Trastuzumab - USA

IPR decision (Jul 31, 2018):

AIA Review	Filing Date	Institution Date	Petitioner	Patent No.	Final Written Decision
IPR2017-02031	08/31/2017	03/29/2018	Boehringer Ingelheim	6,407,213	Terminated-Adverse Judgment
IPR2017-02032	08/31/2017	03/29/2018	Boehringer Ingelheim	6,407,213	Terminated-Adverse Judgment

On US’213 patent, Mylan previously filed IPRs (IPR2016-01693 & IPR2016-01694) on 08/30/2016 which were terminated due to settlement. Celltrion, Pfizer & Samsung Bioepis each filed 2 separate IPRs which were instituted by PTAB in Dec 2017 & Feb 2018.

US 6,407,213 (Genentech; Exp: Jun 18, 2019)

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.

30. An antibody which binds p185.sup.HER2 and comprises a humanized antibody variable domain, wherein the humanized antibody variable domain comprises non-human Complementarity Determining Region (CDR) amino acid residues which bind p185.sup.HER2 incorporated into a human antibody variable domain, and further comprises a Framework Region (FR) amino acid substitution at a site selected from the group consisting of: 4L, 38L, 43L, 44L, 46L, 58L, 62L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H, 39H, 43H, 45H, 69H, 70H, 74H, 75H, 76H, 78H and 92H, utilizing the numbering system set forth in Kabat.

62. A humanized antibody variable domain comprising non-human Complementarity Determining Region (CDR) amino acid residues which bind an antigen incorporated into a consensus human variable domain, and further comprising an amino acid substitution at a site selected from the group consisting of: 4L, 38L, 43L, 44L, 46L, 58L, 62L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H, 39H, 43H, 45H, 69H, 70H, 74H, 75H, 76H, 78H and 92H, utilizing the numbering system set forth in Kabat.

63. A humanized antibody which lacks immunogenicity compared to a non-human parent antibody upon repeated administration to a human patient in order to treat a chronic disease in that patient, wherein the humanized antibody comprises non-human Complementarity Determining Region (CDR) amino acid residues which bind an antigen incorporated into a human antibody variable domain, and further comprises an amino acid substitution at a site selected from the group consisting of: 4L, 38L, 43L, 44L, 46L, 58L, 62L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H, 39H, 43H, 45H, 69H, 70H, 74H, 75H, 76H, 78H and 92H, utilizing the numbering system set forth in Kabat.

64. A humanized variant of a non-human parent antibody which binds an antigen and comprises a human variable domain comprising the most frequently occurring amino acid residues at each location in all human immunoglobulins of a human heavy chain immunoglobulin subgroup wherein amino acid residues forming Complementarity Determining Regions (CDRs) thereof comprise non-human antibody amino acid residues, and further comprises a Framework Region (FR) substitution where the substituted FR residue: (a) noncovalently binds antigen directly; (b) interacts with a CDR; (c) introduces a glycosylation site which affects the antigen binding or affinity of the antibody; or (d) participates in the V.sub.L -V.sub.H interface by affecting the proximity or orientation of the V.sub.L and V.sub.H regions with respect to one another.

66. A humanized antibody heavy chain variable domain comprising non-human Complementarity Determining Region (CDR) amino acid residues which bind 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: 24H, 73H, 76H, 78H, and 93H, utilizing the numbering system set forth in Kabat.

79. A humanized variant of a non-human parent antibody which binds an antigen, wherein the humanized variant comprises Complementarity Determining Region (CDR) amino acid residues of the non-human parent antibody incorporated into a human antibody variable domain, and further comprises Framework Region (FR) substitutions at heavy chain positions 71H, 73H, 78H and 93H, utilizing the numbering system set forth in Kabat.

80. 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 where the substituted FR residue:

(a) noncovalently binds antigen directly;

(b) interacts with a CDR; or

(c) participates in the V.sub.L -V.sub.H interface by affecting the proximity or orientation of the V.sub.L and V.sub.H regions with respect to one another, and wherein the substituted FR residue is 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, 24H, 36H, 39H, 43H, 45H, 69H, 70H, 73H, 74H, 76H, 78H, 92H and 93H, utilizing the numbering system set forth in Kabat.