Bristol-Myers Squibb’s CTLA4Ig Formulation Patent Survives IPR Obviousness Challenge from Momenta Pharmaceuticals

Momenta v. BMS

January 3, 2016

MOMENTA PHARMACEUTICALS, INC. (Petitioner)
v.
BRISTOL-MYERS SQUIBB COMPANY (Patent Owner)

Case IPR2015-01537
Patent 8,476,239
FINAL WRITTEN DECISION
December 22, 2016

The PTAB concluded that the preponderance of the evidence did not support Momenta’s argument that the challenged claims would have been obvious.

The claims of Patent US 8,476,239 are directed to stable liquid formulations of the therapeutic molecule CTLA4Ig.  CTLA4Ig is a protein molecule that is used to treat immune system diseases and disorders such as rheumatoid arthritis and adverse transplant reactions.

Claim1:  A stable formulation suitable for subcutaneous administration comprising:
[1]  at least 100mg/ml CTLA4Ig molecule,
[2]  a sugar selected from the group consisting of sucrose, lactose, maltose, mannitol and trehalose and mixtures thereof and
[3]  a pharmaceutically acceptable aqueous carrier, wherein the formulation has a
[4]  pH range of from 6 to 8 and
[5]  a viscosity of from 9 to 20 cps, and
[6]  the weight ratio of sugar:protein is 1.1:1 or higher.
(Bracketed numbers added)

Momenta argued that the inventors did “nothing more than the efforts of a skilled formulator choosing from a limited set of known formulations to subcutaneous liquid formulations.” Momenta further argued that “the inventors went to the formulator’s toolbox and tried the first line of excipients and formulation parameters.  And they worked.” The PTAB agreed that the prior art references provided general guidance for formulating proteins as stable liquids and that BMS followed certain aspects of those general teachings when creating its stable liquid formulation comprising CLTA4Ig, a known protein.  Momenta’s cited evidence, however, did not persuade the PTAB that an ordinarily skilled artisan would have reasonably expected to be successful in achieving the claimed formulations. The evidence was not persuasive because, despite the prior art teaching of general guidance for formulating proteins as stable liquids, the prior art also taught that maintaining physical and chemical stabilities for most proteins in aqueous solution for an extended period is extremely difficult. Expert testimony about testimony about routine trial-and-error optimization did not overcome the statements of difficulty. Such statements of difficulty in the art indicated to the PTAB that there would not have been a reasonable expectation of success in achieving the claimed formulations.

The PTAB highlighted in the importance of anticipated success and predictable results in determining obviousness. Citing the U.S. Supreme Court:

When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.  In that instance the fact that a combination was obvious to try might show that it was obvious under § 103. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007) (emphasis added); compare Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 809 (Fed. Cir. 1989) (“Reached by means of routine procedures, and producing only predictable results, the recited dosages therefore do not distinguish the claims of the ’430 patent from the amiloride/hydrochlorothiazide combination that the district court properly found was disclosed in the ’813 patent.” (emphasis added)).

Links:

PDF of Final Decision (IPR2015-01537)

Update 1/9/2017 – Link to Jones Day Blog:
“Routine Trial-and-Error Approach to Protein Formulation Is Not Sufficient to Establish Obviousness Absent a Reasonable Expectation of Success in Achieving the Claimed Formulation”

USPTO’s Patents Ombudsman Program

Check out the USPTO’s Patents Ombudsman program:

https://www.uspto.gov/patent/ombudsman-program

“The Patents Ombudsman Program enhances the USPTO’s ability to assist applicants or their representatives with issues that arise during patent application prosecution. More specifically, when there is a breakdown in the normal application process, including before and after prosecution, the Patents Ombudsman Program can assist in getting the application back on track.”

Medgraph v. Medtronic

December 13, 2016

Precedential Opinion today from the U. S. Court of Appeals for the Federal Circuit:

MEDGRAPH, INC. v. MEDTRONIC, INC.; No. 15-2019 (Fed. Cir. Dec. 13, 2016)

The Federal Circuit panel affirmed the District Court’s dismissal of Medgraph’s claims of infringement. Earlier, the Federal Circuit en banc, in Akamai v. Limelight, broadened the law attributing third-party acts to an accused infringer to include occasions when an accused infringer “conditions participation in an activity or receipt of a benefit upon performance of a step or steps” of a claimed method. Rather than remand the case to the district court, the Federal Circuit panel said that Medgraph did not produce facts meeting even the new more broad standard.

Link to CAFC Opinion PDF:
http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/15-2019.Opinion.12-9-2016.1.PDF
Link to Finnegan’s Federal Circuit IP blog post:
“Change in Law Does Not Always Compel Remand”

Analogues of Poison Dart Frog Toxins 

C&EN’s article on Dr. Du Bois’s synthesis of (-)-Batrachotoxin caught my Eye. I once took care of a few poison dart frogs for a friend while he was travelling. Feeding them fruit flies was actually fun. Naturally I checked to see what patents have issued.

Check out: “Batrachotoxin analogues, compositions, uses, and preparation thereof”
US 9090627 B2

PTAB Upholds Ravicti® Method Claims

The Patent Trial and Appeal Board upheld US Patent 8,642,012  “Methods of Treatment Using AmmoniaScavenging Drugs” owned by Horizon Therapeutics LLC, which claims methods  for treating a patient having a urea cycle disorder using a phenylacetic acid (PAA) prodrug [Glycerol phenylbutyrate (Ravicti®)].  Par Pharmaceutical Inc. and Lupin Ltd. had challenged the claims on obviousness grounds.

PTAB Decision

Claim 1. A method of treating a patient having a urea cycle disorder comprising (a) determining a target urinary phenylacetyl glutamine (PAGN) output (b) calculating an effective initial dosage of phenylacetic acid (PAA) prodrug selected from glyceryl tri-[4phenylbutyrate] (HPN-100) and phenylbutyric acid (PBA) or a pharmaceutically acceptable salt of PBA, wherein the effective dosage of PAA prodrug is calculated based on a mean conversion of PAA prodrug to urinary PAGN of about 60%; and (c) administering the effective initial dosage of PAA prodrug to the patient.

 

 

Subject Matter Eligibility of a Chemical Process

The USPTO, provides an example of a patent-eligible claim for a process of hydrolyzing fat molecules into free fatty acids and glycerol without using conventional methods (at the time of invention) of steam distillation with lye or sulfuric acid. [May, 2016]

May 2016 Update: Subject Matter Eligibility Examples: Life Sciences (May 6, 2016)

Example 33 “Hydrolysis of Fat” – From the USPTO’s Subject Matter Eligibility Examples: Life Sciences

The USPTO based the following “patent eligible” claim on technology from US Patent 11,766, which was upheld by the Supreme Court in Tilghman v. Proctor, 102 U.S. 707 (1881).  Although the case is very old, the USPTO notes that Supreme Court has subsequently described the decision as upholding the eligibility of process claims containing a law of nature. See, e.g., Parker v. Flook, 437 U.S. 584, 590-91 and n.12 (1978); Gottschalk v. Benson, 409 U.S. 63, 70 (1972).

Claim    1.   A process for obtaining free fatty acids and glycerol from fat comprising:

(a) mixing substantially equal quantities of fat and water in a closed vessel; and

(b) heating the mixture to an elevated temperature of at least 600 degrees Fahrenheit under sufficient pressure to prevent the formation of steam in the closed vessel; and maintaining the elevated temperature for at least 10 minutes.

USPTO Analysis

Although the claim is founded upon a chemical principle relating to neutral fats, the claim is eligible because, it is not attempting to tie up the chemical principal so that others cannot practice it.  Even if the claim were directed to a judicial exception, the claim amounts to something “significantly more” than any exception.  The claim would amount to something “significantly more” because the claim recites specific unconventional steps.

Patenting Azole-Based Fungicides to Protect Bananas

Chemical & Engineering News (C&EN) published a news update about a 57% increase in patent activity over the past 5 years for fighting fungal wilt known as Panama disease.  Chemical Abstracts Service searched the HCAplus database on STN with a result of 510 patents since 2010 that mention Fusarium oxysporum. C&EN notes that Azole-based fungicides continue to dominate the fight and included BASF patent application publication WO 2015/181009 as an example.

“New Weapons in the Fight against Fungal Wilt”

Chemical & Engineering News, Vol. 44, page 11, November 7, 2016.

http://cen.acs.org/articles/94/i43/New-weapons-fight-against-fungal.html

Do Inventors Need to Know “Why” Their Inventions Work? No.

To obtain a valid patent, does an inventor need to know why his invention works? Hal Wegner reminds us in his blog that the answer is “no.”

Wegner’s Writings

Going back a bit to 1911, the Supreme Court in Diamond Rubber stated:

“A patentee may be baldly empirical, seeing nothing beyond his experiments and the result ***. It is certainly not necessary that [the inventor] understand or be able to state the scientific principles underlying his invention ***.”

Diamond Rubber Co. v. Consol. Rubber Tire Co., 220 U.S. 428, 435–36 (1911) (citations omitted)

Example for Organic Chemist Inventors:

If you have invented a new compound, the new compound must be “useful.”  You may still be able to get a patent on it even if you haven’t nailed down its mechanism of action.  You may show that is useful in an enzymatic assay.  But you do not need to prove exactly how or where the molecule binds to the target enzyme.

USPTO-Proposed Rule for Recognizing Privileged Communications Between Clients and Non-Attorney Patent Agents and Forgein Patent Practitioners

The United States Patent and Trademark Office (USPTO) published a proposed rule for recognizing privileged communications between clients and non-attorney patent agents and forgein patent practitioners at the Patent Trial and Appeal Board (PTAB).

Link to Federal Register

This new rule, however,  will not affect the duty of disclosure and candor before the Office under 37 CFR 1.56.

The Office is soliciting comments from the public on this proposed rulemaking. Written comments must be received on or before December 19, 2016 to ensure consideration.

 

US Supreme Court Denied Certiorari in Amphastar v. Momenta (No. 15-1402)

The Amphastar case is concerned with the § 271(e)(2) Hatch-Waxman “safe harbor.”

35 U.S.C. § 271(e)(1)  [Hatch-Waxman Act safe harbor] states that it “shall not be an act of infringement to … use … a patented invention … solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs[.]”

Amphastar and others petitioned the Supreme Court on May 17, 2016 presenting the  question: “Whether the safe harbor protects a generic drug manufacturer’s bioequivalence testing that is performed only as a condition of maintaining FDA approval and is documented in records that must be submitted to the FDA upon request.”

The Supreme Court denied Certiorari on October 3, 2016. [Order List]

Amphastar argued that the US Court of Appeals for the Federal Circuit (CAFC) interpreted the Safe Harbor provision of  § 271(e)(1) too narrowly.  The CAFC denied Amphastar safe harbor immunity from Momenta’s patent covering the only approved test for showing bioequivalence of Lovenox.

Amphastar Pharmaceuticals, Inc., et al. v. Momenta Pharmaceuticals, Inc., et al., No. 15-1402

—————————————

 http://www.laipla.net/amphastar-v-momenta-supreme-court-denies-certiorari/

Amphastar Argues To Supreme Court: Hatch-Waxman Patent Safe Harbor Is Too Narrow [Lexis Legal News 9/1/2016]

Battle of Lovenox Generics Brought to Supreme Court [Bloomberg BNA 5/20/2016]

Cert. Petition:No. 15-1402 (May 17, 2016)

Panel decision:809 F.3d 610 (Fed. Cir. Nov. 10, 2015)

U.S. Patent:No. No. 7,575,886

 

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