Therapeutic antibodies and their uses
AssigneePfizer Inc.
InventorsJAMES REASONER APGAR, ANDREA THERESE HOOPER, MALGORZATA AGNIESZKA NOCULA-LUGOWSKA, LEI WU
Life of this patent
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Abstract
The present invention relates to antibodies that specifically bind to B7-H4 (B7 Homology 4, encoded by gene VTCN1) and bispecific antibodies that specifically bind to both B7-H4 and CD3 (Cluster of Differentiation 3), and polynucleotides, pharmaceutical compositions and methods and uses thereof.
Claims36
An isolated antibody that specifically binds to B7-H4, comprising
- (a) a heavy chain variable region (VH) complementarity determining region (CDR) one (CDR1), a VH CDR2 and a VH CDR3 of a VH having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 23, SEQ ID NO:155, SEQ ID NO:
- 156, SEQ ID NO:
- 157, SEQ ID NO:
- 159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:169, SEQ ID NO:
- 171, SEQ ID NO:
- 172, SEQ ID NO:
- 173, SEQ ID NO:
- 174, SEQ ID NO:
- 175 and SEQ ID NO:
- 176;
- and
- (b) a light chain variable region (VL) complementarity determining region one (CDR1), a VL CDR2 and a VL CDR3 of a VL having an amino acid sequence selected from the group consisting of SEQ ID NO:27, SEQ ID NO:
- 139, SEQ ID NO:141, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169 and SEQ ID NO:170.
An isolated antibody that specifically binds to B7-H4, comprising a heavy chain comprising the amino acid sequence of the full-length polypeptide encoded by the open reading frame (ORF) of the polynucleotide deposited under ATCC Accession No. PTA-126779, and a light chain comprising the amino acid sequence of the full-length polypeptide encoded by the open reading frame (ORF) of the polynucleotide deposited under with ATCC Accession No. PTA-126781.
An isolated first antibody that specifically binds to B7-H4, that competes for binding with B7-H4 with a second antibody comprising
- (a) a VH having the amino acid sequence of SEQ ID NO:8, and a VL having the amino acid sequence of SEQ ID NO:13;
- (b) a VH having the amino acid sequence of SEQ ID NO:8, and a VL having the amino acid sequence of SEQ ID NO:13;
- (c) a VH having the amino acid sequence of SEQ ID NO:39, and a VL having the amino acid sequence of SEQ ID NO:43;
- (d) a VH having the amino acid sequence of SEQ ID NO:46, and a VL having the amino acid sequence of SEQ ID NO:49;
- (e) a VH having the amino acid sequence of SEQ ID NO:52, and a VL having the amino acid sequence of SEQ ID NO:54;
- (f) a VH having the amino acid sequence of SEQ ID NO:57, and a VL having the amino acid sequence of SEQ ID NO:60;
- (g) a VH having the amino acid sequence of SEQ ID NO:16, and a VL having the amino acid sequence of SEQ ID NO:19;
- (h) a VH having the amino acid sequence of SEQ ID NO:64, and a VL having the amino acid sequence of SEQ ID NO:67;
- (i) a VH having the amino acid sequence of SEQ ID NO:69, and a VL having the amino acid sequence of SEQ ID NO:70;
- (j) a VH having the amino acid sequence of SEQ ID NO:74, and a VL having the amino acid sequence of SEQ ID NO:77;
- (k) a VH having the amino acid sequence of SEQ ID NO:80, and a VL having the amino acid sequence of SEQ ID NO:84;
- (l) a VH having the amino acid sequence of SEQ ID NO:87, and a VL having the amino acid sequence of SEQ ID NO:90;
- (m) a VH having the amino acid sequence of SEQ ID NO:23, and a VL having the amino acid sequence of SEQ ID NO:27;
- (n) a VH having the amino acid sequence of SEQ ID NO:94, and a VL having the amino acid sequence of SEQ ID NO:96;
- (o) a VH having the amino acid sequence of SEQ ID NO:100, and a VL having the amino acid sequence of SEQ ID NO:77;
- or
- (p) a VH having the amino acid sequence of SEQ ID NO:104, and a VL having the amino acid sequence of SEQ ID NO:67;
- wherein the first antibody has a KD to human B7-H4 of between about 1 micromolar and 0.1 nanomolar.
An isolated antibody that specifically binds to B7-H4, wherein the antibody binds to an epitope on human B7-H4 comprising at least two amino acid residues selected from the group consisting of L44, K45, E46, G47, V48, L49, G50, L51, E64, D66, M68, T99 and K101 of the B7-H4 extracellular domain having the amino acid sequence of SEQ ID NO:
- 1.
An isolated polynucleotide encoding:
- (i) a heavy chain of the antibody of any one of claims 1 to 16;
- or (ii) a light chain of the antibody of claim 1.
A bispecific antibody that specifically binds to both B7-H4 and CD3, comprising a first heavy chain and a first light chain, and a second heavy chain and a second light chain, wherein the first heavy chain and the first light chain form a first arm which comprises a first antigen binding domain that binds to B7-H4, and the second heavy chain and the second light chain form a second arm which comprises a second antigen binding domain that binds to CD3, wherein
- (a) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 20;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:21, a VH CDR3 having the amino acid sequence of SEQ ID NO:160, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 166, a VL CDR2 having the amino acid sequence of SEQ ID NO:25 and a VL CDR3 having the amino acid sequence of SEQ ID NO:153;
- (b) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 205;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:21, a VH CDR3 having the amino acid sequence of SEQ ID NO:160, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 166, a VL CDR2 having the amino acid sequence of SEQ ID NO:25 and a VL CDR3 having the amino acid sequence of SEQ ID NO:153;
- (c) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 206;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:207, a VH CDR3 having the amino acid sequence of SEQ ID NO:160, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 166, a VL CDR2 having the amino acid sequence of SEQ ID NO:25 and a VL CDR3 having the amino acid sequence of SEQ ID NO:153;
- (d) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 5;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:6, a VH CDR3 having the amino acid sequence of SEQ ID NO:7, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 9, a VL CDR2 having the amino acid sequence of SEQ ID NO:10 and a VL CDR3 having the amino acid sequence of SEQ ID NO:138;
- (e) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 200;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:201, a VH CDR3 having the amino acid sequence of SEQ ID NO:7, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 9, a VL CDR2 having the amino acid sequence of SEQ ID NO:10 and a VL CDR3 having the amino acid sequence of SEQ ID NO:138;
- (f) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 199;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:6, a VH CDR3 having the amino acid sequence of SEQ ID NO:7, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 9, a VL CDR2 having the amino acid sequence of SEQ ID NO:10 and a VL CDR3 having the amino acid sequence of SEQ ID NO:138;
- (g) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 20;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:21, a VH CDR3 having the amino acid sequence of SEQ ID NO:160, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 152, a VL CDR2 having the amino acid sequence of SEQ ID NO:41 and a VL CDR3 having the amino acid sequence of SEQ ID NO:153;
- (h) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 5;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:6, a VH CDR3 having the amino acid sequence of SEQ ID NO:7, a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 9, and the first light chain comprises a VL CDR2 having the amino acid sequence of SEQ ID NO:10 and a VL CDR3 having the amino acid sequence of SEQ ID NO:138;
- or
- (i) the first heavy chain comprises a VH CDR1 having the amino acid sequence of SEQ ID NO:
- 5;
- a VH CDR2 having the amino acid sequence of SEQ ID NO:130, a VH CDR3 having the amino acid sequence of SEQ ID NO:7, and the first light chain comprises a VL CDR1 having the amino acid sequence of SEQ ID NO:
- 9, a VL CDR2 having the amino acid sequence of SEQ ID NO:10 and a VL CDR3 having the amino acid sequence of SEQ ID NO:138.
A bispecific antibody that specifically binds to both B7-H4 and CD3, comprising a first heavy chain and a first light chain, and a second heavy chain and a second light chain, wherein the first heavy chain and the first light chain form a first antibody arm which comprises a first antigen binding domain that binds to B7-H4, and the second heavy chain and the second light chain form a second antigen binding domain that binds to CD3, wherein
- (a) the first heavy chain having the amino acid sequence of SEQ ID NO:
- 190;
- and the first light chain having the amino acid sequence of SEQ ID NO:
- 191;
- and
- (b) the second heavy chain having the amino acid sequence of SEQ ID NO:188, and the second light chain having the amino acid sequence of SEQ ID NO:
- 189.
A bispecific antibody that specifically binds to both B7-H4 and CD3, comprising a first heavy chain and a first light chain, and a second heavy chain and a second light chain, wherein the first heavy chain and the first light chain form a first antibody arm which comprises a first antigen binding domain that binds to B7-H4, and the second heavy chain and the second light chain forms a second antigen binding domain that binds to CD3, wherein
- (a) the first heavy chain having the amino acid sequence of SEQ ID NO:
- 186;
- and the first light chain having the amino acid sequence of SEQ ID NO:
- 187;
- and
- (b) the second heavy chain having the amino acid sequence of SEQ ID NO:188, and the second light chain having the amino acid sequence of SEQ ID NO:189.
A bispecific antibody that specifically binds to B7-H4 and CD3, comprising a first heavy chain and a first light chain, and a second heavy chain and a second light chain, wherein the first heavy chain and the first light chain form a first antibody arm which comprises a first antigen binding domain that binds to B7-H4, and the second heavy chain and the second light chain form a second antigen binding domain that binds to CD3, wherein
- (a) the first heavy chain comprises the amino acid sequence of the full-length polypeptide encoded by the open reading frame (ORF) deposited under ATCC Accession No. PTA-126779, and the first light chain comprises the amino acid sequence of the full-length polypeptide encoded by the open reading frame (ORF) deposited under ATCC Accession No. PTA-126781;
- and
- (b) the second heavy chain comprises the amino acid sequence of the full-length polypeptide encoded by the open reading frame (ORF) deposited under ATCC Accession No. PTA-126780, and the second light chain comprises the amino acid sequence of the full-length polypeptide encoded by the open reading frame (ORF) deposited under ATCC Accession No. PTA-126782.
A bispecific antibody that specifically binds to both B7-H4 and CD3, wherein the antibody binds to an epitope on human B7-H4 comprising at least two amino acid residue from the group consisting of L44, K45, E46, G47, V48, L49, G50, L51, S63, E64, D66, M68, T99 and K101 of the B7-H4 amino acid sequence of SEQ ID NO:
- 1.
The method of claim 43, wherein the condition is a cancer.
Dependencies are inferred from the claim text.