# US 2020/0399394 A1 · Antibodies That Bind CD39 and Uses Thereof

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- Number: US 2020/0399394 A1
- Document ID: US20200399394A1
- Status: Published application
- Kind: A1
- Application number: 17/015,864
- Filed: 2020-09-09
- Published: 2020-12-24
- Earliest claimed: 2018-03-14
- Assignees: Surface Oncology, Inc.
- Applicants: Surface Oncology, Inc.
- Inventors: Scott CHAPPEL; Andrew LAKE; Michael WARREN; Austin DULAK; Erik DEVEREAUX; Pamela M. HOLLAND; Tauqeer ZAIDI; Matthew RAUSCH; Bianka Prinz; Nels P. NIELSON; Sonia DAS
- Web page: https://patentgrep.com/patent/US20200399394A1

## CPC

- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- C12N 15/85: for animal cells
- G01N 33/573: for enzymes or isoenzymes
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 2039/505: {comprising antibodies}
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/916: acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure relates to anti-CD39 antibodies, and antigen binding portions thereof and their use in treating cancer.

## Claims

### Claim 1

An isolated anti-CD39 antibody, or an antigen binding portion thereof, wherein the antibody or antigen binding portion thereof exhibits one or more of the following properties:
a. binds to recombinant human CD39 and/or to membrane-bound human CD39;
b. binds to human CD39 with an equilibrium dissociation constant (KD) of less than 10 nM;
c. inhibits or reduces an enzymatic activity of human CD39;
d. inhibits or reduces conversion by human CD39 of extracellular adenosine triphosphate (eATP) or extracellular adenosine diphosphate (eADP) to extracellular adenosine monophosphate (eAMP);
e. increases or enhances a level of eATP;
f. decreases or reduces extracellular adenosine;
g. maintains, increases or enhances an immunostimulatory level of eATP;
h. increases or enhances proliferation of a lymphocyte;
i. increases or enhances expression of one or more dendritic cell activation markers;
j. increases or enhances secretion of one or more cytokines from dendritic cells;
k. increases or enhances macrophage infiltration in tumors;
l. increases or enhances secretion of macrophage attracting chemokines;
m. antagonizes human CD39 in a tumor microenvironment of a tissue;
n. cross-reacts with cynomolgus CD39; and
o. a combination of any one of (a)-(n).

### Claim 2 (depends on 1)

The isolated anti-CD39 antibody, or antigen binding portion thereof, of claim 1, wherein the antibody or antigen binding portion thereof comprises, consists, or consists essentially of:
i) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 1, 2 and 3, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 11, 12, and 13, respectively; or
ii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 4, 5, and 6, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 15, 16, and 17, respectively; or
iii) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7; or
iv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
v) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 21, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
vi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 23, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
vii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 25, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
viii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 27, 28, and 29, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 37, 38, and 39, respectively; or
ix) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 30, 31, and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 40, 41, and 42, respectively; or
x) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 33, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 43; or
xi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 35, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 47, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xiii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 49, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xiv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 51, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xv) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 53, 54, and 55, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 63, 64, and 65, respectively; or
xvi) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 56, 57, and 58, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 66, 67, and 68, respectively; or
xvii) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 69; or
xviii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 61, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xix) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 73, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xx) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 75, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xxi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 77, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xxii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 79, 80, and 81, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 89, 90, and 91, respectively; or
xxiii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 82, 83, and 84, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 92, 93, and 94, respectively; or
xxiv) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 85, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 95; or
xxv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 87, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxvi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 99, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxvii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 101, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxviii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 103, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxix) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 105, 106, and 107, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 115, 116, and 117, respectively; or
xxx) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 108, 109, 110, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 118, 119, and 120, respectively; or
xxxi) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 111, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 121; or
xxxii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 113, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123; or
xxxiii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 125, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123; or
xxxiv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 127, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123; or
xxxv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 129, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123.

### Claim 3

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody or antigen binding portion thereof increases proliferation of a lymphocyte, optionally wherein the lymphocyte is a tumor-infiltrating lymphocyte, or CD4+ T cell.

### Claim 4

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody or antigen binding portion thereof enhances expression of one or more dendritic cell activation markers, optionally wherein the dendritic cell activation marker is CD86, HLA-DR, or a both CD86 and HLA-DR.

### Claim 5

The isolated anti-CD39 antibody, or antigen binding portion thereof of any one of the preceding claims, wherein the antibody or antigen binding portion thereof enhances secretion of one or more cytokines from dendritic cells, optionally wherein the cytokine is IL-16, IL-12/IL-23p40, VEGFA, or any combination thereof.

### Claim 6

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antagonism of human CD39 occurs in a tumor microenvironment, optionally wherein the antagonism is non-competitive and/or allosteric.

### Claim 7

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody or antigen binding portion thereof cross-reacts with cynomolgus CD39.

### Claim 8

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody is an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgD, or an IgE antibody.

### Claim 9

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody is a wild type or mutant IgG1 or IgG4 antibody.

### Claim 10

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, comprising a mutant IgG4 heavy chain constant region, wherein the mutation i) reduces the ability of the IgG4 to form half-molecules; and/or ii) minimizes binding to Fc receptors.

### Claim 11

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, comprising a mutant IgG4 heavy chain constant region comprising an S228P mutation.

### Claim 12

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, comprising a mutant IgG4 heavy chain constant region comprising S228P and L235E mutations.

### Claim 13

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody or antigen binding portion thereof comprises the heavy chain CDR3 sequence set forth in SEQ ID NO: 3.

### Claim 14

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody or antigen binding portion thereof binds to substantially the same epitope as a reference antibody or antigen binding portion thereof comprising the heavy chain CDR3 sequence set forth in SEQ ID NO: 3.

### Claim 15

The isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims, wherein the antibody or antigen binding portion thereof binds to substantially the same epitope as a reference antibody or antigen binding portion thereof comprising:
i) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 1, 2 and 3, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 11, 12, and 13, respectively; or
ii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 4, 5, and 6, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 15, 16, and 17, respectively; or
iii) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7; or
iv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
v) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 21, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
vi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 23, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
vii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 25, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; or
viii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 27, 28, and 29, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 37, 38, and 39, respectively; or
ix) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 30, 31, and 32, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 40, 41, and 42, respectively; or
x) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 33, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 43; or
xi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 35, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 47, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xiii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 49, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xiv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 51, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 45; or
xv) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 53, 54, and 55, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 63, 64, and 65, respectively; or
xvi) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 56, 57, and 58, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 66, 67, and 68, respectively; or
xvii) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 69; or
xviii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 61, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xix) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 73, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xx) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 75, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xxi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 77, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 71; or
xxii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 79, 80, and 81, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 89, 90, and 91, respectively; or
xxiii) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 82, 83, and 84, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 92, 93, and 94, respectively; or
xxiv) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 85, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 95; or
xxv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 87, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxvi) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 99, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxvii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 101, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxviii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 103, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 97; or
xxix) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 105, 106, and 107, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 115, 116, and 117, respectively; or
xxx) heavy chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 108, 109, 110, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising SEQ ID NOs: 118, 119, and 120, respectively; or
xxxi) a variable heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 111, and a variable light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 121; or
xxxii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 113, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123; or
xxxiii) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 125, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123; or
xxxiv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 127, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123; or
xxxv) a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 129, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 123.

### Claim 16

A nucleic acid encoding the anti-CD39 antibody, or antigen binding portion thereof, of any one of the preceding claims.

### Claim 17 (depends on 16)

An expression vector comprising the nucleic acid of claim 16.

### Claim 18 (depends on 17)

A cell transformed with an expression vector of claim 17.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A pharmaceutical composition comprising an isolated anti-CD39 antibody or antigen binding portion thereof, of any one of claims 1-15, or the nucleic acid of claim 16, and a pharmaceutically acceptable carrier.

### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 19)

A method of treating a cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of the isolated anti-CD39 antibody, or antigen binding portion thereof, of any one claims 1-15 or the pharmaceutical composition of claim 19.

### Claim 21 (depends on 21)

The method of claim 21, wherein the cancer is selected from the group consisting of: lung cancer (e.g., non-small cell lung cancer), ovarian cancer, kidney cancer, testicular cancer, pancreas cancer, breast cancer (e.g., triple-negative breast cancer), melanoma, head and neck cancer (e.g., squamous head and neck cancer), colorectal cancer, bladder cancer, endometrial cancer, prostate cancer, thyroid cancer, hepatocellular carcinoma, gastric cancer, brain cancer, lymphoma an renal cancer (e.g., renal cell carcinoma).

### Claim 22 (depends on 20, 21)

The method of any one of claims 20-21, wherein the isolated anti-CD39 antibody, or antigen binding portion thereof, is administered in combination with one or more additional therapeutic agents or procedure, wherein the additional therapeutic agent or procedure is selected from the group consisting of: a chemotherapy, a targeted anti-cancer therapy, an oncolytic drug, a cytotoxic agent, an immune-based therapy, a cytokine, surgical procedure, a radiation procedure, an activator of a costimulatory molecule, an inhibitor of an inhibitory molecule, a vaccine, or a cellular immunotherapy, or a combination thereof.

### Claim 23 (depends on 22)

The method of claim 22, wherein the one or more additional therapeutic agents is a PD-1 antagonist, an adenosine A2AR antagonist, a CD73 inhibitor, a CTLA-4 inhibitor, a TIM-3 inhibitor, a LAG-3 inhibitor, chimeric antigen receptor (CAR) cell therapy, an anthracycline, or a combination thereof.

### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 19)

A method of detecting human CD39 in vivo or ex vivo in a biological sample comprising (i) contacting the sample (and optionally, a reference/control sample or subject) with the antibody of any one of claims 1-15, or the pharmaceutical composition of claim 19, under conditions that allow interaction of the antibody molecule and human CD39 to occur, and (ii) detecting formation of a complex between the antibody molecule and the sample or the subject (and optionally, the reference sample or subject).

### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 19)

A kit comprising the isolated anti-CD39 antibody, or antigen binding portion thereof, of any one of claims 1-15, the nucleic acid of claim 16, or the pharmaceutical composition of claim 19 and instructions for use in treating cancer in a subject, optionally with instructions for use in combination with one or more additional therapeutic agents or procedure.