Genentech's Herceptin Patents Asserted Against Samsung Bioepis

Genentech and the City of Hope filed a patent infringement lawsuit against Samsung Bioepis over Bioepis’ biosimilar version of Herceptin.  (1:18-cv-01363-CFC).  The plaintiffs allege that “Bioepis did not disclose all of the information relevant to establishing whether the manufacture of Bioepis’s aBLA product will infringe each of the patents identified on Genentech’s Apr. 23, 2018 list, despite Genentech’s request that Bioepis provide sufficient ‘other information that describes the process or processes used to manufacture” as required by 42 U.S.C. § 262(l)(A).  Bioepis’s failure to provide sufficient information under those circumstances supports Genentech’s contention that manufacturing Bioepis’s aBLA product will infringe such patents.’”  The plaintiffs assert the following patents in the first amended complaint filed on January 17, 2019:

Method for Making Humanized Antibodies
6,407,213	1. A humanized antibody variable domain comprising non-human Complementarity Determining Region (CDR) amino acid residues which bind an antigen incorporated into a human antibody variable domain, and further comprising a Framework Region (FR) amino acid substitution at a site selected from the group consisting of: 4L, 38L, 43L, 44L, 58L, 62L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H, 39H, 43H, 45H, 69H, 70H, 74H, and 92H, utilizing the numbering system set forth in Kabat.
The Combination Chemotherapy Patents
7,846,441	1. A method for the treatment of a human patient with a malignant progressing tumor or cancer characterized by overexpression of ErbB2 receptor, comprising administering a combination of an intact antibody which binds to epitope 4D5 within the ErbB2 extracellular domain sequence and a taxoid, in the absence of an anthracycline derivative, to the human patient in an amount effective to extend the time to disease progression in said human patient, without increase in overall severe adverse events.
7,892,549	1. A method for the treatment of a human patient with breast cancer that overexpresses ErbB2 receptor, comprising administering a combination of an antibody that binds ErbB2, a taxoid, and a further growth inhibitory agent to the human patient in an amount effective to extend the time to disease progression in the human patient, wherein the antibody binds to epitope 4D5 within the ErbB2 extracellular domain sequence.
The Cabilly Patents
6,331,415	1. A process for producing an immunoglobulin molecule or an immunologically functional immunoglobulin fragment comprising at least the variable domains of the immunoglobulin heavy and light chains, in a single host cell, comprising the steps of: (i) transforming said single host cell with a first DNA sequence encoding at least the variable domain of the immunoglobulin heavy chain and a second DNA sequence encoding at least the variable domain of the immunoglobulin light chain, and (ii) independently expressing said first DNA sequence and said second DNA sequence so that said immunoglobulin heavy and light chains are produced as separate molecules in said transformed single host cell.
7,923,221	1. A method for making an antibody heavy chain or fragment thereof and an antibody light chain or fragment thereof each having specificity for a desired antigen, wherein the heavy chain or fragment thereof comprises a human constant region sequence and a variable region comprising non human mammalian variable region sequences, the method comprising culturing a recombinant host cell comprising DNA encoding the heavy chain or fragment thereof and the light chain or fragment thereof and recovering the heavy chain or fragment thereof and light chain or fragment thereof from the host cell culture.
The Method of Administration Patents
6,627,196	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	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.
10,160,811	1. A method for the treatment of a human patient diagnosed with breast cancer characterized by 2+ or 3+ overexpression of ErbB2 receptor as determined by immunohistochemistry or fluorescence in situ hybridization (FISH), comprising the steps of administering to the patient an initial dose of 8 mg/kg of anti-ErbB2 huMAb 4D5-8 antibody; and administering to the patient a plurality of subsequent doses of 6 mg/kg of the antibody, wherein all doses are separated in time from each other by three weeks.
The Acidic Variants Patents
6,339,142	1. A composition comprising a mixture of anti-HER2 antibody and one or more acidic variants thereof, wherein the amount of the acidic variant(s) is less than about 25%.
6,417,335	1. A method for purifying an antibody from a composition comprising the antibody and a contaminant, which method comprises: (a) loading the composition onto a cation exchange resin, wherein the amount of antibody loaded onto the cation exchange resin is from about 20 mg to about 35 mg of the antibody per mL of cation exchange resin; and (b) eluting the antibody from the cation exchange resin.
9,249,218	1. A therapeutic composition comprising a mixture of anti-HER2 antibody and one or more acidic variants thereof, wherein the amount of the acidic variant(s) is less than about 25%, and wherein the acidic variant(s) are predominantly deamidated variants wherein one or more asparagine residues of the anti-HER2 antibody have been deamidated, and wherein the anti-HER2 antibody is humMAb4D5-8, and wherein the deamidated variants have Asn30 in CDR1 of either or both V.sub.L regions of humMAb4D5-8 converted to aspartate, and a pharmaceutically acceptable carrier.
HER2 Diagnostic Patents
7,993,834	1. A method for increasing likelihood of effectiveness of breast cancer treatment with humanized anti-ErbB2 antibody huMAb4D5-8, which method comprises administering a cancer treating dose of said antibody to a human subject diagnosed with breast cancer, wherein an erbB2 gene amplification in breast cancer cells in a tissue sample from the subject has been detected, and wherein the breast cancer cells from the human subject have been found to have a 0 or 1+ score of ErbB2 protein expression by immunohistochemistry.
8,076,066	1. A method of identifying and treating a breast cancer patient disposed to respond favorably to a HER2 antibody, huMAb4D5-8, which method comprises detecting her2 gene amplification in cancer cells in a breast tissue sample from the patient and treating the patient with her2 gene amplification with the HER2 antibody in an amount effective to treat the breast cancer, wherein the patient's cancer cells express HER2 at a 0 or 1+ level by immunohistochemistry.
8,440,402	1. A method for identifying and treating a patient disposed to respond favorably to a HER2 antibody, huMAb4D5-8, for treating breast cancer, which method comprises detecting her2 gene amplification in tumor cells in a tissue sample from the patient and treating the patient with her2 gene amplification with the HER2 antibody in an amount effective to treat the breast cancer, wherein the patient's tumor cells express HER2 at a 0 or 1+ level by immunohistochemistry.
Cell Culture, Purification, and Antibody Manufacturing Patents
6,610,516	1. A process for producing a human glycoprotein having multiple glycoforms, comprising culturing Chinese hamster ovary cells expressing nucleic acid encoding said glycoprotein in a serum-free medium in a production phase at a temperature of about 30C. to 35C. and in the presence of about 0 to 2 mM of a butyrate salt, wherein the process produces an increased percentage of glycoprotein molecules having one glycoform relative to an identical process performed at 37C. in the absence of butyrate.
7,390,660	1. A method for reducing glucose consumption during cultivation of CHO, myeloma, or hybridoma cells, comprising cultivating CHO, myeloma, or hybridoma cells in culture medium in the presence of citric acid or citrate wherein said citric acid or citrate is maintained at a concentration of about 1 to 50 mmol/l during cultivation and wherein said citric acid or citrate is not bound in a chelate complex with iron or another transition metal ion.
7,485,704	1. A method of purifying a protein which comprises a CH2/CH3 region comprising: a. subjecting a composition comprising said protein to protein A affinity chromatography to provide a recovered composition and measuring leached protein A in said recovered composition; and b. if greater than about 20 ng protein A per mg of said protein is measured in said recovered composition, then performing subsequent purification of compositions comprising said protein by protein A affinity chromatography at a temperature in the range from about 3C. to about 18C., such that protein A leaching is reduced.
7,807,799	1. A method of purifying a protein which comprises a CH2/CH3 region, comprising subjecting a composition comprising said protein to protein A affinity chromatography at a temperature in the range from about 10C. to about 18C.
8,512,983	1. A process for producing a polypeptide in a mammalian host cell expressing said polypeptide, comprising culturing the mammalian host cell in a production phase of the culture in a glutamine-free production culture medium containing asparagine, wherein the asparagine is added at a concentration in the range of 7.5 mM to 15 mM.
8,574,869	1. A method for the prevention of the reduction of a disulfide bond in an antibody expressed in a recombinant host cell, comprising, following fermentation, sparging the pre-harvest or harvested culture fluid of said recombinant host cell with air, wherein the amount of dissolved oxygen (dO2) in the pre-harvest or harvested culture fluid is at least 10%.
9,714,293	1. A process for producing a polypeptide in a host cell expressing said polypeptide, comprising culturing the host cell in a production phase of the culture in a glutamine-free production culture medium containing asparagine and aspartic acid, wherein the asparagine is added at a concentration in the range of 7.5 mM to 15 mM and wherein the aspartic acid is added at a concentration in the range of 1 mM to 10 mM.

Patent term adjustment went beyond the period during which the applicant failed to undertake reasonable efforts

SUPERNUS PHARMACEUTICALS, INC v. IANCU

A plain reading of the statute shows that Congress imposed two limitations on the amount of time that the USPTO can use as applicant delay for purposes of reducing PTA. First, the statute expressly requires that any reduction to PTA be equal to the period of time during which an applicant fails to engage in reasonable efforts. Second, the statute expressly ties reduction of the PTA to the specific time period during which the applicant failed to engage in reasonable efforts.

The PTA statute requires that any PTA reduction be equal to the period of time during which an applicant fails to engage in reasonable efforts. The word “equal” is widely understood to mean “the same in amount, number, or size.” E.g., Equal, Cambridge Dictionary of American English 287 (2000). Stated differently, PTA reduction cannot exceed the period of time during which an applicant failed to engage in reasonable efforts. Thus, if there is no period of time during which the applicant could have but failed to engage in reasonable efforts, there can be no reduction to the PTA.





http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/17-1357.Opinion.1-23-2019.pdf

Supreme Court: AIA Did Not Change Meaning Of On-Sale Bar

HELSINN HEALTHCARE S. A. v. TEVA PHARMACEUTICALS USA, INC.

Every patent statute since 1836 has included an on-sale bar. The patent statute in force immediately before the AIA prevented a person from receiving a patent if, “more than one year prior to the date of the application for patent in the United States,” “the invention was . . . on sale” in the United States. 35 U. S. C. §102(b) (2006 ed., Supp. IV). The AIA, as relevant here, retained the on-sale bar and added the catchall phrase “or otherwise available to the public.” §102(a)(1) (2012 ed.) (“A person shall be entitled to a patent unless” the “claimed invention was . . . in public use, on sale, or otherwise available to the public . . . ”). We must decide whether these changes altered the meaning of the “on sale” bar. We hold that they did not.

https://www.supremecourt.gov/opinions/18pdf/17-1229_2co3.pdf

A generic pharma company had standing to appeal PTAB's decision in an IPR

Federal Circuit:

We agree with Amerigen that it has standing to appeal from the Board’s decision because the launch of its tentatively approved drug is blocked by the ’650 patent, and invalidation of the patent would advance its drug’s launch. The ’650 patent is listed in the FDA’s “Orange Book”12 entry for Toviaz®. Amerigen has a Paragraph III certification for the ’650 patent,13 which means that the FDA will only approve Amerigen’s ANDA after the ’650 patent has expired. 21 U.S.C. § 355(j)(5)(B)(ii). However, if the ’650 patent is held unpatentable through reversal of the Board’s decision, then the New Drug Application (“NDA”) holder14 must “promptly notify” the FDA that the patent “no longer meet[s] the statutory requirements for listing.” 21 C.F.R. § 314.53(f)(2)(i). And § 314.53 expressly states that a patent does not meet the requirements for listing “if there has been a judicial finding of invalidity for a listed patent, from which no appeal has been or can be taken.” Id. After a notification from the NDA holder that a patent may no longer be listed, the FDA “will remove a patent . . . from the list if there is no first applicant eligible for 180–day exclusivity based on a paragraph IV certification to that patent or after the 180–day exclusivity period of a first applicant based on that patent has expired or has been extinguished.” Id.


http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/17-2596.Opinion.1-11-2019.pdf

Proposed Amendment Bans IPRs for Generics and Biosimilars

https://www.hatch.senate.gov/public/_cache/files/7fda71ea-a175-4a93-9d62-d3bf801a70e9/EHF18270.pdf

https://www.hatch.senate.gov/public/index.cfm/releases?ID=4D895DB2-0F0C-4023-A2AB-7771166AFF00

Senator Orrin Hatch (R-UT), the Chairman of the Senate Republican High-Tech Task Force and co-author of the Hatch-Waxman Act, delivered the following remarks at the Senate Judiciary Committee hearing.  

Thank you, Mr. Chairman. I appreciate your efforts on this bill. As the co-author of Hatch-Waxman, I have a keen interest in ensuring that we have a well-functioning generic drug industry. For that to happen, generics need to be able to obtain access to samples so they can conduct the tests and research necessary to achieve bioequivalency. 

The CREATES Act has a laudable goal. But I don’t believe it strikes the right balance as currently written, and so I will be voting no today. In particular, I believe the damages cap in the bill far exceeds what is necessary to ensure adequate deterrence and could incentivize non-meritorious litigation.

I’d also like to take a moment to discuss the amendment I circulated. I’ve titled this amendment the Hatch-Waxman Integrity Act. 

I mentioned earlier that as the co-author of Hatch-Waxman, I have a keen interest in ensuring we have a well-functioning generic drug industry. Well, there are two sides to that coin. One is ensuring that generic companies are able to develop drugs. The other is ensuring that brand companies have sufficient protections in place to recoup their investments. It won’t do to give generics the ability to develop and market low-cost medications if brand companies don’t have the incentive to create those medications in the first place. And so Hatch-Waxman struck a careful balance, one that has endured for decades.

But it’s recently come to my attention that the inter partes review, or IPR, process that this committee created in the America Invents Act, and which I strongly support, is producing unintended consequences in the Hatch-Waxman context.  

IPR is a critical tool for fighting patent trolls and is of particular importance to the tech community. But it also threatens to upend the careful Hatch-Waxman balance by enabling two separate paths to attack a brand patent.  

First is Hatch-Waxman litigation, which contains numerous carefully calibrated requirements affecting timing, market exclusivity, and FDA approval. Second is IPR, which is a much blunter instrument than Hatch-Waxman and which contains none of the important industry-specific balancing features that come into play in Hatch-Waxman litigation.

I want to be clear that I strongly support IPR. But I do not support its use in a way that upends or eviscerates Hatch-Waxman.

And so I’ve circulated an amendment that would force a party that wishes to challenge a brand patent to choose: the party can file a Hatch-Waxman suit, which carries the benefits of being able to rely on the brand company’s safety and efficacy studies for FDA approval, or it can file an IPR proceeding, which is cheaper, faster, and easier to win. But it can’t do both.

My amendment would preserve Hatch-Waxman as the standard path for generic companies to challenge brand patents, while keeping IPR as an option in situations where other interests come into play. But it would prevent companies from using IPR to put added litigation pressure on innovators above and beyond what Hatch-Waxman already provides. And it would prevent a company that rightfully loses a Hatch-Waxman suit from getting a second bite at the apple. 

I would note as well that for purposes of symmetry, the amendment also applies to post-grant review and to biologics. It will not have any impact on the use of IPR by the tech community.

I won’t be offering my amendment today because it goes beyond the scope of CREATES. But I wanted to discuss it today because it touches on issues that tie back directly to the purpose of CREATES and because it will be a top priority for me during my remaining months in office.

IMRALDI™, Biogen’s Adalimumab Biosimilar Referencing Humira®, Is Launched in the European Union

https://www.nasdaq.com/press-release/imraldi-biogens-adalimumab-biosimilar-referencing-humira-is-launched-in-the-european-union-20181017-00050

Gilead AIDS Patent Question Before the Supreme Court

In the context of patent cases involving pharmaceutical products, does the “actual controversy” requirement of the Declaratory Judgment Act, 28 U.S.C. § 2201(a), require a party seeking to introduce a generic drug product to file an application for FDA approval of that generic drug product before it can file suit for declaratory relief for patent invalidity?

https://www.aidshealth.org/wp-content/uploads/2018/08/36429-cert-petition.pdf