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.