NOVEL ANTIBODY SEQUENCES FOR DIAGNOSTICS AND THERAPEUTICS
Aspects of the present disclosure relate generally to novel antigen binding sequences and uses thereof. More specifically, certain features of the present disclosure concern antibodies, minibodies, and cys-diabodies for use in targeting the protein FAP. The antigen binding sequences herein may be used as part of treatment to confer health benefits to subjects in need thereof. The antigen binding sequences can also be used for detection, targeting, and imaging purposes.
1 - 54 . (canceled)
55 . An isolated antigen binding construct comprising:
a HCDR1 comprising the amino acid sequence of SEQ ID NO: 81 (NYDIN), or a sequence that has no more than 3 point mutations thereto;
a HCDR2 comprising the amino acid sequence of SEQ ID NO: 82 (LIWTGGGTN), or a sequence that has no more than 3 point mutations thereto; and/or
a HCDR3 comprising the amino acid sequence of SEQ ID NO: 83 (GGPLVWYALDY), or a sequence that has no more than 3 point mutations thereto.
56 . The isolated antigen binding construct of claim 55 , further comprising:
a LCDR1 comprising the amino acid sequence of SEQ ID NO: 84 (KASQDVSTAVA), or a sequence that has no more than 3 point mutations thereto;
a LCDR2 comprising the amino acid sequence of SEQ ID NO: 85 (SASYRYT), or a sequence that has no more than 3 point mutations thereto; and/or
a LCDR3 comprising the amino acid sequence of SEQ ID NO: 86 (QQHYSNPRT), or a sequence that has no more than 3 point mutations thereto.
57 . The isolated antigen binding construct of claim 55 , wherein there are no more than 2 point mutations in HCDR1, HCDR2 and/or HCDR3.
58 . The isolated antigen binding construct of claim 55 , further comprising a variable heavy domain (VH) having the amino acid sequence of SEQ ID NO: 87.
59 . The isolated antigen binding construct of claim 56 , further comprising a variable light domain (VL) having the amino acid sequence of SEQ ID NO: 88.
60 . The isolated antigen binding construct of claim 55 , wherein the antigen binding construct is specific against FAP alpha.
61 . The isolated antigen binding construct of claim 55 , wherein the antigen binding construct does not bind DPP4.
62 . The isolated antigen binding construct of claim 55 , further comprising a payload.
63 . The isolated antigen binding construct of claim 62 , wherein the payload is selected from among a moiety that is fluorescent, luminescent, colorimetric, radioactive, non-radioactive, a chemotherapeutic agent, a chemically reactive agent and a detectable marker.
64 . A composition comprising the isolated antigen binding construct of claim 55 , further comprising at least one payload selected from a group consisting of 18 F, 18 F-FAC, 32 P, 33 P, 45 Ti, 47 Sc, 52 Fe, 59 Fe, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 75 Sc, 77 As, 86 Y, 90 Y, 89 Sr, 89 Zr, 94 Tc, 94 Tc, 99 mTc, 99 Mo, 105 Pd, 105 Rh, 111 Ag, 111 In, 123 I, 124 I, 125 I, 131 I, 142 Pr, 143 Pr, 149 Pm, 149 Tb, 153 Sm, 154-158 Gd, 161 Tb, 166 Dy, 166 Ho, 169 Er, 175 Lu, 177 Lu, 186 Re, 188 Re, 189 Re, 194 Ir, 198 Au, 199 Au, 211 At, 211 Pb, 212 Bi, 212 Pb, 213 Bi, 223 Ra, 227 Th and 225 Ac, or any combination thereof.
65 . A composition comprising the isolated antigen binding construct of claim 55 and at least one chelator.
66 . A pharmaceutical composition comprising an amount of the isolated antigen binding construct of claim 55 that is effective for treating a subject with cancer and/or a tumor; and a pharmaceutically acceptable carrier.
67 . A method of treating, inhibiting, or ameliorating a disease in a subject, comprising: administering a pharmaceutical composition comprising the isolated antigen binding construct of claim 55 to the subject in need thereof.
68 . A method of targeting FAP protein on a fibroblast in a subject, comprising: administering a pharmaceutical composition comprising the isolated antigen binding construct of claim 55 to the subject.
69 . A method of inhibiting, ameliorating, damaging, or inducing apoptosis in a cancer or tumor associated macrophage in a subject, comprising: administering a pharmaceutical composition comprising the isolated antigen binding construct of claim 55 to the subject in need thereof.
70 . A method of identifying a disease in a subject, comprising:
administering a pharmaceutical composition comprising the isolated antigen binding construct of claim 55 to the subject;
screening for the binding of the isolated antigen binding construct to FAP; and
determining whether the subject has a disease thereof based upon the presence or absence of binding to FAP.
71 . An isolated antigen binding construct, comprising:
a HCDR1 comprising amino acids having at least 80% identity with the amino acid sequence of SEQ ID NO: 1 (EYTIH);
a HCDR2 comprising amino acids having at least 80% identity with the amino acid sequence of SEQ ID NO: 2 (GINPNNGIPNYNQKFKG);
a HCDR3 comprising amino acids having at least 80% identity with the amino acid sequence of SEQ ID NO: 3 (RRIAYGYDEGHAMDY);
a LCDR1 comprising amino acids having at least 80% identity with the amino acid sequence of SEQ ID NO: 4 (KSSQSLLYSRNQKNYLA);
a LCDR2 comprising amino acids having at least 80% identity with the amino acid sequence of SEQ ID NO: 5 (WASTRES); and
a LCDR3 comprising amino acids having the amino acid sequence of SEQ ID NO: 6 (QQYYSYPLT).
72 . The antigen binding construct of claim 71 , comprising:
a variable heavy domain (VH) of SEQ ID NO: 7; and
a variable light domain (VL) of SEQ ID NO: 8 or 9.
73 . The isolated antigen binding construct of claim 72 , comprising at least one VH framework residue selected from the group consisting of:
an Alanine at position 24 of the sequence in SEQ ID NO: 7; or
a Glycine at position 26 of the sequence in SEQ ID NO: 7 and
at least one VL framework residue selected from the group consisting of:
a Serine at position 73 of the sequence in SEQ ID NO: 8;
an Arginine at position 83 of the sequence in SEQ ID NO: 8;
a Glutamic acid at position 85 of the sequence in SEQ ID NO:8;
a Proline at position 86 of the sequence in SEQ ID NO: 8;
a Phenylalanine at position 89 of the sequence in SEQ ID NO: 8; or
a Tyrosine at position 98 of the sequence in SEQ ID NO: 8.
74 . An isolated antigen binding construct comprising amino acids having 100% identity with an amino acid sequence selected from the any one of the sequences listed in SEQ ID NOS: 23-44, 12-43, 12-45, 87-96, 110-115, 122-125, or 140-143.