Antibodies to mucin-16 (MUC16), encoding polynucleotides and methods of treating MUC16-positive cancer

1. An anti-mucin 16 (MUC16) construct comprising an antibody moiety that immunospecifically recognizes a mucin 16 (MUC16) polypeptide, wherein the antibody moiety comprises:

(a) (i) a variable heavy (VH) chain comprising a heavy chain complementarity determining region (HC-CDR) 1, a HC-CDR2, and a HC-CDR3 of the heavy chain variable domain of SEQ ID NO: 2; and

(ii) a variable light (VL) chain comprising a light chain complementarity determining region (LC-CDR) 1, a LC-CDR2, and a LC-CDR3 of the light chain variable domain of SEQ ID NO: 3;

or

(b) (i) a variable heavy (VH) chain comprising a heavy chain complementarity determining region (HC-CDR) 1, a HC-CDR2, and a HC-CDR3 of the heavy chain variable domain of SEQ ID NO: 10; and

(ii) a variable light (VL) chain comprising a light chain complementarity determining region (LC-CDR) 1, a LC-CDR2, and a LC-CDR3 of the light chain variable domain of SEQ ID NO: 11, optionally wherein the antibody moiety

immunospecifically binds to the ectodomain of MUC16; or

comprises human-derived heavy and light chain constant regions; or

is an immunoglobulin comprising two identical heavy chains and two identical light chains, optionally wherein the immunoglobulin is an IgG, or

is a full-length antibody, a monoclonal antibody, a Fab, a Fab′, a F(ab′)2, an Fv, or a single chain Fv (scFv).

2. The anti-MUC16 construct of claim 1 , wherein the antibody moiety comprises:

(a) (i) a variable heavy (VH) chain comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising the amino acid sequence of SEQ ID NO: 4; a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and

(ii) a variable light (VL) chain comprising: a light chain complementarity determining region (LC-CDR) 1 comprising the amino acid sequence of SEQ ID NO: 7; a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 9;

or

(b) (i) a variable heavy (VH) chain comprising a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 12; a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13; and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 14; and

(ii) a variable light (VL) chain comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 15; a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 17.

3. The anti-MUC16 construct of claim 1 , wherein the VH chain is a human VH chain and/or the VL chain is a human VL chain.

4. The anti-MUC16 construct of claim 1 , wherein the antibody moiety comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 2 and/or a VL comprising the amino acid sequence of SEQ ID NO: 3; or (b) a VH comprising the amino acid sequence of SEQ ID NO: 10 and/or a VL comprising the amino acid sequence of SEQ ID NO: 11.

5. The anti-MUC16 construct of claim 1 , wherein the anti-MUC16 construct is monospecific, bispecific or multispecific.

6. The anti-MUC16 construct of claim 1 , wherein the anti-MUC16 construct is a tandem scFv, a diabody (Db), a single chain diabody (scDb), a dual-affinity retargeting (DART) antibody, a F(ab′)2, a dual variable domain (DVD) antibody, a knob-into-hole (KiH) antibody, a dock and lock (DNL) antibody, a chemically cross-linked antibody, a heteromultimeric antibody, a chimeric antigen receptor (CAR) or a heteroconjugate antibody.

7. The anti-MUC16 construct of claim 5 , wherein the antibody moiety that immunospecifically recognizes MUC16 is a first antibody moiety, and wherein the anti-MUC16 construct further comprises a second antibody moiety that immunospecifically recognizes a second antigen, optionally wherein the second antigen is a CD3 antigen.

8. The anti-MUC16 construct of claim 1 further conjugated to a peptide agent, a detection agent, an imaging agent, a therapeutic agent, or a cytotoxic agent.

9. A polypeptide of the anti-MUC16 construct of claim 1 having an amino acid sequence of one or more of SEQ ID NOs: 2-17.

10. A polynucleotide or cell comprising a nucleic acid having a sequence encoding the polypeptide of claim 9 .

11. A vector or cell comprising the polynucleotide of claim 10 operably linked to a promoter.

12. An isolated cell comprising the vector of claim 11 .

13. A pharmaceutical composition comprising: a therapeutically effective amount of the anti-MUC16 construct of claim 1 , or a polypeptide, a polynucleotide, or vector comprising the anti-MUC16 construct; and a pharmaceutically acceptable carrier.

14. A method of treating a MUC16-positive cancer in a patient in need thereof, comprising administering to said patient the pharmaceutical composition of claim 13 .

15. The method of claim 14 , wherein the MUC16-positive cancer is a cancer of the ovary, lung, pancreas, breast, uterine, fallopian tube, or primary peritoneum.