Cancer associated antibody compositions and methods of use
AssigneeTotient, Inc.
InventorsDaniele BIASCI, Ines de Santiago Domingos de JESUS, Berke Cagkan TOPTAS
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Abstract
The disclosure herein relates to novel cancer-associated antibodies that are used in the treatment and diagnosis of a cancer. The complete polypeptide and nucleic acid consensus sequences of the antibodies disclosed herein are reconstructed in silico.
Claims148
An antibody or antigen-binding fragment thereof comprising at least one of:
- a complementarity-determining region heavy chain 1 (CDR-H1), a CDR-H2 and a CDR-H3, wherein the CDR-H1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 85-98, the CDR-H2 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 57-70, and the CDR-H3 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 29-42.
An antibody or antigen-binding fragment thereof that comprising at least one of:
- a complementarity-determining region light chain 1 (CDR-L1), a CDR-L2 and a CDR-L3, wherein the CDR-L1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 99-112, the CDR-L2 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 71-84, and the CDR-L3 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 43-56.
An antibody or antigen-binding fragment thereof comprising:
- a complementarity-determining region heavy chain 1 (CDR-H1), a CDR-H2 and a CDR-H3, wherein the CDR-H1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 85-98, the CDR-H2 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 57-70, and the CDR-H3 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 29-42;
- and
- a complementarity-determining region light chain 1 (CDR-L1), a CDR-L2 and a CDR-L3, wherein the CDR-L1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 99-112, the CDR-L2 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 71-84, and the CDR-L3 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS:
- 43-56.
The antibody or antigen-binding fragment thereof, wherein the cutaneous melanoma is superficial spreading melanoma, nodular melanoma, acral lentiginous melanoma, subungual melanoma, lentigo maligna melanoma, desmoplastic melanoma, mucosal melanoma, or polypoid melanoma.
An antibody or antigen-binding fragment thereof comprising:
- (a) a variable heavy chain, wherein the variable heavy chain comprises a reconstructed polypeptide consensus sequence having at least 95% identity to an amino acid sequence selected from any one of SEQ ID NOS:
- 1-14;
- (b) a variable light chain, wherein the variable light chain comprises a reconstructed polypeptide consensus sequence having at least 95% sequence identity to an amino acid sequence selected from any one of SEQ ID NOS:
- 15-28;
- or
- (c) the variable heavy chain as in (a) and the variable light chain as in (b).
An isolated nucleic acid molecule comprising at least one of;
- (a) a nucleic acid sequence encoding a CDR-H1, wherein the nucleic acid sequence is selected from SEQ ID NOS:
- 197-210;
- (b) a nucleic acid sequence encoding a CDR-H2, wherein the nucleic acid sequence is selected from SEQ ID NOS:
- 169-182;
- (c) a nucleic acid sequence encoding a CDR-H3, wherein the nucleic acid sequence is selected from SEQ ID NOS:
- 141-154;
- (d) a nucleic acid sequence encoding a CDR-L1, wherein the nucleic acid sequence is selected from SEQ ID NOS:
- 211-224;
- (e) a nucleic acid sequence encoding a CDR-L2, wherein the nucleic acid sequence is selected from SEQ ID NOS:
- 183-196;
- and
- (f) a nucleic acid sequence encoding a CDR-L3, wherein the nucleic acid sequence is selected from SEQ ID NOS:
- 155-168.
An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a heavy chain polypeptide of an antibody, wherein the nucleic acid sequence is selected from any one of SEQ ID NOS:
- 113-126.
An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a light chain polypeptide of an antibody, wherein the nucleic acid sequence is selected from any one of SEQ ID NOS:
- 127-140.
The kit further comprising a therapeutically effective amount of a second therapeutic agent.
An antibody or an antigen binding fragment thereof that binds to a Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1) protein or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO 85, CDR-H2 of SEQ ID NO:
- 57, and CDR-H3 of SEQ ID NO:
- 29;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO 99, CDR-L2 of SEQ ID NO:
- 71, and CDR-L3 of SEQ ID NO:
- 43;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody or an antigen binding fragment thereof that binds to a Chromobox protein (CBX) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 87, CDR-H2 of SEQ ID NO:
- 59, and CDR-H3 of SEQ ID NO:
- 31;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 101, CDR-L2 of SEQ ID NO:
- 73, and CDR-L3 of SEQ ID NO:
- 45;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody that competes with an antibody or antigen binding fragment of any one of claims 75-82 for binding to CBX protein, wherein the antibody binds to human CBX and mouse CBX.
An antibody or an antigen binding fragment thereof that selectively binds to a Cancer/Testis Antigen 1B (CTAG1A) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 89, CDR-H2 of SEQ ID NO:
- 61, and CDR-H3 of SEQ ID NO:
- 33;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 103, CDR-L2 of SEQ ID NO:
- 75, and CDR-L3 of SEQ ID NO:
- 47;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody or an antigen binding fragment thereof that selectively binds to an Alpha and Gamma Adaptin Binding Protein (AAGAB) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 90, CDR-H2 of SEQ ID NO:
- 62, and CDR-H3 of SEQ ID NO:
- 34;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 104, CDR-L2 of SEQ ID NO:
- 76, and CDR-L3 of SEQ ID NO:
- 48;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody or an antigen binding fragment thereof that selectively binds to Kinesin light chain 4 protein (KLC4) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 91, CDR-H2 of SEQ ID NO:
- 63, and CDR-H3 of SEQ ID NO:
- 35;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 105, CDR-L2 of SEQ ID NO:
- 77, and CDR-L3 of SEQ ID NO:
- 49;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody or an antigen binding fragment thereof that selectively binds to Melanoma-associated antigen 3 (MAGE-A3) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 92, CDR-H2 of SEQ ID NO:
- 64, and CDR-H3 of SEQ ID NO:
- 36;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 106, CDR-L2 of SEQ ID NO:
- 78, and CDR-L3 of SEQ ID NO:
- 50;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody or an antigen binding fragment thereof that selectively binds to Inorganic pyrophosphatase (PPA1) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 94, CDR-H2 of SEQ ID NO:
- 66, and CDR-H3 of SEQ ID NO:
- 38;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 108, CDR-L2 of SEQ ID NO:
- 80, and CDR-L3 of SEQ ID NO:
- 52;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody or an antigen binding fragment thereof that selectively binds to interleukin-14A (IL-14A) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 95, CDR-H2 of SEQ ID NO:
- 67, and CDR-H3 of SEQ ID NO:
- 39;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 109, CDR-L2 of SEQ ID NO:
- 81, and CDR-L3 of SEQ ID NO:
- 53;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
An antibody or an antigen binding fragment thereof that selectively binds to O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) or a variant thereof, comprising at least one of
- (a) a variable heavy chain region, wherein the variable heavy chain region comprises a complementarity-determining region heavy chain 1 (CDR-H1) of SEQ ID NO:
- 98, CDR-H2 of SEQ ID NO:
- 70, and CDR-H3 of SEQ ID NO:
- 42;
- (b) a variable light chain region, wherein the variable light chain region comprises a complementarity-determining region light chain 1 (CDR-L1) of SEQ ID NO:
- 112, CDR-L2 of SEQ ID NO:
- 84, and CDR-L3 of SEQ ID NO:
- 56;
- or
- (c) the variable heavy chain of (a) and the variable light chain of (b).
Dependencies are inferred from the claim text.