Patent application EP19172399A (EP), filed 2019-05-02
Publication number: EP3733708A1
Title: IMMUNE CHECKPOINT MOLECULE INHIBITOR
Abstract: The present invention provides a bispecific binding protein comprising a first and second functional moiety, each having binding affinity for a different epitope located on the same immune checkpoint molecule, for example, PD-1, PD-L1, CTLA-4 and CD47. Also provided is a pharmaceutical composition comprising the bispecific binding protein of the invention for use in therapy, particularly for use in the treatment of cancer and infectious disease.
IPC codes: A61P  35/    00            A I
C07K  16/    28            A I
Claims: number: 1
text: A bispecific binding protein comprising a first functional moiety and a second functional moiety each having binding affinity for an immune checkpoint molecule, wherein the first functional moiety and the second functional moiety are connected, and wherein the first functional moiety and the second functional moiety bind to different discrete epitopes on the surface of the same immune checkpoint molecule.
number: 2
text: The bispecific binding protein of claim 1, wherein binding affinity is for the immune checkpoint molecule PD-1, PD-L1, LAG-3, CD47 or CTLA-4, preferably wherein the immune checkpoint molecule is PD-1.
number: 3
text: The bispecific binding protein of any preceding claim, wherein the first functional moiety and the second functional moiety are connected by a peptide linker, preferably wherein the linker is 5-100 amino acid residues in length, preferably 8 to 30 amino acids residues in length, more preferably 10 to 17 amino acid residues in length.
number: 4
text: The peptide linker of claim 3, wherein the peptide linker comprises the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence having greater than 60 % homology to said amino acid sequence.
number: 5
text: The bispecific binding protein of claims 1 to 4, wherein the first functional moiety and the second functional moiety are connected by paired fusion tags, preferably wherein the paired fusion tags are a leucine zipper or an immunoglobulin Fc tag.
number: 6
text: The bispecific binding protein of any preceding claim, wherein the bispecific binding protein is a bispecific antibody or a functional fragment thereof.
number: 7
text: The bispecific binding protein of claim 6, wherein the first functional moiety and the second functional moiety comprise a fragment antigen binding (Fab) fragment, a single-chain variable fragment (scFv), an affimer or equivalent protein-binding protein, or a single-domain antibody (sdAb), preferably wherein the first functional moiety and the second functional moiety are each a single-domain antibody.
number: 8
text: The bispecific binding protein of claims 1-5, wherein the bispecific binding protein further comprises an Fc fusion tag comprising the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence having greater than 60 % homology to said amino acid.
number: 9
text: The bispecific binding protein of any preceding claim comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 11 or an amino acid sequence having greater than 60 % homology to said amino acid sequence.
number: 10
text: The bispecific binding protein of any preceding claim, wherein the first functional moiety comprises the amino acid sequence of SEQ ID NO: 2 and the second functional moiety comprises the amino acid sequence of SEQ ID NO: 3, or an amino acid sequence having greater than 60 % homology to said amino acid sequences.
number: 11
text: The bispecific binding protein of any preceding claim, wherein the first functional moiety comprises the CDR amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 and the second functional moiety comprises the CDR amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or an amino acid sequence having greater than 60 % homology to said amino acid sequences.
number: 12
text: A nucleic acid encoding the bispecific binding protein of claims 1-11, or a complementary sequence thereof.
number: 13
text: An expression vector comprising the nucleic acid of claim 12, or a host cell or cell free expression system comprising said expression vector.
number: 14
text: The bispecific binding protein according to any of claims 1-11, for use in therapy.
number: 15
text: A pharmaceutical composition comprising the bispecific binding protein, nucleic acid, vector or host cell according to any one of claims 1-14, wherein the composition additionally includes a pharmaceutically acceptable carrier and/or a known therapeutic agent.
number: 16
text: The pharmaceutical composition of claim 15, wherein the bispecific binding protein is encoded in a viral vector, preferably wherein the viral vector is an oncolytic virus and intended for in vivo expression in a subject.
number: 17
text: The pharmaceutical composition of claims 15-16 for use in the treatment of cancer, preferably wherein the cancer is a solid tumour, or for use in the treatment of infectious disease.
Office action: search_report, dated 2020-11-04
Rejection reasons: novelty_epc_54
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severity: novelty_destroying
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ref_type: npl
severity: novelty_destroying
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ref_type: npl
severity: background
ref_id: - CATHERINE CARUSO, "ZW25 Effective in HER2-Positive Cancers", CANCER DISCOVERY, US, (20181130), vol. 9, no. 1, doi:10.1158/2159-8290.CD-NB2018-162, ISSN 2159-8274, pages 8.1 - 8, XP055640700 [A] 1-17 * the whole document *
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severity: background
ref_id: - FRANK COMER ET AL, Bispecific and Biparatopic Antibody Drug Conjugates, DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES, SPRINGER INTERNATIONAL PUBLISHING, CHAM, PAGE(S) 267 - 280, (20180101), pages 267 - 280, ISSN 2196-9906, ISBN 978-3-319-21167-1, XP009517114 [A] 1-17 * page  269, paragraph  2 * * page  271, paragraph  1 * * figure 2 *
ref_type: npl
severity: background
Final disposition: pending (2020-11-04)