Patent application EP16168617A (EP), filed 2016-05-06
Publication number: EP3241845A1
Title: HUMANIZED ANTI-IL-1R3 ANTIBODIES
Abstract: [0001]    The disclosure describes humanized anti IL1RAP antibodies (Interleukin "1" receptor accessory protein, IL1R3). Several combinations of different CDRs are claimed. The antibodies can be used in cancer therapy. Examples are provided for 17 humanized antibodies (see Figures 2-4), with the following internal names : MAB-16-0015, MAB-16-0019, MAB-16-0021, MAB-16-0004, MAB-16-0009, MAB-16-0027, MAB-16-0030, MAB-16-0040, MAB-16-0043, MAB-16-0046, MAB-16-0049, MAB-16-0028, MAB-16-0031, MAB-16-0041, MAB-16-0036, MAB-16-0045, MAB-16-0048. Said antibodies inhibit IL-1R3 induced NFkB activity. They also inhibit IL-1alpha, IL-1beta, IL-33, and/or IL-36 stimulated NFkB activity.
IPC codes: C07K  16/    28            A I
Claims: number: 1
text: Humanized antibody that specifically binds to IL-1R3 or a fragment or derivative thereof that contains at least a portion of said antibody that is sufficient to confer IL-1R3 binding specificity, comprising:
number: 2
text: Humanized antibody that specifically binds to(IL-1R3 or a fragment or derivative thereof, wherein the antibody comprises a heavy chain variable (VH) region that is at least 90 % identical to a VH region selected from the group consisting of VH regions of SEQ ID NO: 1 to 34.
number: 3
text: Humanized antibody that specifically binds to IL-1R3 or a fragment or derivative thereof, wherein the antibody comprises a light chain variable (VL) region that is at least 90% identical to a VL region selected from the group consisting of VL regions of SEQ ID NO: 35 to 68.
number: 4
text: Humanized antibody that specifically binds to IL-1R3 or a fragment or derivative thereof according to claim 2, wherein the antibody comprises a heavy chain variable region (VH) comprising an amino acid sequence selected from the group of SEQ ID NO: 1 to 34.
number: 5
text: Humanized antibody that specifically binds to IL-1R3 or a fragment or derivative thereof according to claim 3, wherein the antibody comprises a light chain variable region (VL) comprising an amino acid sequence selected from the group of SEQ ID NO: 35 to 68.
number: 6
text: Humanized antibody according to any of claims 1 to 5, that specifically binds to IL-1R3, or a fragment or derivative thereof, comprising a VH region and a VL region comprising the respective CDR1, CDR2 and CDR3 regions of an antibody selected from the group consisting of MAB-15-0139, MAB-15-0106, MAB-15-0108, MAB-15-0110, MAB-15-0117, MAB-15-0121, MAB-15-0140, MAB-15-0115, MAB-15-0125, MAB-15-0119, MAB-15-0109, MAB-15-0097, MAB-15-0135, MAB-15-0133, MAB-15-0107, MAB-15-0128, MAB-15-0116, MAB-16-0004, MAB-16-0009, MAB-16-0028, MAB-16-0031, MAB-16-0043, MAB-16-0049, MAB-16-0045, MAB-16-0040, MAB-16-0036, MAB-16-0046, MAB-16-0030, MAB-16-0021, MAB-16-0019, MAB-16-0015, MAB-16-0027, MAB-16-0048, MAB-16-0041.
number: 7
text: Humanized antibody that specifically binds to IL-1R3, or a fragment or derivative thereof that contains at least a portion of said antibody that is sufficient to confer IL-1R3 binding specificity, and inhibits IL-1R3 induced NFkB activity.
number: 8
text: Humanized antibody, fragment or derivative thereof according to any of the previous claims, wherein said antibody binds to the same epitope as an antibody selected from the group of antibodies MAB-15-0139, MAB-15-0106, MAB-15-0108, MAB-15-0110, MAB-15-0117, MAB-15-0121, MAB-15-0140, MAB-15-0115, MAB-15-0125, MAB-15-0119, MAB-15-0109, MAB-15-0097, MAB-15-0135, MAB-15-0133, MAB-15-0107, MAB-15-0128, MAB-15-0116, MAB-16-0004, MAB-16-0009, MAB-16-0028, MAB-16-0031, MAB-16-0043, MAB-16-0049, MAB-16-0045, MAB-16-0040, MAB-16-0036, MAB-16-0046, MAB-16-0030, MAB-16-0021, MAB-16-0019, MAB-16-0015, MAB-16-0027, MAB-16-0048, MAB-16-0041.
number: 9
text: Humanized antibody according to any of the previous claims, wherein said antibody inhibits IL-1alpha, IL-1beta, IL-33, and/or IL-36 stimulated NFkB activity.
number: 10
text: Humanized antibody according to of the previous claims, wherein said antibody inhibits NFkB activity stimulated by a complex selected from the group consisting of IL-1β/IL-1R1/IL-1RAcP, IL-1α/IL-1R1/IL-1RAcP IL-33/ST2/IL-1RAcP, and/or IL-36/lI-36R/lL-1RAcP.
number: 11
text: Humanized IgG1LALA antibody according to of the previous claims, wherein said antibody inhibits in a concentration of 10 µg/ml NFkB expression in A549-NFkB-RE-Luc cell lysates stimulated with 0.1 ng/ml human IL-1alpha, human IL-1beta, IL-33 and/or IL-36, for 50% or more, preferably for 60% or more, preferably for 70% or more, preferably for 80% or more, preferably for 90% and more, and more preferably for 95% or more, related to the same assay without said antibody according to the invention.
number: 12
text: Humanized antibody according to of the previous claims, wherein said antibody inhibits IL-1alpha, IL-1beta, IL-33, and/or IL-36, respectively, stimulated luciferase activity in HEK293T/17 cells transfected with luciferase under control of NF-kB reporter gene.
number: 13
text: Humanized antibody according to any of the previous claims, wherein said antibody comprises at least amino acid substitutions at L234A and L235A of the human IgG1 Fc region or S228P and L235E of the human IgG4 Fc region.
number: 14
text: Humanized antibody according to any of the previous claims for the use in treating a IL-1R3 mediated disease.
number: 15
text: Humanized antibody according to claim 14, wherein the IL-1R3 mediated disease is selected from the group consisting of lung cancer, non-small cell lung (NSCL) cancer, bronchioloalviolar cell lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, gastric cancer, colon cancer, breast cancer, or uterine cancer.
number: 16
text: A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody according to any one of the preceding claims.
number: 17
text: Pharmaceutical composition according to claim 16 for the use in treating a IL-1R3 mediated disease.
number: 18
text: Pharmaceutical composition according to claim 16 or 17, wherein the IL-1R3 mediated disease is selected from the group consisting of lung cancer, non-small cell lung (NSCL) cancer, bronchioloalviolar cell lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, gastric cancer, colon cancer, breast cancer, or uterine cancer.
Office action: search_report, dated 2017-11-08
Rejection reasons: novelty_epc_54
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Final disposition: pending (2017-11-08)