed the Sandoz knockoff--will "very likely" win FDA approval on a 40 mg generic by January 2017, the point at which copycats can legally enter the market, Gal figures. And the "critical question," as he sees it, is how many of the other four generic filers will get their own green lights and enter the market at the same time.

Whatever happens with Copaxone, though, Teva's in a better spot now than it was when the franchise first encountered IP trouble. Recently, it inked a $40.5 billion pact to buy Allergan's generics business, leaving it less reliant on the MS star. The way Gal sees it, the downside is "limited" for the company; "Teva earnings will trough at $50 in 2017, and the company has a reasonable growth trajectory from there," he wrote.


[The US Supreme Court case concerned the 20mg dose.]

Related to US 8,969,302 see IPR2015-00830:


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