Amhrii antibody-drug conjugates and uses thereof

Abstract

The present disclosure provides AMHRII antibody-drug conjugates and uses thereof.

Description

Attorney Docket No.14529-134-228 AMHRII ANTIBODY-DRUG CONJUGATES AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 492,975, filed March 29, 2023, the disclosure of which is incorporated by reference herein in its entirety. SEQUENCE LISTING

[0002] This application contains a computer readable Sequence Listing which has been submitted in XML file format with this application, the entire content of which is incorporated by reference herein in its entirety. The Sequence Listing XML file submitted with this application is entitled “14529-134-228_SEQ_LISTING.xml”, was created on March 27, 2024, and is 28,775 bytes in size. FIELD

[0003] The present disclosure relates generally to antibody-drug conjugates (ADCs) that comprise anti-Müllerian hormone type II receptor antibodies and methods of their use. BACKGROUND

[0004] Members of the transforming growth factor-beta (TGF-beta) superfamily are key regulators of various physiological processes. The Anti-Müllerian Hormone (AMH) is a 140 kDa glycoprotein, and a member of the TGF-beta superfamily, which is well known for its role during male sexual differentiation (Jasso, N. et al., Pediatr Endocrinol. Rev.2006; 3(4):347-358).

[0005] In the field of cancer, the implication of AMHRII signaling is more complex. As mentioned above, AMHRII belongs to the TGFβ receptor superfamily. TGFβ induces in general anti-proliferative responses in normal and cancer cells. Indeed, TGFβR2 and SMAD4 inactivating mutations and deletions are seen in various tumors and thought to be one of the triggers of the multistep tumorigenesis at early stages (Vogelstein et al., Science 2013; 339(6127):1545-1558; Levy et al., Molec Cell Biol 2005; 25(18):8108-8125).

[0006] AMH and AMHRII are described as being implicated in the inhibition of cell cycle and as inducing apoptosis in cancers. Accordingly, AMH is known in the field of cancers as being a factor that protects the organism against cancer (M. Gowkielewicz et al.; Int. J. Mol. Sci.2019; 20(6):1325). As such, much of the current research is oriented toward facilitating, increasing, or improving the effect of AMH in cancers, and thus its interaction with its receptor, as this interaction is known as triggering the signaling pathways of interest. 1 NAI-1539665006v1

[0007] AMH and / or AMHRII expression was recently reported in various solid tumors other than gynecological. Indeed, AMH expression was described in many solid tumors, such as gliomas, lung cancers, colorectal cancers, head and neck cancers, stomach cancers, pancreatic cancers, renal cancers, urothelial cancers, prostate cancers, testis cancers, breast cancers and in melanomas (Human Protein Atlas).

[0008] AMHRII was also demonstrated as being expressed at the surface of various human cancer cells, which include especially colon cancer, lung cancer, hepatocellular carcinoma, testis cancer, pancreatic cancer, kidney cancer, breast cancer, thyroid cancer, gastric cancer, adrenal cancer, bladder cancer and prostate cancer. (Barret et al., Proc Amer Soc Clin Oncol, 37, Abst 774, 2018).

[0009] WO 2021 / 0789959 A1, which is incorporated herein by reference in its entirety, describes that inhibiting the interactions of AMH with its receptor AMHRII leads to a reduction of AMHRII expressing cells' viability. However, there is a need in the art for antibody-drug conjugates (ADCs) that can target AMHRII to treat, prevent, or alleviate AMHRII-mediated diseases, disorders, or conditions, including AMHRII-expressing-cancers, such as reproductive cancers like ovarian cancer, serous cancer, hypernephroma, endometrioid, colloidal epithelium, prostate cancer, germ cell cancer, endometrial cancer, mixed Müllerian malignant tumor of the uterus, leiomyosarcoma, and endometrial stromal sarcoma, as well as AMHRII-expressing non-gynecological cancers. 2 NAI-1539665006v1SUMMARY

[0010] In one aspect, the present disclosure provides an antibody-drug conjugate (ADC) ofor a salt thereof, wherein: n is an integer from 1 to 8, and Ab represents an antibody that binds to AMHRII (“AMHRII antibody”).

[0011] In some embodiments, the point of attachment to the Ab is through a cysteine or a lysine residue of the antibody. In further embodiments, the point of attachment to the Ab is from two cysteine residues which form an interchain disulfide bridge in an AMHRII antibody when not conjugated as the ADC of Formula (I) or a salt thereof, for example, between two heavy chains (such as C226 and / or C229 accordingly to EU numbering) or between a heavy chain and a light chain (such as C220 of a heavy chain accordingly to EU numbering and C214 of a light chain according to EU and / or Kabat numbering). Accordingly, n is selected from the group consisting of 2, 4, 6 and 8. In some embodiments, the point of attachment to the Ab is through any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the AMHRII antibody according to the EU numbering. 3 NAI-1539665006v1

[0012] In some embodiments, the ADC is of Formula (I-A) or a salt thereof. .

[0013] In other embodiments, the ADC is of Formula (I-B) or a salt thereof:. (I-B) 4 NAI-1539665006v1

[0014] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (A1):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted sulfurs are from cysteine residues (optionally selected from C220, C226, or C229 of a heavy chain of the AMHRII antibody according to the EU numbering, or C214 of a light chain of the AMHRII antibody according to the EU or Kabat numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof: 5 NAI-1539665006v1wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (A1).

[0015] In some embodiments, X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (A1). 6 NAI-1539665006v1

[0016] In other embodiments, X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (A1). 7 NAI-1539665006v1

[0017] In yet another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (B1):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue (optionally any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the AMHRII antibody according to the EU numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof:, 8 NAI-1539665006v1wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (B1).

[0018] In some embodiments, X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (B1). 9 NAI-1539665006v1

[0019] In other embodiments, X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (B1).

[0020] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, (A1), or (B1) comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14. In one embodiment, the AMHRII-ADC of Formula (B1) comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering), such as ADC-033 as disclosed herein. In one embodiment, the AMHRII-ADC of Formula (A1) comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the depicted sulfurs are from cysteine residues, for example, C220, C226, and C229 of a heavy chain of the AMHRII antibody according to the EU numbering, and C214 of a light chain of the 10 NAI-1539665006v1AMHRII antibody according to the EU or Kabat numbering, such as ADC-034 as disclosed herein.

[0021] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0022] In one embodiment, the AMHRII-ADC of Formula (I) or a salt of any thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:4, 20, and 23; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:5, 21, and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs:6 and 22; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 19, and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:3.

[0023] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising (i) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (ii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iii) a 11 NAI-1539665006v1VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (ii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3.

[0024] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0025] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising a VH comprising the amino acid sequence as set forth in SEQ ID NO:9.

[0026] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody which comprises one or more IgG1 constant regions. In a further embodiment, the AMHRII antibody is an IgG1 antibody. In one embodiment, the AMHRII- ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14. Additionally or alternatively, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody which comprises a kappa (κ) light chain. In a further embodiment, the 12 NAI-1539665006v1AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12 or 13. Additionally or alternatively, the AMRHII antibody is a human antibody.

[0027] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (A1), or Formula (B1) comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0028] In one embodiment of the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, n is 1. In one embodiment of the AMHRII-ADC of Formula (I) or a salt thereof Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, or Formula (B1), n is 2. In one embodiment of the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, n is 3. In one embodiment of the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, n is 4. In one embodiment of the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, n is 5. In one embodiment of the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, n is 6. In one embodiment of the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, n is 7. In one embodiment of the AMHRII- ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, or Formula (A1), n is 8. 13 NAI-1539665006v1

[0029] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (II):or a salt thereof, wherein: n is an integer from 1 to 8, and Ab represents an antibody that binds to AMHRII (“AMHRII antibody”).

[0030] In some embodiments, the point of attachment to the Ab is through a cysteine or a lysine residue of the antibody. In further embodiments, the point of attachment to the Ab is from two cysteine residues which form an interchain disulfide bridge in an AMHRII antibody when not conjugated as the ADC of Formula (II) or a salt thereof, for example, between two heavy chains (such as C226 and / or C229 accordingly to the EU numbering) or between a heavy chain and a light chain (such as C220 of a heavy chain according to the EU numbering and C214 of a light chain according to the EU or Kabat numbering). Accordingly, n is selected from the group consisting of 2, 4, 6 and 8. In some embodiments, the point of attachment to the Ab is through any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the AMHRII antibody according to the EU numbering. 14 NAI-1539665006v1

[0031] In some embodiments, the ADC is of Formula (II-A) or a salt thereof:. (II-A)

[0032] In other embodiments, the ADC is of Formula (II-B) or a salt thereof:. (II-B) 15 NAI-1539665006v1

[0033] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formulawherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted sulfurs are from cysteine residues (optionally selected from C220, C226, or C229 of a heavy chain of the AMHRII antibody according to the EU numbering, or C214 of a light chain of the AMHRII antibody according to the EU or Kabat numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (A2). 16 NAI-1539665006v1

[0034] In some embodiments, X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (A2).

[0035] In some embodiments, X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (A2). 17 NAI-1539665006v1

[0036] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (B2):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue (optionally any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the AMHRII antibody according to the EU numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof:, wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (B2). 18 NAI-1539665006v1

[0037] In some embodiments, X represents the structure below or a salt thereof:. wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (B2).

[0038] In some embodiments, X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the AMHRII-ADC of Formula (B2).

[0039] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as 19 NAI-1539665006v1set forth in SEQ ID NO:14. In one embodiment, the AMHRII-ADC of Formula (B2) comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering), such as ADC-031 as disclosed herein. In one embodiment, the AMHRII-ADC of Formula (A2) comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the depicted sulfurs are from cysteine residues, for example, C220, C226, and C229 of a heavy chain of the AMHRII antibody according to the EU numbering, and C214 of a light chain of the AMHRII antibody according to the EU or Kabat numbering, such as ADC-032 as disclosed herein.

[0040] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0041] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:4, 20, and 23; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:5, 21, and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs:6 and 22; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 19, and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:3.

[0042] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising (i) a VH region comprising a VH CDR1 20 NAI-1539665006v1comprising the amino acid sequence of SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (ii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iv) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (v) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3.

[0043] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0044] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) 21 NAI-1539665006v1comprises an AMHRII antibody comprising a VH comprising the amino acid sequence as set forth in SEQ ID NO:9.

[0045] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody which comprises one or more IgG1 constant regions. In a further embodiment, the AMHRII antibody is an IgG1 antibody. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II- B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14. Additionally or alternatively, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody which comprises a kappa (κ) light chain. In a further embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12 or 13. Additionally or alternatively, the AMRHII antibody is a human antibody.

[0046] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, Formula (A2), or Formula (B2) comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0047] In one embodiment of the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, n is 1. In one embodiment of the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II- B) or a salt thereof, or Formula (B2), n is 2. In one embodiment of the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, n is 3. In one embodiment of the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, n is 4. In one embodiment of the AMHRII-ADC or a salt thereof of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, n is 5. In one embodiment of the AMHRII- ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a 22 NAI-1539665006v1salt thereof, n is 6. In one embodiment of the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, n is 7. In one embodiment of the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, Formula (II-B) or a salt thereof, or Formula (A2), n is 8.

[0048] In another aspect, the present disclosure provides a composition of one or more of the AMHRII-ADCs of Formula (I), (I-A), (I-B), (II), (II-A), or (II-B) or a salt of each thereof. In some embodiments, the AMHRII antibody is hypofucosylated, for example mAb305 as disclosed herein. In some embodiments, the AMHRII antibody is not hypofucosylated, for example mAb304 as disclosed herein. In some embodiments, the AMHRII antibody is not hypofucosylated, for example mAb303 as disclosed herein.

[0049] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof is hypofucosylated and comprises an AMHRII antibody comprising a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0050] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof is not hypofucosylated and comprises an AMHRII antibody comprising a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0051] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof is not hypofucosylated and comprises an AMHRII antibody comprising a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7.

[0052] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof is hypofucosylated and comprises 23 NAI-1539665006v1an AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In one embodiment, the AMHRII-ADC of Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II-B) or a salt thereof is hypofucosylated and comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0053] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof is not hypofucosylated and comprises an AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In one embodiment, the AMHRII-ADC of Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II-B) or a salt thereof is not hypofucosylated and comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0054] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I- A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof is not hypofucosylated and comprises an AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In one embodiment, the AMHRII-ADC of Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II-B) or a salt thereof is not hypofucosylated and comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12.

[0055] In another aspect, the present disclosure provides a pharmaceutical composition comprising one or more of the AMHRII-ADCs of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, which comprise AMHRII antibodies that are optionally hypofucosylated, or a composition of one or more of the AMHRII-ADCs of Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II-B) or a salt 24 NAI-1539665006v1thereof, which comprise AMHRII antibodies of the composition that are optionally hypofucosylated, and a pharmaceutically acceptable carrier.

[0056] On one embodiment, the pharmaceutical composition is characterized by a drug-to- antibody ratio (“DAR”) of about 1 to about 8. In another embodiment, the pharmaceutical composition is characterized by a drug-to-antibody ratio (“DAR”) of about 1 to about 2. In another embodiment, the pharmaceutical composition is characterized by a drug-to-antibody ratio (“DAR”) of about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2. In another embodiment, the pharmaceutical composition is characterized by a drug-to-antibody ratio (“DAR”) of about 2 to about 8. In another embodiment, the pharmaceutical composition is characterized by a drug-to-antibody ratio (“DAR”) of about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8.0.

[0057] In another aspect, the present disclosure provides a method of treating an AMHRII- related disease in a subject, comprising administering to the subject an AMHRII-ADC according to Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II- B) or a salt thereof, which comprises an AMHRII antibody that is optionally hypofucosylated, a pharmaceutical composition comprising the same and a pharmaceutically acceptable excipient such that the AMHRII-related disease is treated in the subject. In one embodiment, the disease is cancer. In one embodiment, the cancer is a gynecological cancer. In one embodiment, the cancer is selected from ovarian cancer, metastatic ovarian cancer, serous cancer, hypernephroma, endometrioid, colloidal epithelium, prostate cancer, germ cell cancer, endometrial cancer, mixed Müllerian malignant tumor of the uterus, leiomyosarcoma, and endometrial stromal sarcoma. In one embodiment, the cancer is selected from colon cancer; lung cancer (such as non-small cell lung cancer, NSCLC); hepatocellular carcinoma, testis cancer; pancreatic cancer, kidney cancer, breast cancer, thyroid cancer, gastric cancer, adrenal cancer, bladder cancer, and prostate cancer. In one embodiment, the method further 25 NAI-1539665006v1comprises administering a second therapeutic agent to the subject, wherein the second therapeutic agent is an anti-cancer agent.

[0058] In another aspect, the present disclosure provides use of an AMHRII-ADC according to Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II- B) or a salt thereof, which comprises an AMHRII antibody that is optionally hypofucosylated, in the manufacture of a medicament for treating an AMHRII-related disease.

[0059] In another aspect, the present disclosure provides an AMHRII-ADC according to Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II-B) or a salt thereof, which comprises an AMHRII antibody that is optionally hypofucosylated, or the pharmaceutical composition thereof for use in treating an AMHRII-related disease.

[0060] In yet another aspect, the present disclosure provides a method of making an AMHRII-ADC according to Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with a reducing agent; c) contacting the solution of b) with a solution comprising Linker-Drugor salt thereof, wherein the AMHRII-ADC is made.

[0061] In yet another aspect, the present disclosure provides a method of making an AMHRII-ADC according to Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with a reducing agent; 26 NAI-1539665006v1c) contacting the solution of b) with a solution comprising Linker-Drug (2):or salt thereof, wherein the AMHRII-ADC is made.

[0062] In one embodiment, the reducing agent is tris(2 carboxyethyl)phosphine (TCEP).

[0063] In yet another aspect, the present disclosure provides a method of making an AMHRII-ADC according to Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with an affinity peptide conjugated to a thiophenol activation moiety; c) contacting the solution of b) with a solution comprising Linker-Drugor salt thereof, wherein the AMHRII-ADC is made.

[0064] In yet another aspect, the present disclosure provides a method of making an AMHRII-ADC according to Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof the steps of: a) providing a solution comprising the AMHRII antibody; 27 NAI-1539665006v1b) contacting the solution of a) with an affinity peptide conjugated to a thiophenol activation moiety; c) contacting the solution of b) with a solution comprising Linker-Drug (2):or salt thereof, wherein the AMHRII-ADC is made.

[0065] In some embodiments, the affinity peptide is a peptide of SEQ ID NO:15.

[0066] In some embodiments, the affinity peptide conjugated to a thiophenol activation moiety is:.

[0067] In some embodiments, the method comprises an initial step of producing the AMHRII antibody in YB2 / 0 cells, such as mAb305.

[0068] In some embodiments, the method comprises an initial step of producing the AMHRII antibody in CHO cells, such as mAb304 and mAb303. BRIEF DESCRIPTION OF THE DRAWINGS

[0069] FIG. 1 provides an exemplary RP-HPLC analysis result of Linker-Drug (2-A), Linker-Drug (2-B), and Linker-Drug (2) (mixture of Linker-Drug (2-A) and Linker-Drug (2- B)), further described in Example 5.

[0070] FIG. 2 illustrates Linker-Drug (2-B).

[0071] FIGs. 3A-3L show exemplary developability and DAR results for ADC-031, ADC- 032, ADC-033, and ADC-034, further described in Example 13. FIGs. 3A-3D provide hydrophobic interaction chromatography (HIC) results for ADC-031, ADC-032, ADC-033, 28 NAI-1539665006v1and ADC-034, respectively. FIGs.3E-3H provide reverse phase liquid chromatography (RP- HPLC) results for ADC-031, ADC-032, ADC-033, and ADC-034, respectively. FIGs.3I-3L provide size exclusion chromatography (SEC) results for ADC-031, ADC-032, ADC-033, and ADC-034, respectively.

[0072] FIGs.4A-4R provide exemplary SEC-HPLC analysis results of the produced ADC- 301-M (mAb303, Linker-Drug (2), DAR2, FIG.4A), ADC-043-A (mAb303, Linker-Drug (2-A), DAR2, FIG.4B), ADC-044-B (mAb303, Linker-Drug (2-B), DAR2, FIG.4C), ADC- 031-M (mAb304, Linker-Drug (2), DAR2, FIG.4D), ADC-310-A (mAb304, Linker-Drug (2-A), DAR2, FIG.4E), ADC-311-B (mAb304, Linker-Drug (2-B), DAR2, FIG.4F), ADC- 304-M (mAb305, Linker-Drug (2), DAR2, FIG.4G), ADC-305-A (mAb305, Linker-Drug (2-A), DAR2, FIG.4H), ADC-306-B (mAb305, Linker-Drug (2-B), DAR2, FIG.4I), ADC- 302-M (mAb303, Linker-Drug (2), DAR8, FIG.4J), ADC-045-A (mAb303, Linker-Drug (2- A), DAR8, FIG.4K), ADC-046-B (mAb303, Linker-Drug (2-B), DAR8, FIG.4L), ADC- 032-M (mAb304, Linker-Drug (2), DAR8, FIG.4M), ADC-312-A (mAb304, Linker-Drug (2-A), DAR8, FIG.4N), ADC-013-B (mAb304, Linker-Drug (2-B), DAR8, FIG.4O), ADC- 307-M (mAb305, Linker-Drug (2), DAR8, FIG.4P), ADC-308-A (mAb305, Linker-Drug (2-A), DAR8, FIG.4Q), ADC-309-B (mAb305, Linker-Drug (2-B), DAR8, FIG.4R), further described in Example 14.

[0073] FIGs.5A-5R provide exemplary HIC-HPLC analysis results of the produced ADC- 301-M (mAb303, Linker-Drug (2), DAR2, FIG.5A), ADC-043-A (mAb303, Linker-Drug (2-A), DAR2, FIG.5B), ADC-044-B (mAb303, Linker-Drug (2-B), DAR2, FIG.5C), ADC- 031-M (mAb304, Linker-Drug (2), DAR2, FIG.5D), ADC-310-A (mAb304, Linker-Drug (2-A), DAR2, FIG.5E), ADC-311-B (mAb304, Linker-Drug (2-B), DAR2, FIG.5F), ADC- 304-M (mAb305, Linker-Drug (2), DAR2, FIG.5G), ADC-305-A (mAb305, Linker-Drug (2-A), DAR2, FIG.5H), ADC-306-B (mAb305, Linker-Drug (2-B), DAR2, FIG.5I), ADC- 302-M (mAb303, Linker-Drug (2), DAR8, FIG.5J), ADC-045-A (mAb303, Linker-Drug (2- A), DAR8, FIG.5K), ADC-046-B (mAb303, Linker-Drug (2-B), DAR8, FIG.5L), ADC- 032-M (mAb304, Linker-Drug (2), DAR8, FIG.5M), ADC-312-A (mAb304, Linker-Drug (2-A), DAR8, FIG.5N), ADC-013-B (mAb304, Linker-Drug (2-B), DAR8, FIG.5O), ADC- 307-M (mAb305, Linker-Drug (2), DAR8, FIG.5P), ADC-308-A (mAb305, Linker-Drug (2-A), DAR8, FIG.5Q), ADC-309-B (mAb305, Linker-Drug (2-B), DAR8, FIG.5R), further described in Example 14.

[0074] FIGs.6A-6E provide exemplary results of in vitro cytotoxicity assays investigating the effects of ADCs (such as ADC-031, ADC-032, ADC-033, and ADC-034) on COV434- 29 NAI-1539665006v1AMHRII cells, further described in Example 15. Three runs were performed, and the corresponding results are shown in FIG.6A and FIG.6B, FIG.6C and FIG.6D, and FIG. 6E and FIG.6F. FIG.6A, FIG.6C, and FIG.6E compare various concentrations of the tested compounds (such as MMAE, control ADC-001, ADC-031, ADC-032, ADC-033, and ADC-034) after 96 hours of incubation, while corresponding IC50 and maximum inhibition percentages are presented in FIG.6B, FIG.6D, and FIG.6F.

[0075] FIGs.7A-7D report tumor volumes (TV) (FIG.7A, FIG.7C, and FIG.7D) and body weights (BW) (FIG.7B) in COV434-AMHRII xenograft mice. FIG.7A and FIG.7B plot data from the mice treated with ADC-031, ADC-032, ADC-033, or ADC-034, while FIG.7C provides data from the mice treated with ADC-301, ADC-044-B, ADC-302, and ADC-046-B, further described in Example 16. FIG.7D focuses on a subset of data presented in FIG.7C.

[0076] FIGs.8A-8D report tumor volumes (FIG.8A and FIG.8C) and body weights (FIG.8B and FIG.8D) in non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) mice treated with ADC-031 (FIG.8A and FIG.8B), ADC-032 (FIG.8A and FIG. 8B), or ADC-302 (FIG.8C and FIG.8D), further described in Example 17.

[0077] FIG.9 provides exemplary results showing mAb303 bound to COV434-AMHRII cells, further described in Example 19.

[0078] FIG.10 provides exemplary results showing mAb303 was internalized in COV434- AMHRII cells, further described in Example 20.

[0079] FIG.11 provides exemplary results showing mAb303 was translocated to endocytic compartments in COV434-AMHRII cells, further described in Example 21. DETAILED DESCRIPTION

[0080] The present disclosure provides an antibody-drug conjugate (ADC) comprising an antibody that binds to AMHRII and a drug conjugated (directly or indirectly) thereto. Such AMHRII-ADCs are useful in compositions and in methods of treating, preventing, or alleviating an AMHRII-mediated disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition. AMHRII-mediated diseases, disorders, and conditions include cancer, for example, reproductive cancers such as ovarian cancer, serous cancer, hypernephroma, endometrioid, colloidal epithelium, prostate cancer, germ cell cancer, endometrial cancer, mixed Müllerian malignant tumor of the uterus, leiomyosarcoma, and endometrial stromal sarcoma. AMHRII-mediated cancers also include colon cancer; lung cancer (such as NSCLC); hepatocellular carcinoma, testis cancer; pancreatic cancer, kidney cancer, breast cancer, thyroid cancer, gastric cancer, adrenal cancer, bladder cancer, and 30 NAI-1539665006v1prostate cancer. The AMHRII-ADCs described herein comprise an AMHRII antibody conjugated to one or more linker-drug conjugates.

[0081] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited.

[0082] The terms “about” and “approximately” mean within 20%, within 15%, within 10%, within 9%, within 8%, within 7%, within 6%, within 5%, within 4%, within 3%, within 2%, within 1%, or less variation of a given value or range.

[0083] As used herein, comparative terms as used herein, such as reduce, decrease, increase, or any grammatical variation thereof, can refer to certain variation from the reference. In some embodiments, such variation can refer to about 10%, or about 20%, or about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 80%, or about 90%, or about 1 fold, or about 2 fold, or about 3 fold, or about 4 fold, or about 5 fold, or about 10 fold, or about 20 fold, or about 30 fold, or about 40 fold, or about 100 fold or higher than the reference. In some embodiments, such variation can refer to about 1%, or about 2%, or about 3%, or about 4%, or about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10%, or about 20%, or about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 80%, or about 90%, or about 95%, or about 96%, or about 97%, or about 98%, or about 99% of the reference.

[0084] As used in the present disclosure and claims, the singular forms “a,” “an” and “the” include plural forms unless the context clearly dictates otherwise.

[0085] In some embodiments, the terms “first,” “second,” “third,” “fourth” and similar in a component name are used to distinguish and identify more than one component sharing certain identity in their names. For example, “first antibody” and “second antibody” are used to distinguish two antibodies.

[0086] It is understood that wherever embodiments are described herein with the term “comprising” otherwise analogous embodiments described in terms of “consisting of” and / or “consisting essentially of” are also provided. It is also understood that wherever embodiments are described herein with the phrase “consisting essentially of” otherwise analogous embodiments described in terms of “consisting of” are also provided.

[0087] The term “between” as used in a phrase as such “between A and B” or “between A- B” refers to a range including both A and B. 31 NAI-1539665006v1

[0088] The term “and / or” as used in a phrase such as “A and / or B” herein is intended to include both A and B; A or B; A (alone); and B (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0089] The term “optional” or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances wherein the circumstance occurs, and the instances wherein the circumstance does not occur. AMHRII ANTIBODIES

[0090] In order to better understand the disclosure, the definitions and explanations of the relevant terms are provided as follows.

[0091] The term “AMHRII,” “AMHR2, ” “MISRII,” “MISR2,” “Müllerian Inhibiting Substance Type II Receptor,” “Anti-Müllerian Hormone Type II Receptor,” “Anti-Müllerian Hormone Type-2 Receptor,” “AMH Type II Receptor,” “MIS Type II Receptor,” “EC 2.7.11.30,” “AMHR,” “MRII,” or similar terms refers to a polypeptide (“polypeptide” and “protein” are used interchangeably herein) or any native AMHRII from any vertebrate source, including mammals such as primates (e.g., humans, cynomolgus monkey (cyno)), dogs, and rodents (e.g., mice and rats), unless otherwise indicated. The AMH receptor (AMHR or AMHRII) is a serine / threonine kinase with a single transmembrane domain belonging to the family of type II receptors for TGF-beta-related proteins. The term AMHRII encompasses “full-length” AMHRII, as well as any form of AMHRII or any fragment thereof that results from processing in the cell. The term AMHRII also encompasses naturally occurring variants of AMHRII, such as SNP variants, splice variants and allelic variants. Other related AMHRII polypeptides that are also encompassed by the term AMHRII include fragments, derivatives (e.g., substitution, deletion, truncations, and insertion variants), fusion polypeptides, and interspecies homologs that retain AMHRII activity. Orthologs to the AMHRII polypeptide are also well known in the art. Exemplary AMHRII sequences and additional information can be found at HGNC: 465; NCBI Entrez Gene: 269; Ensembl: ENSG00000135409; OMIM®: 600956; and UniProtKB / Swiss-Prot: Q16671, each of which is incorporated herein by reference in its entirety. One exemplary sequence of the human AMHRII is described as SEQ ID NO:16 herein (lacking the signal peptide MLGSLGLWALLPTAVEA (SEQ ID NO:17).

[0092] The term “antibody” (e.g., AMHRII antibody) is used in the broadest sense and encompass any form of antibody that exhibits the desired biological or binding activity. It 32 NAI-1539665006v1covers, but is not limited to, humanized antibodies, fully human antibodies, chimeric antibodies, and single-domain antibodies (sdAbs, comprising just one chain, which is typically similar to a heavy chain, such as VHH), as well as fragments of any of the foregoing as long as they exhibit the desired antigen-binding activity, including, for example, an antibody comprising at least one VHH domain. A conventional antibody comprises a heavy chain(s) and a light chain(s). Heavy chains may be classified into μ, δ, γ, α and ε, which define isotypes of an antibody as IgM, IgD, IgG, IgA and IgE, respectively. A heavy chain can comprise a heavy chain variable region (VH) and a heavy chain constant region (CH). A heavy chain can comprise one or more constant regions, for example, 3 constant regions (CH1, CH2 and CH3). A light chain can comprise a light chain variable region (VL) and a light chain constant region (CL). A VH and a VL region can further be divided into hypervariable regions (called complementary determining regions (CDRs)), which are interspaced by relatively conservative regions (called framework regions (FRW)). A VH and a VL can comprise 3 CDRs (complementarity determining regions) and 4 FRWs (framework regions) in the following order: FRW1, CDR1, FRW2, CDR2, FRW3, CDR3, FRW4 from N-terminal to C-terminal. Antibodies can be of different antibody isotypes, for example, IgG (e.g., IgG1, IgG2, IgG3 or IgG4 subtype), IgA1, IgA2, IgD, IgE or IgM antibody.

[0093] A universal numbering system for hypervariable regions has been developed and widely adopted, ImMunoGeneTics (IMGT®) Information System (Lefranc et al., Dev. Comp. Immunol.2003; 27(1):55-77). IMGT®is an integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. Herein, the CDRs are referred to in terms of both the amino acid sequence and the location within the light or heavy chain. As the “location” of the CDRs within the structure of the immunoglobulin variable region is conserved between species and present in structures called loops, by using numbering systems that align variable region sequences of structural features, CDR and framework residues and are readily identified. This information can be used in grafting and replacement of CDR residues from immunoglobulins of one species into an acceptor framework from, typically, a human antibody. An additional numbering system (AHon) has been developed by Honegger and Plückthun, J. Mol. Biol. 309: 657-670 (2001). Correspondence between the numbering system, including, for example, the Kabat numbering and the IMGT®unique numbering system, is well known to one skilled in the art (see, e.g., Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra) and is also illustrated below. Various systems known in the art or described herein represent different ways of delineating CDRs, and when they are used to 33 NAI-1539665006v1define the same antibody, they are often considered equivalent. An exemplary system, shown herein, combines Kabat and Chothia.

[0094] The term “Fc region” is used to define a C-terminal region of an immunoglobulin heavy chain, including, for example, native sequence Fc regions, recombinant Fc regions, and variant Fc regions. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy chain Fc region is often defined to stretch from an amino acid residue at position Cys226 (according to the EU numbering system), or from Pro230 (according to the EU numbering system) to the carboxyl-terminus thereof. The C- terminal lysine (residue 447 according to the EU numbering system) of the Fc region may be removed, for example, during production or purification of the antibody, or by recombinantly engineering the nucleic acid encoding a heavy chain of the antibody.

[0095] A “functional Fc region” possesses an “effector function” of a native sequence Fc region. Exemplary “effector functions” include C1q binding; complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. Such effector functions generally require the Fc region to be combined with a binding region or binding domain (e.g., an antibody variable region or domain, including a VHH domain) and can be assessed using various assays as disclosed.

[0096] A “native sequence Fc region” comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature, and not manipulated, modified, and / or changed (e.g., isolated, purified, selected, including, or combining with other sequences such as variable region sequences) by a human. Native sequence human Fc regions include a native sequence human IgG1 Fc region (non-A and A allotypes); native sequence human IgG2 Fc region; native sequence human IgG3 Fc region; and native sequence human IgG4 Fc region as well as naturally occurring variants thereof.

[0097] A “variant Fc region” comprises an amino acid sequence which differs from that of a native sequence Fc region by virtue of at least one amino acid modification, (e.g., substituting, addition, or deletion) preferably one or more amino acid substitution(s). In some 34 NAI-1539665006v1embodiments, the variant Fc region has at least one amino acid substitution compared to a native sequence Fc region or to the Fc region of a parent polypeptide, for example, from about one to about ten amino acid substitutions, and preferably from about one to about five amino acid substitutions in a native sequence Fc region or in the Fc region of the parent polypeptide. A variant Fc region can possess at least about 80% homology with a native sequence Fc region and / or with an Fc region of a parent polypeptide, or at least about 90% homology therewith, for example, at least about 95% homology therewith. The variant Fc region herein described herein may have a loss of effector function (e.g., silent Fc).

[0098] The terms "anti-AMHRII antibody" and “AMRHII antibody” are used interchangeably and refer to an antibody directed against AMHRII, for example, against the extracellular domain of AMHRII. In some embodiments, the term "anti-human AMHRII antibody" refers to an antibody directed against human AMHRII, in particular against the extracellular domain of human AMHRII.

[0099] As used herein, "antibody" or "immunoglobulin" have the same meaning and are used interchangeably. The term "antibody" as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, e.g., molecules that contain an antigen binding site that immunospecifically binds an antigen. As such, the term antibody encompasses not only whole antibody molecules, but also variants (including derivatives) of antibodies. In natural antibodies, two heavy chains are linked to each other by disulfide bonds and each heavy chain is linked to a light chain by a disulfide bond. There are two types of light chain, lambda (l) and kappa (k). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE. Each chain contains distinct sequence domains. The light chain includes two domains, a variable domain (VL) and a constant domain (CL). The heavy chain includes four domains, a variable domain (VH) and three constant domains (CH1, CH2 and CH3, collectively referred to as CH). The variable regions of both light (VL) and heavy (VH) chains determine binding recognition and specificity to the antigen. The constant region domains of the light (CL) and heavy (CH) chains confer important biological properties such as antibody chain association, secretion, trans-placental mobility, complement binding, and binding to Fe receptors (FcR). The Fv fragment is the N-terminal part of the Fab fragment of an immunoglobulin and consists of the variable portions of one light chain and one heavy chain. The specificity of the antibody resides in the structural complementarity between the antibody combining site and the antigenic determinant. Antibody combining sites are made up of residues that are primarily from the hypervariable or complementarity determining 35 NAI-1539665006v1regions (CDRs). Occasionally, residues from non-hypervariable or framework regions (FRW) influence the overall domain structure and hence the combining site. Complementarity Determining Regions or CDRs refer to amino acid sequences which together define the binding affinity and specificity of the natural Fv region of a native immunoglobulin binding site. The light and heavy chains of an immunoglobulin each have three CDRs, designated VL CDRI, VL CDR2, VL CDR3 and VH CDRI, VH CDR2, VH CDR3, respectively. An antigen-binding site, therefore, includes six CDRs, comprising the CDR set from each of a heavy and a light chain V region. Framework Regions (FRWs) refer to amino acid sequences interposed between CDRs. In addition, an Fc region comprises a heavy chain CH2 and a heavy chain CH3. In further embodiments, an Fc comprises two chains, each of which comprises a heavy chain CH2 and a heavy chain CH3. In some embodiments, an Fc region comprises, from its N terminus to its C terminus, a hinge region, a heavy chain CH2, and a heavy chain. In some embodiments, an Fc region comprises two chains, each of which comprises, from its N terminus to its C terminus, a hinge region, a heavy chain CH2, and a heavy chain.

[0100] A "hinge", "hinge domain" or "hinge region" or "antibody hinge region" refers to the domain of a heavy chain constant region that joins the CH1 domain to the CH2 domain (Roux et al. J. Immunol.1998161:4083). The hinge provides varying levels of flexibility between the binding and effector regions of an antibody and also provides sites for intermolecular disulfide bonding between the two heavy chain constant regions. In some embodiments, a hinge starts at Glu216 and ends at Gly237 for all IgG isotypes (Roux et al., 1998 J Immunol 161:4083). In some embodiments, a hinge starts at Glu216 and ends at Pro230 for all IgG isotypes (www.imgt.org / IMGTScientificChart / Numbering / Hu_IGHGnber.html).

[0101] As used herein, the term “antibody” or any grammatical variations thereof also include an antibody fragment thereof with the proviso that the antibody fragment still binds to AMRHII. Accordingly, the term “an antibody” or any grammatical variations thereof as used herein can be substituted as “an antibody or fragment thereof,” “an antibody or an antigen- binding fragment thereof,” or any grammatical variation thereof.

[0102] Antibody fragments can in particular be selected from the group consisting of Fv, Fab, F(ab')2, Fab', dsFv, scFv, sc(Fv)2 and diabodies. They may be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact antibodies, according to methods well known to the man skilled in the art. 36 NAI-1539665006v1

[0103] Due to their small size, these antibody fragments can be of high interest for example through their binding to the AMHRII at the hypothalamic level on the GnRH neurons, a major component of PCOS physiopathology.

[0104] "Single-chain Fv" or "scFv" antibody fragments comprise the VH and VL domains of antibody, wherein these domains are present in a single polypeptide chain. Generally, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains, which enables the scFv to form the desired structure for antigen binding. For a review of scFv, see Plückthun in The Pharmacology of Monoclonal Antibodies, Vol 113, Rosenburg and Moore eds. Springer- Verlag, New York, pp.269-315 (1994). The term "diabodies" refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy chain variable domain (VH) connected to a light chain variable domain (VL) in the same polypeptide chain (VH and VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, for example, EP 404,097; WO 1993 / 11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

[0105] Diabodies or bi-specific antibodies (bsAbs) can be roughly divided into two categories: immunoglobulin G (IgG)-like molecules and non-IgG-like molecules. IgG-like bsAbs retain Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP) (Spiess et al., 2015, Mol Immunol., Vol.67(2) : 95-106.). The Fc region of bsAbs facilitates purification and improves solubility and stability. Bi-specific antibodies in IgG-like formats usually have longer serum half-lives owing to their larger size and FcRn-mediated recycling (Kontermann et al., 2015, Bispecific antibodies. Drug Discov. Today Vol.20(7) : 838-47). Non-IgG-like bsAbs are smaller in size, leading to enhanced tissue penetration (Kontermann et al., 2015, Bispecific antibodies, Drug Discov. Today, 20(7): 838-47).

[0106] In some embodiments, any antibody as disclosed herein is a monoclonal antibody. A monoclonal antibody can be a chimeric, humanized, or human antibody. The monoclonal antibodies specified herein specifically include "chimeric" anti-AMHRII antibodies (immunoglobulins) in which a portion of the heavy and / or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another 37 NAI-1539665006v1species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (U.S. Patent No.4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851-6855 (1984)).

[0107] The monoclonal antibodies specified herein also encompass humanized anti- AMHRII antibodies. "Humanized" forms of non-human (e.g., murine) antibodies are chimeric antibodies which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies are typically human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit, or nonhuman primate having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR or FRW) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues which are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. In general, the humanized antibody comprises substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence. The humanized antibody optionally also comprises at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol.2:593-596 (1992). Humanized antibodies may be produced by obtaining nucleic acid sequences encoding CDR domains and constructing a humanized antibody according to techniques known in the art.

[0108] Methods for producing humanized antibodies based on conventional recombinant DNA and gene transfection techniques are well known in the art (See, e.g., Riechmann, L. et al.1988; Neuberger, M. S. et al.1985). Antibodies can be humanized using a variety of techniques known in the art including, for example, CDR-grafting (EP 239,400; PCT publication WO91 / 09967; U.S. Pat. Nos.5,225,539; 5,530,101; and 5,585,089), veneering or resurfacing (EP 592,106; EP 519,596; Padlan, E.A. (1991); Studnicka, G.M. et al. (1994); Roguska, M.A. et al. (1994)), and chain shuffling (U.S. Pat. No.5,565,332). The general recombinant DNA technology for preparation of such antibodies is also known (see European Patent Application EP 125023 and International Patent Application WO 96 / 02576). 38 NAI-1539665006v1

[0109] The monoclonal anti-AMHRII antibodies specified herein further encompass anti- AMHRII human antibodies. A "human antibody" is one which possesses an amino acid sequence which corresponds to that of an antibody produced by a human and / or has been made using any of the techniques for making human antibodies as disclosed herein. This definition of a human antibody specifically excludes a humanized antibody comprising non- human antigen-binding residues. Human antibodies can be produced using various techniques known in the art.

[0110] In one embodiment, the human antibody is selected from a phage library, where that phage library expresses human antibodies (see, e.g., Vaughan et al. Nature Biotechnology 14:309-314 (1996): Sheets et al., Proc. Natl. Acad. Sci.95:6157-6162 (1998)); Hoogenboom and Winter, J. Mol. Biol, 227:381 (1991); Marks et al., J. Mol. Biol, 222:581 (1991)). Human antibodies can also be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio / Technology 10:779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368:812-13 (1994); Fishwild et al., Nature Biotechnology 14: 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); Lonberg and Huszar, Intern. Rev. Immunol.13:65-93 (1995). Alternatively, the human antibody may be prepared via immortalization of human B lymphocytes producing an antibody directed against a target antigen (such B lymphocytes may be recovered from an individual or may have been immunized in vitro). See, e.g., Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.77 (1985); Boemer et al., J. Immunol, 147 (1):86-95 (1991); and U.S. Pat. No.5,750,373.

[0111] The terms "monoclonal antibody" as used herein refer to an antibody obtained from a population of substantially homogeneous antibodies, e.g., the individual antibodies comprising the population are identical except for possible naturally occurring mutations or alternative post-translational modifications that may be present in minor amounts. Monoclonal antibodies are highly specific; in contrast to conventional (polyclonal) antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they are 39 NAI-1539665006v1synthesized by the homogeneous culture, uncontaminated by other immunoglobulins with different specificities and characteristics. For example, monoclonal antibodies may be made by the hybridoma method first described by Kohler et al., Nature 256:495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Patent No.4,816,567). The "monoclonal antibodies" may also be isolated from phage antibody libraries using the techniques described in, e.g., Clackson et al., Nature 352:624-628 (1991) or Marks et al., J. Mol. Biol.222:581- 597 (1991).

[0112] In some embodiments, an antibody as disclosed herein is an antibody mutant or an antibody variant. As used herein, "antibody mutant" or "antibody variant" refers to an amino acid sequence variant of the species-dependent antibody wherein one or more of the amino acid residues of the species-dependent antibody have been modified. Such mutants necessarily have less than 100% sequence identity or similarity with the species-dependent antibody but maintain CDRs with 100% sequence identity with the CDRs of an antibody.

[0113] Identity or similarity with respect to a sequence as mentioned in the present text is defined herein as the percentage of amino acid residues in the candidate sequence that are identical e.g., same residue) or similar (e.g., amino acid residue from the same group based on common side-chain properties, see below) with the species-dependent antibody residues, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. None of N-terminal, C-terminal, or internal extensions, deletions, or insertions into the antibody sequence outside of the variable domain shall be construed as affecting sequence identity or similarity.

[0114] An "antibody heavy chain," as used herein, refers to the larger of the two types of polypeptide chains present in all antibody molecules in their naturally occurring conformations.

[0115] An "antibody light chain," as used herein, refers to the smaller of the two types of polypeptide chains present in all antibody molecules in their naturally occurring conformations. Light chains as used herein refer to any of the two major antibody light chain isotypes, kappa, and lambda. In some embodiments, an AMHRII antibody of an AMHRII- ADC as disclosed herein comprises a kappa light chain.

[0116] As used herein the term "complementarity determining region" or "CDR" refers to the part of the two variable chains of antibodies (heavy and light chains) that recognize and bind to the particular antigen. The CDRs are the most variable portion of the variable chains and provide the antibody with its specificity. There are three CDRs on each of the variable heavy (VH) and variable light (VL) chains and thus there are a total of six CDRs per antibody 40 NAI-1539665006v1molecule. The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a VH CDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a VL CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. An antibody that binds AMHRII has a specific VH region and the VL region sequence, and thus specific CDR sequences. Antibodies with different specificities (e.g., different combining sites for different antigens) have different CDRs. Although it is the CDRs that vary from antibody to antibody, only a limited number of amino acid positions within the CDRs are directly involved in antigen binding. These positions within the CDRs are called specificity determining residues (SDRs).

[0117] As used herein, the percent identity between two amino acid sequences can be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl. Biosci., 4:11-17, 1988) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (J. Mol. Biol.48:444-453, 1970) algorithm which has been incorporated into the GAP program in the GCG software package (available at http: / / www.gcg.com), using either a Blossom 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

[0118] The term “identity,” as used herein, refers to a relationship between the sequences of two or more polypeptide molecules or two or more nucleic acid molecules, as determined by aligning and comparing the sequences. “Percent identity” means the percent of identical residues between the amino acids or nucleotides in the compared molecules and is calculated based on the size of the smallest of the molecules being compared. For these calculations, gaps in alignments (if any) are preferably addressed by a particular mathematical model or computer program (e.g., an “algorithm”). Methods that can be used to calculate the identity of the aligned nucleic acids or polypeptides include those described in Computational Molecular Biology, (Lesk, A. M., ed.), 1988, New York: Oxford University Press; Biocomputing Informatics and Genome Projects, (Smith, D. W., ed.), 1993, New York: Academic Press; Computer Analysis of Sequence Data, Part I, (Griffin, A. M., and Griffin, H. G., eds.), 1994, New Jersey: Humana Press; von Heinje, G., 1987, Sequence Analysis in Molecular Biology, New York: Academic Press; Sequence Analysis Primer, (Gribskov, M. and Devereux, J., 41 NAI-1539665006v1eds.), 1991, New York: M. Stockton Press; and Carillo et al, 1988, SIAMJ. Applied Math. 48:1073. Alignment methods are available to one of skilled in the art, such as BLAST as disclosed herein and / or Clustal Omega.

[0119] “Polynucleotide” or “nucleic acid,” as used interchangeably herein, refers to polymers of nucleotides of any length and includes DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides, or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and their analogs. A cell that produces a binding molecule of the present disclosure may include a parent hybridoma cell, as well as bacterial and eukaryotic host cells into which nucleic acids encoding the antibodies have been introduced. Unless specified otherwise, the left-hand end of any single-stranded polynucleotide sequence disclosed herein is the 5’ end; the left-hand direction of double-stranded polynucleotide sequences is referred to as the 5’ direction. The direction of 5’ to 3’ addition of nascent RNA transcripts is referred to as the transcription direction; sequence regions on the DNA strand having the same sequence as the RNA transcript that are 5’ to the 5’ end of the RNA transcript are referred to as “upstream sequences”; sequence regions on the DNA strand having the same sequence as the RNA transcript that are 3’ to the 3’ end of the RNA transcript are referred to as “downstream sequences.”

[0120] The term “vector,” as used herein, refers to a nucleic acid vehicle which can have a polynucleotide inserted therein. When the vector allows for the expression of the protein encoded by the polynucleotide inserted therein, the vector is called an expression vector. The vector can have carried genetic material elements expressed in a host cell by transformation, transduction, or transfection into the host cell. Vectors are well known by a person skilled in the art, including, but not limited to plasmids, phages, cosmids, artificial chromosome such as yeast artificial chromosome (YAC), bacterial artificial chromosome (BAC) or P1-derived artificial chromosome (PAC); phage such as λ phage or M13 phage and animal virus. The animal viruses that can be used as vectors, include, but are not limited to, retrovirus (including lentivirus), adenovirus, adeno-associated virus, herpes virus (such as herpes simplex virus), pox virus, baculovirus, papillomavirus, papova virus (such as SV40). A vector may comprise multiple elements for controlling expression, including, but not limited to, a promoter sequence, a transcription initiation sequence, an enhancer sequence, a selection element, and a reporter gene. In addition, a vector may comprise an origin of replication. 42 NAI-1539665006v1

[0121] The term “host cell,” as used herein, refers to a cell into which a vector can be introduced, including, but not limited to, a prokaryotic cell such as E. coli or Bacillus subtilis, a fungal cell such as yeast cell or Aspergillus, an insect cell such as S2 Drosophila cell or Sf9, and an animal cell such as fibroblast, CHO cell, COS cell, NSO cell, HeLa cell, BHK cell, HEK 293 cell or human cell.

[0122] The term “transfection” or “transfect,” as used herein, refers to a process by which nucleic acids are introduced into eukaryotic cells, particularly mammalian cells. Protocols and techniques for transfection include but not limited to lipid transfection and chemical and physical methods such as electroporation. A number of transfection techniques are well known in the art and are disclosed herein. See, e.g., Graham et al., 1973, Virology 52:456; Sambrook et al., 2001, Molecular Cloning: A Laboratory Manual, supra; Davis et al., 1986, Basic Methods in Molecular Biology, Elsevier; Chu et al, 1981, Gene 13:197. Antibodies

[0123] In one aspect, the present disclosure provides an AMHRII antibody-drug conjugate (“AMHRII-ADC”) comprising an AMHRII antibody and a linker-drug.

[0124] AMHRII antibodies that may be suitable for use in the AMHRII-ADCs as disclosed herein include those disclosed in U.S. Patent No.9,012,607, WO2008 / 053330A2, WO2013 / 093379A1, WO2018 / 189379A1, WO 2018 / 189381A1, WO2018 / 219956A1, WO2017 / 025458A1, WO2021 / 043849A1 and WO 2021 / 078959 A1, each of which are incorporated herein by reference in its entirety.

[0125] In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9. Additionally or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the amino acid sequence as set forth in SEQ ID NO:7. In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the amino acid sequence as set forth in SEQ ID NO:7. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. In further embodiments, the AMHRII- ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). 43 NAI-1539665006v1

[0126] In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9. Additionally or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. In further embodiments, the AMHRII- ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0127] In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9. Additionally or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VL, wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the amino acid sequence as set forth in SEQ ID NO:7. In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH and a VL, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the amino acid sequence as set forth in SEQ ID NO:7. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. In further embodiments, the AMHRII-ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0128] In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9. Additionally or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VL, wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the 44 NAI-1539665006v1amino acid sequence as set forth in SEQ ID NO:8. In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH and a VL, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 of a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 of a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. In further embodiments, the AMHRII-ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0129] In some embodiments, an AMHRII-ADC as disclosed herein comprises an AMHRII antibody comprising a heavy chain variable domain (VH), wherein the VH comprises or consists of: (a) an amino acid sequence as set forth in SEQ ID NO:9; (b) an amino acid sequence which is at least 85%, at least 90%, or at least 95% identical to SEQ ID NO:9; or (c) an amino acid sequence with addition, deletion and / or substitution of one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) amino acids compared with SEQ ID NO:9.

[0130] In further embodiments, the AMHRII antibody comprises a VH CDR1, a VH CDR2, and a VH CDR3 of SEQ ID NO:9. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. In further embodiments, the AMHRII-ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0131] Additionally, or alternatively, an AMHRII-ADC as disclosed herein comprises an AMHRII antibody comprising a light chain variable domain (VL), wherein the VL comprises or consists of: (a) an amino acid sequence as set forth in SEQ ID NO:7 or 8; (b) an amino acid sequence which is at least 85%, at least 90%, or at least 95% identical to SEQ ID NO:7 or 8; or 45 NAI-1539665006v1(c) an amino acid sequence with addition, deletion and / or substitution of one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) amino acids compared with SEQ ID NO:7 or 8.

[0132] In further embodiments, the AMHRII antibody comprises a VL CDR1, a VL CDR2, and a VL CDR3 of SEQ ID NO:7 or 8. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. In further embodiments, the AMHRII-ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0133] The percent identity between two amino acid sequences can be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl. Biosci., 4:11-17 (1988)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined by the algorithm of Needleman and Wunsch (J. Mol. Biol.48:444-453 (1970)) which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

[0134] Additionally, or alternatively, protein (e.g., antibody) sequences of the present disclosure can further be used as a “query sequence” to perform a search against public databases to, for example, identify related sequences. Such searches can be performed using the XBLAST program (version 2.0) of Altschul, et al. (1990) J. Mol. Biol.215:403-10. BLAST protein searches can be performed with the XBLAST program, score = 50, word length = 3 to obtain amino acid sequences homologous to the antibody molecules of the disclosure. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al, (1997) Nucleic Acids Res.25(17):3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. See www.ncbi.nlm.nih.gov.

[0135] In some embodiments, the amino acid sequence of a VH can be at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any one of SEQ ID NO:9. Additionally or alternatively, the amino acid sequence of a VL can be at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any one of SEQ ID NO:7 or 8. 46 NAI-1539665006v1

[0136] In some further embodiments, AMHRII antibodies may contain conservative substitution or modification of amino acids in the variable regions of the heavy chain and / or light chain, such as VH. It is understood in the art that certain conservative sequence modification can be made which do not remove antigen binding. See, e.g., Brummell et al. (1993) Biochem 32:1180-8; de Wildt et al. (1997) Prot. Eng.10:835-41; Komissarov et al. (1997) J. Biol. Chem.272:26864- 26870; Hall et al. (1992) J. Immunol.149:1605-12; Kelley and O’Connell (1993) Biochem.32:6862-35; Adib-Conquy et al. (1998) Int. Immunol. 10:341-6 and Beers et al. (2000) Clin. Can. Res.6:2835-43.

[0137] As described above, the term “conservative substitution,” as used herein, refers to an amino acid substitution which would not disadvantageously affect or change the essential properties of a protein / polypeptide comprising the amino acid sequence. For example, a conservative substitution may be introduced by standard techniques known in the art such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions include substitutions wherein an amino acid residue is substituted with another amino acid residue having a similar side chain, for example, a residue physically or functionally similar (such as, having similar size, shape, charge, chemical property including the capability of forming covalent bond or hydrogen bond, etc.) to the corresponding amino acid residue. The families of amino acid residues that have similar side chains have been defined in the art. These families include amino acids having alkaline side chains (for example, lysine, arginine and histidine), amino acids having acidic side chains (for example, aspartic acid and glutamic acid), amino acids having uncharged polar side chains (for example, glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), amino acids having nonpolar side chains (for example, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), amino acids having β-branched side chains (such as threonine, valine, isoleucine) and amino acids having aromatic side chains (for example, tyrosine, phenylalanine, tryptophan, histidine). Therefore, a corresponding amino acid residue is preferably substituted with another amino acid residue from the same side-chain family. Methods for identifying amino acid conservative substitutions are well known in the art (see, for example, Brummell et al., Biochem.32: 1180-1187 (1993); Kobayashi et al., Protein Eng. 12(10): 879-884 (1999); and Burks et al., Proc. Natl. Acad. Sci. USA 94: 412-417 (1997), which are incorporated herein by reference).

[0138] In some embodiments, the addition, deletion and / or substitution of at least one of the amino acids is not in any of the CDR sequences, but in the framework (FRW) sequences and / or CH sequences. For example, an antibody or antigen-binding portion thereof as 47 NAI-1539665006v1described above may comprise one or more substitutions of the amino acids in the framework sequences, e.g., FRW1, FRW2, FRW3, and / or FRW4 of the VH and / or VL region.

[0139] In some embodiments, an antibody or antigen-binding portion thereof as provided herein comprises any suitable framework region (FRW) sequences, as long as the antigen- binding domains can specifically bind to AMHRII.

[0140] As described above, an antibody or antigen-binding portion thereof may contain modification of one or more amino acids in the variable regions and / or constant regions, including wherein the modification is a conservative substitution. It is understood in the art that certain conservative sequence modifications can be made which do not remove antigen binding. See, e.g., Brummell et al. (1993) Biochem 32:1180-8; de Wildt et al. (1997) Prot. Eng.10:835-41; Komissarov et al. (1997) J. Biol. Chem.272:26864- 26870; Hall et al. (1992) J. Immunol.149:1605-12; Kelley and O’ Connell (1993) Biochem.32:6862-35; Adib- Conquy et al. (1998) Int. Immunol.10:341-6 and Beers et al. (2000) Clin. Can. Res.6:2835- 43.

[0141] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker-drug, wherein the AMHRII antibody comprises (a) a heavy chain wherein the variable domain comprises: (i) a VH CDR1 having a sequence set forth in any one of SEQ ID NOs:4, 20, and 23; (ii) a VH CDR2 having a sequence set forth in any one of SEQ ID NOs:5, 21, and 24; and (iii) a VH CDR3 having a sequence set forth in SEQ ID NO:6 or 22; and (b) a light chain wherein the variable domain comprises: (i) a VL CDR1 having a sequence set forth in SEQ ID NO:1 and 18; (ii) a VL CDR2 having a sequence set forth in SEQ ID NO:2, 19, and 25; and (iii) a VL CDR3 having a sequence set forth in SEQ ID NO:3.

[0142] In some embodiments, the AMHRII-ADC comprises an antibody comprising at least one VH comprising one, two, and / or three heavy chain CDRs and a VL comprising one, two, and / or three light chain CDRs as described in Table 1A and Table 1B. 48 NAI-1539665006v1QSSA K A)9G Q:P RO K VNQ WDQ )) ) ) )HIYIQ5:Y6:1:2: T3HESNAFO NYO OW:W Y OPOAIS(TSDI RDDRNI VDSNITPDYNISSDIYRFSTVQG ER Q SESQ V)EQWQS7YT:GV S( TSE(S(S(QELS(S:SOSL30A:AT3RN 30KG bCDI3bCSQ G ATITQEAV KW mfVS(mfVY 3 A 12 3oRKoeSFR R R RecDIcARD D D DnGEVn GD C C C CeuHL L L qVSKeuPKGAT qeKRV V V VeSdSiLG GSdVTECcTY SGiFcAY . R APS TA oGSV1qD.oeqniQS CTWPniQA v6VT00LeSm AMY m VLQISSALD56HRE 69VSR35V D W V QL1-IA NQSLSA K A)9G Q:P RO K VNQ WDQ )) ) ) )HIYIQ5:Y6 1 2T3: :HEO: : :SAO O OW:PO5W 0A 50YS(NFDI RN YRNSN 3I3TSDDIVTYNSbYbFSQ GS DI PDI SDIARATVYTER QE SQ mV)EQWQ dS8:md GV S( TSE(S(S(QELS( na SSOnaSL4AT0A3RN 40KG bCDI3bCSQ G ATITQEAV mKW mfVS( fY 31 2 3oRKI o VeSA AFR R R RecD GE cGRD D D DneVne PD C C C Cu VSK uKGHL L L qeAT qeKRV V V VSdSiLGSVTCcTG Gdic EAY ASP F.RTAGY V1qD.o S oeqniQW nSiQATv600SC LeSmTPmVD5AMY VLQISSAL E669HRVS35V D W V QRL1-IA N

[0145] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain variable region having at least 85% identity with the amino acid sequence as set forth in SEQ ID NO:7 or 8 and (i) a VL CDR1 having a sequence set forth in SEQ ID NO:1; (ii) a VL CDR2 having a sequence set forth in SEQ ID NO:2; and (iii) a VL CDR3 having a sequence set forth in SEQ ID NO:3.

[0146] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain variable region having at least 90% identity with the amino acid sequence as set forth in SEQ ID NO:7 or 8 and (i) a VL CDR1 having a sequence set forth in SEQ ID NO:1; (ii) a VL CDR2 having a sequence set forth in SEQ ID NO:2; and (iii) a VL CDR3 having a sequence set forth in SEQ ID NO:3.

[0147] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain variable region having at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence as set forth in SEQ ID NO:7 or 8, and (i) a VL CDR1 having a sequence set forth in SEQ ID NO:1; (ii) a VL CDR2 having a sequence set forth in SEQ ID NO:2; and (iii) a VL CDR3 having a sequence set forth in SEQ ID NO:3.

[0148] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain variable region comprising an amino acid as set forth in SEQ ID NO:7 or 8.

[0149] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain having at least 85% identity with the amino acid sequence as set forth in SEQ ID NO:12 or 13, and (i) a VL CDR1 having a sequence set forth in SEQ ID NO:1; (ii) a VL CDR2 having a sequence set forth in SEQ ID NO:2; and (iii) a VL CDR3 having a sequence set forth in SEQ ID NO:3.

[0150] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain having at least 90% identity with the amino acid sequence as set forth in SEQ ID NO:12 or 13, and (i) a VL CDR1 having a sequence set forth in SEQ ID NO:1; (ii) a VL CDR2 having a sequence set forth in SEQ ID NO:2; and (iii) a VL CDR3 having a sequence set forth in SEQ ID NO:3. 51 NAI-1539665006v1

[0151] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain having at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence as set forth in SEQ ID NO:12 or 13, and (i) a VL CDR1 having a sequence set forth in SEQ ID NO:1; (ii) a VL CDR2 having a sequence set forth in SEQ ID NO:2; and (iii) a VL CDR3 having a sequence set forth in SEQ ID NO:3.

[0152] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a light chain comprising an amino acid as set forth in SEQ ID NO:12 or 13.

[0153] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain variable region having at least 85% identity with the amino acid sequence as set forth in SEQ ID NO:9, and (i) a VH CDR1 having a sequence set forth in SEQ ID NO:4; (ii) a VH CDR2 having a sequence set forth in SEQ ID NO:5; and (iii) a VH CDR3 having a sequence set forth in SEQ ID NO:6.

[0154] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain variable region having at least 90% identity with the amino acid sequence as set forth in SEQ ID NO:9, and (i) a VH CDR1 having a sequence set forth in SEQ ID NO:4; (ii) a VH CDR2 having a sequence set forth in SEQ ID NO:5; and (iii) a VH CDR3 having a sequence set forth in SEQ ID NO:6.

[0155] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain variable region having at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence as set forth in SEQ ID NO:9 and (i) a VH CDR1 having a sequence set forth in SEQ ID NO:4; (ii) a VH CDR2 having a sequence set forth in SEQ ID NO:5; and (iii) a VH CDR3 having a sequence set forth in SEQ ID NO:6.

[0156] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:9. 52 NAI-1539665006v1

[0157] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain having at least 85% identity with the amino acid sequence as set forth in SEQ ID NO:14, and (i) a VH CDR1 having a sequence set forth in SEQ ID NO:4; (ii) a VH CDR2 having a sequence set forth in SEQ ID NO:5; and (iii) a VH CDR3 having a sequence set forth in SEQ ID NO:6.

[0158] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain having at least 90% identity with the amino acid sequence as set forth in SEQ ID NO:14, and (i) a VH CDR1 having a sequence set forth in SEQ ID NO:4; (ii) a VH CDR2 having a sequence set forth in SEQ ID NO:5; and (iii) a VH CDR3 having a sequence set forth in SEQ ID NO:6.

[0159] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain having at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence as set forth in SEQ ID NO:14 and (i) a VH CDR1 having a sequence set forth in SEQ ID NO:4; (ii) a VH CDR2 having a sequence set forth in SEQ ID NO:5; and (iii) a VH CDR3 having a sequence set forth in SEQ ID NO:6.

[0160] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14.

[0161] In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6; and a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3. In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3. In one embodiment, an 53 NAI-1539665006v1AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3. In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3. In one embodiment, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3.

[0162] In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:9. Additionally or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VL comprising the amino acid sequence as set forth in SEQ ID NO:7 or 8. In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL comprising the amino acid sequence as set forth in SEQ ID NO:7. In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In further embodiments, the AMHRII-ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0163] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and a linker- drug, wherein the AMHRII antibody comprises: 54 NAI-1539665006v1a) a light chain comprising or consisting of a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:7 or 8 and a light chain kappa constant region comprising the amino acid sequence as set forth in SEQ ID NO:10; and (b) a heavy chain comprising or consisting of a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:9 and a heavy chain constant region comprising the amino acid sequence as set forth in SEQ ID NO:11.

[0164] In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14. Additionally or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12 or 13. In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12. In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13. In further embodiments, the AMHRII- ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I- A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0165] As it would be understood by one of skill in the art, K447 according to the EU numbering can be cleaved off during antibody production. Accordingly, any AMHRII antibody as disclosed herein can refer to an antibody comprising K447 in both of its heavy chains (if present) or a fragment thereof having the K447 removed in one or both of its heavy chains (if present). In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein lacks K447 according to the EU numbering (e.g., the 445thamino acid residue of SEQ ID NO:14 which is a K). In further embodiments, comprises a heavy chain comprising the 1stamino acid residue to the 444thamino acid residue of SEQ ID NO:14. Additionally or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12 or 13. In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a heavy chain comprising the 1stamino acid residue to the 444thamino acid residue of SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12. In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein comprises a heavy chain comprising the 1stamino acid residue to the 444thamino acid residue of SEQ ID NO:14 and a light chain 55 NAI-1539665006v1comprising the amino acid sequence as set forth in SEQ ID NO:13. In further embodiments, the AMHRII-ADC is of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2).

[0166] Accordingly, also provided is a composition of one or more of the AMHRII-ADC as disclosed herein. In some embodiments, at least one AMHRII antibody of the composition comprises K447 according to the EU numbering. Additionally, or alternatively, at least one AMHRII antibody of the composition lacks K447 according to the EU numbering.

[0167] In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein is an IgG antibody, such as IgG1, IgG2, IgG3 or IgG4. In further embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein is an IgG1 antibody. In some embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein further comprises one or more (such as two, three, or more) constant regions of an IgG, such as IgG1, IgG2, IgG3 or IgG4. In further embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein further comprises one or more (such as two, three, or more) constant regions of an IgG1. In further embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein further comprises an IgG1 Fc region. In yet further embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein further comprises a human IgG1 Fc region. Additionally, or alternatively, an AMHRII antibody of an AMHRII-ADC as disclosed herein further comprises a kappa (κ) light chain. In further embodiments, an AMHRII antibody of an AMHRII-ADC as disclosed herein further comprises a human kappa (κ) light chain.

[0168] An AMHRII-ADC as disclosed herein comprises an AMHRII antibody that further comprises one or more human IgG constant domains. A human IgG constant domain may be a human IgG1, IgG2, IgG3 or IgG4 constant domain, preferably a human IgG1 constant domain. The “EU numbering system” or “EU index” is generally used when referring to a residue in an immunoglobulin heavy chain constant region (e.g., the EU index reported in Kabat et al., supra). See, www.imgt.org / IMGTScientificChart / Numbering / Hu_IGHGnber.html.

[0169] An AMHRII-ADC as disclosed herein comprises an AMHRII antibody that comprises a kappa (κ) light chain or a lambda (λ) light chain, preferably a kappa (κ) light chain. The “EU numbering system” or “EU index” can also be used when referring to a residue in an immunoglobulin kappa light chain. See, e.g., www.imgt.org / IMGTScientificChart / Numbering / Hu_IGKCnber.html. With respect to a kappa light chain, Kabat numbering might also be used herein. Also see, www.imgt.org / IMGTScientificChart / Numbering / Hu_IGKCnber.html for a kappa light chain. As 56 NAI-1539665006v1this webpage shows, C214 of a kappa light chain according to the EU numbering is C214 according to the Kabat numbering. With respect to lambda light chain, Kabat numbering is available. See, www.imgt.org / IMGTScientificChart / Numbering / Hu_IGLCnber.html.

[0170] Accordingly, unless stated otherwise herein, references to residue numbers in an antibody heavy chain or a fragment thereof means residue numbering by the EU numbering system. Unless stated otherwise herein, references to residue numbers in an antibody light chain or a fragment thereof means residue numbering by the EU and / or Kabat numbering system. In some embodiments, references to residue numbers in an antibody kappa light chain or a fragment thereof means residue numbering by the EU numbering system. In some embodiments, references to residue numbers in an antibody lambda light chain or a fragment thereof means residue numbering by the Kabat numbering system.

[0171] Modifications of antibodies are also included within the scope of the present disclosure. Covalent modifications include reacting targeted amino acid residues of an antibody with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C- terminal residues of the antibody, such as those disclosed herein. Other modifications include deamidation of glutaminyl and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the α-amino groups of lysine, arginine, and histidine side chains (see, e.g., Creighton, Proteins: Structure and Molecular Properties 79-86 (1983)), glycosylation (such as N-linked glycosylation), isomerization of Asp, oxidation, acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group. Hypofucosylation

[0172] AMHRII antibodies, as disclosed herein, comprise an Fc domain comprising an N- glycan. In certain embodiments, the N-glycan is an N-linked biantennary glycan present in the CH2 domain of the immunoglobulin constant (Fc) region (e.g., at EU position 297).”N-glycans” are attached at an amide nitrogen of an asparagine or an arginine residue in a protein via an N- acetylglucosamine residue. These “N-linked glycosylation sites” occur in the peptide primary structure containing, e.g., the amino acid sequence asparagine-X-serine / threonine, where X is any amino acid residue except proline and aspartic acid. Such N-Glycans are fully described in, e.g., Drickamer, K and Taylor, M. E. (2006). Introduction to Glycobiology, 2nded., which is incorporated herein by reference in its entirety. In one embodiment, “N glycan” refers to the Asn- 297 N-linked biantennary glycans present in the CH2 domain of the immunoglobulin constant (Fc) region. 57 NAI-1539665006v1

[0173] In one embodiment, AMHRII-ADCs as disclosed herein comprise hypofucosylated AMHRII antibodies. In some embodiments, hypofucosylated AMHRII antibodies are used in making an AMHRII-ADC as disclosed herein. In another embodiment, AMHRII-ADCs as disclosed herein comprise AMHRII antibodies which are not hypofucosylated. In some embodiments, AMHRII antibodies which are not hypofucosylated are used in making an AMHRII-ADC as disclosed herein.

[0174] A “hypofucosylated” antibody refers to an antibody population in which less than 50% of the N-linked oligosaccharide chains contain α1,6-fucose attached to the CH2 domain. Typically, less than about 40%, less than about 30%, less than about 20%, less than about 10%, or less than 5% or less than 1% of the N-linked oligosaccharide chains contain α1,6-fucose attached to the CH2 domain in a “hypofucosylated” antibody preparation. As used herein, an antibody population in which less than 50% of the N-linked oligosaccharide chains contain α1,6- fucose attached to the CH2 domain encompasses a preparation, wherein less than 49%, 48%, 47%, 46%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or less than 1% of the N- linked oligosaccharide chains contain al,6-fucose attached to the CH2 domain. Umana et al., Nat. Biotechnol.17: 176-180, 1999, which describes bisected GlcNac resulting in 10 times ADCC. Umana notes that such bisected molecules result in less fucosylation. Davies et al, Biotechnol. Bioeng.74:288-294, 2001 describe CHO cells with inserted enzyme β1-4-N- acetylglucosaminyltransferase III (GnTIII) (which causes the bisected GlcNac structure) resulting in increased ADCC of anti-CD20 antibodies. Illustratively, the United States Patent No. US 6,602,684 describes cells engineered to produce bisecting GlcNac glycoproteins. Further examples of methods to reduce fucosylation of an antibody preparation are provided in Shields et al., J Biol Chem 277:26733-26740, 2002, which describes CHO cells (Led 3) deficient in fucosylation to produce IgG1 and further describes that binding of the fucose-deficient IgG1 to human Fc gamma RIIIA was improved up to 50-fold and increased ADCC. In addition, Shinkawa et al., J Biol Chem 278:3466-3473, 2003; compare IgG produced in YB2 / 0 and CHO cells. The YB2 / 0 cells have decreased fucosylation and increased bisecting GlcNac content. Niwa et al., Clinical Cancer Res.1:6248-6255, 2004 compare anti-CD20 antibodies with antibodies made in YB2 / 0 cells (low fucosylation) and observed enhanced ADCC in the latter. Examples of techniques to produce afucosylated antibodies are provided, for example, in Kanda et al., Glycobiology 17: 104-118, 2006. U.S. Pat. No.6,946,292 (Kanda) describes fucosyltransferase knock-out cells to produce afucosylated antibodies. The United States Patent 58 NAI-1539665006v1No.7,214,775 and the PCT Publication No. WO 00 / 61739 describe antibody preparations in which 100% of the antibodies are afucosylated.

[0175] Still further techniques to modify glycosylation are also known, such as those described in the United States Patent Publication Nos. US 2007 / 248600A1; US 2007 / 178551A1 (GlycoFi technology methods employing engineered lower eukaryotic cells (yeast) to produce “human” glycosylation structures); US 2008 / 060092A1 (Biolex technology methods employing engineered plants to produce “human” glycosylation structures) and US 2006 / 253928A1 (which also described engineering of plants to produce “human” antibodies). Additional techniques for reducing fucose include ProBioGen technology (von Horsten et al., Glycobiology, (advance access publication Jul.23, 2010); Potelligent™ technology (Biowa, Inc. Princeton, N.J.); and GlycoMAb™ glycosylation engineering technology (GLYCART biotechnology AG, Zurich, Switzerland). The N-linked oligosaccharide content of an antibody can be analyzed by methods known in the art. The following is an example of such a method: Antibodies are subjected to digestion with the enzyme N-glycosidase F (Roche; TaKaRa). Released carbohydrates are analyzed by matrix assisted laser desorption / ionization time-of- flight mass spectrometry (MALDI-TOF MS) with positive ion mode (Papac et al., Glycobiol.8: 445-454, 1998). Monosaccharide composition is then characterized by modified high-performance anion exchange chromatography (HPAEC) (Shinkawa et al., J. Biol. Chem.278: 3466-3473, 2003).

[0176] In one embodiment, the AMHRII-ADC is an AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof and comprises a hypofucosylated AMHRII antibody comprising a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0177] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. Additionally, or alternatively, the AMHRII-ADC comprises an 59 NAI-1539665006v1AMHRII antibody produced in YB2 / 0 cells, for example mAb305. In yet further embodiments, also provided is a composition comprising the AMHRII-ADC and AMHRII antibodies of the AMHRII-ADC composition are hypofucosylated, for example mAb305.

[0178] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. Additionally, or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in CHO cells, for example mAb304. In yet further embodiments, also provided is a composition comprising the AMHRII-ADC and the AMHRII antibodies of the AMHRII-ADC composition are not hypofucosylated, for example mAb304.

[0179] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7. In some embodiments, the CDRs are determined using any one or more of the following methods: IMGT, Kabat, AbM, Chothia, or Contact. See, for example Table 1A and Table 1B. Additionally, or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in CHO cells, for example mAb303. In yet further embodiments, also provided is a composition comprising the AMHRII-ADC and the AMHRII antibodies of the AMHRII-ADC composition are not hypofucosylated, for example mAb303.

[0180] In one embodiment, the AMHRII-ADC is an AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt of each thereof and comprises a hypofucosylated AMHRII antibody comprising (i) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID 60 NAI-1539665006v1NO:1, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (ii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iv) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (v) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3. In some embodiments, mAb303 is produced using CHO cells (accordingly considered herein as not hypofucosylated). In other embodiments, an antibody having the same sequences of mAb303 is produced using YB2 / 0 cells (accordingly considered herein as hypofucosylated). Additionally, or alternatively, mAb304 is produced using CHO cells (accordingly considered herein as not hypofucosylated) and mAb305 is produced using YB2 / 0 cells (accordingly considered herein as hypofucosylated).

[0181] In one embodiment, the AMHRII-ADC is an AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof and comprises a hypofucosylated AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. Additionally or alternatively, the hypofucosylated AMHRII antibody comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:9. 61 NAI-1539665006v1

[0182] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. Additionally or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in YB2 / 0 cells, for example mAb305. In yet further embodiments, also provided is a composition comprising the AMHRII-ADC and AMHRII antibodies of the AMHRII-ADC composition are hypofucosylated, for example mAb305.

[0183] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. Additionally or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in CHO cells, for example mAb304. In yet further embodiments, also provided is a composition comprising the AMHRII-ADC and the AMHRII antibodies of the AMHRII-ADC composition are not hypofucosylated, for example mAb304.

[0184] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL comprising the amino acid sequence as set forth in SEQ ID NO:7. Additionally or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in CHO cells, for example mAb303. In yet further embodiments, also provided is a composition comprising the AMHRII-ADC and the AMHRII antibodies of the AMHRII-ADC composition are not hypofucosylated, for example mAb303.

[0185] In one embodiment, the AMHRII-ADC is an AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof and comprises a hypofucosylated AMHRII antibody a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13. 62 NAI-1539665006v1

[0186] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13. Additionally or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in YB2 / 0 cells, for example mAb305. In yet further embodiments, also provided is a composition comprising the AMHRII- ADC and AMHRII antibodies of the AMHRII-ADC composition are hypofucosylated, for example mAb305.

[0187] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13. Additionally or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in CHO cells, for example mAb304. In yet further embodiments, also provided is a composition comprising the AMHRII- ADC and the AMHRII antibodies of the AMHRII-ADC composition are not hypofucosylated, for example mAb304.

[0188] In some embodiments, provided is an AMHRII-ADC of any one or more of the following formulas or salts thereof: Formula (I), Formula (I-A), Formula (I-B), Formula (A1), Formula (B1), Formula (II), Formula (II-A), Formula (II-B), Formula (A2), or Formula (B2). In further embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12. Additionally or alternatively, the AMHRII-ADC comprises an AMHRII antibody produced in CHO cells, for example mAb303. In yet further embodiments, also provided is a composition comprising the AMHRII- ADC and the AMHRII antibodies of the AMHRII-ADC composition are not hypofucosylated, for example mAb303. Nucleic Acids

[0189] A nucleic acid molecule encoding an AMHRII antibody as disclosed herein can be readily selected by one of skill in the art. In one aspect, the AMHRII antibody of the AMHRII- ADC provided herein may be generated using a first nucleic acid sequence encoding the amino 63 NAI-1539665006v1acid sequence as set forth in SEQ ID NO:14 and a second nucleic acid sequence encoding the amino acid sequence as set forth in SEQ ID NO:12 or 13. Host Cells

[0190] In another aspect, the present disclosure provides a host cell which has been transfected, infected, or transformed by a nucleic acid comprising or consisting of a sequence encoding for the light chain of an AMHRII antibody as disclosed herein and / or comprising or consisting of a sequence encoding for the heavy chain of an AMHRII antibody as disclosed herein or a vector containing the same.

[0191] The term "transformation" means the introduction of a "foreign" (e.g., extrinsic, or extracellular) gene, DNA or RNA sequence to a host cell, so that the host cell expresses the introduced gene or sequence to produce a desired substance, typically a protein or enzyme coded by the introduced gene or sequence, and in particular the antibody. A host cell that receives and expresses introduced DNA or RNA bas been "transformed".

[0192] A nucleic acid comprising or consisting of a sequence encoding for the light chain of an AMHRII antibody as disclosed herein and / or comprising or consisting of a sequence encoding for the heavy chain of an AMHRII antibody as disclosed herein may be used to produce an AMHRII antibody, or a fragment thereof, in a suitable expression system. The term "expression system" means a host cell and compatible vector under suitable conditions, e.g., for the expression of a protein coded for by foreign DNA carried by the vector and introduced to the host cell.

[0193] Common expression systems include E. coli host cells and plasmid vectors, insect host cells and Baculovirus vectors, and mammalian host cells and vectors. Other examples of host cells include, without limitation, prokaryotic cells (such as bacteria) and eukaryotic cells (such as yeast cells, mammalian cells, insect cells, plant cells, etc.). Specific examples include E.coli, Kluyveromyces or Saccharomyces yeasts, mammalian cell lines (e.g., Vero cells, CHO cells, 3T3 cells, COS cells, etc.) as well as primary or established mammalian cell cultures (e.g., produced from lymphoblasts, fibroblasts, embryonic cells, epithelial cells, nervous cells, adipocytes, etc.). Examples also include mouse SP2 / 0-Ag14 cell (ATCC CRL1581), mouse P3X63-Ag8.653 cell (ATCC CRL1580), CHO cell in which a dihydrofolate reductase gene (hereinafter referred to as "DHFR gene") is defective (Urlaub, G. et al.; 1980), rat YB2 / 3HL.P2.G 11.16Ag.20 cell (ATCC CRL1662), and the like.

[0194] In one embodiment, AMHRII-ADCs comprise AMHRII antibodies produced in a cultured mammalian host cell line (e.g., a CHO cell line or YB2 / 0 cell). In certain embodiments, the host cell line has been glycoengineered to produce hypoglycosylated antibodies. In certain 64 NAI-1539665006v1exemplary embodiments, the AMHRII antibodies are obtained from a CHO cell, which is not glycoengineered, such as mAb304. As used herein, CHO cells refer to Chinese hamster ovary cells, see for example, www.atcc.org / products / ccl-61. In certain exemplary embodiments, the AMHRII antibodies are obtained from YB2 / 0 cells, such as mAb305. In some embodiments, YB2 / 0 cells as used herein refers to a rat hybridoma cell line commercially available as ATCC CRL-1662. See, for example, www.atcc.org / products / crl-1662. It has been shown in the art that YB2 / 0 cells produce antibodies with a lower fucose content than those by CHO or NS0 cells. See, for example, Konno et al. Cytotechnology.2012 May;64(3):249-65. In some embodiments, YB2 / 0 cells refer to EMABling® cells, commercially available at www.lfbbiomanufacturing.com / development-services / emabling-platform / .

[0195] As used herein, the term "glycoengineering" refers to any art-recognized method for altering the glycoform profile of an antibody. Such methods include expressing an antibody composition in a genetically engineered host cell (e.g., YB2 / 0 cell) that has been genetically engineered to express a heterologous glycosyltransferase or glycosidase. In other embodiments, the glycoengineering methods comprise culturing a host cell under conditions that bias for particular glycoform profiles. One skilled in the art may refer to well-known techniques for obtaining hypofucosylated antibodies that are known to bind to receptors with a higher affinity than non-modified antibodies.

[0196] While not wishing to be bound by theory, it is believed that incorporating hypofucosylated AMHRII antibodies into the AMHRII-ADCs disclosed herein reduce or block immunosuppression, especially inhibition of the activation of T cells. Vectors

[0197] In another aspect, the present disclosure provides an expression vector comprising at least one nucleic acid comprising or consisting of a sequence encoding for the light chain of an AMHRII antibody as disclosed herein and / or comprising or consisting of a sequence encoding for the heavy chain of an AMHRII antibody as disclosed herein.

[0198] “Expression vector” is used herein to refer to a DNA molecule that has elements permitting its replication (duplication) in at least one living organism. These elements permitting replication are in particular origins of replication in yeast or bacteria, or elements controlling the replication of a virus.

[0199] Suitable vectors that may be used according to the methods disclosed herein include plasmids, phages, yeast artificial chromosomes (YAC), bacterial artificial chromosomes (BAC), modified genomes of replicative viruses or of integrative viruses etc. 65 NAI-1539665006v1

[0200] These vectors are called “expression vectors” as they have nucleotide sequences that permit the expression, e.g., the transcription to RNA, of the nucleotide sequences that they control.

[0201] The nucleic acid sequence contained in said vector is placed “under the control of the elements permitting its expression.” This means that said expression vector has at least one transcription initiation sequence such as a promoter of a virus, for instance the early promoter of the simian virus SV40, or of the Cytomegalovirus (CMV) or the promoter sequences of the Rous sarcoma virus (RSV), and in particular a sequence or promoter comprising a TATAA box. Moreover, said vector also has at least one transcription termination sequence, and in particular a polyadenylation sequence, derived from a mammalian, in particular human, gene.

[0202] To these sequences, which are indispensable for expression of the nucleotide sequence contained in said vector, other sequences may be added for regulating or modulating the expression of said sequence. A non-limitative list comprises introns of mammalian, and in particular human, genes, sequences for regulating transcription of the enhancer type or sequences of mammalian, and in particular human, genes that have been transcribed but not translated.

[0203] When recombinant expression vectors encoding an antibody are introduced into mammalian host cells, the antibody is produced by culturing the host cells for a period of time sufficient to allow for expression of the antibody in the host cells or, secretion of the antibody into the culture medium in which the host cells are grown. Antibodies can be recovered from the culture medium using standard protein purification methods. LINKER-DRUG CONJUGATES

[0204] The AMHRII-ADCs comprises an AMHRII antibody conjugated to a drug via a linker. The linker and drug may be collectively referred to as a “linker-drug” herein.

[0205] In one embodiment, the linker structure is:66 NAI-1539665006v1or a salt thereof, wherein the wavy line represents the point of attachment to the drug. In further embodiments, the linker structure is an (R)-epimer of the linker structure above or a salt thereof. Accordingly, the linker structure isor a salt thereof. In other embodiments, the linker structure is an (S)-epimer of the linker structure above or a salt thereof. Accordingly, the linker structure isor a salt thereof.

[0206] In one embodiment, the drug is an auristatin, for example, MMAE. The structure of MMAE is provided below:67 NAI-1539665006v1MMAE is also known as (2S)-N-[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1- hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3- methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2- (methylamino)butanamide.

[0207] In one embodiment, the drug is a topoisomerase inhibitor, for example, camptothecin or a derivative thereof, such as Exatecan. The structure of Exatecan is provided below:, which is also known as (1S,9S)-1-amino-9-ethyl-5-fluoro-9-hydroxy-4-methyl-1,2,3,9,12,15- hexahydro-10H,13H-benzo[de]pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-10,13-dione.

[0208] In one embodiment, the linker-drug is Linker-Drug (1):or a salt thereof, wherein “Ac” is an acetyl group. Linker-Drug (1) (or a salt thereof) comprises a linker conjugated to monomethyl auristatin E (MMAE). In further embodiments, the linker-drug is an (R)-epimer of Linker-Drug (1) or a salt thereof. Accordingly, the linker-drug is 68 NAI-1539665006v1, (which is also referred to herein as Linker-Drug (1) Form A or Linker-Drug (1-A)) or a salt thereof. In other embodiments, the linker-drug is an (S)-epimer of Linker-Drug (1) or a salt thereof. Accordingly, the linker-drug is 69 NAI-1539665006v1, (which is also referred to herein as Linker-Drug (1) Form B or Linker-Drug (1-B)) or a salt thereof.

[0209] In one embodiment, the linker-drug is Linker-Drug (2):or a salt thereof, wherein “Ac” is an acetyl group. Linker-Drug (2) (or a salt thereof) comprises a linker conjugated to Exatecan. In further embodiments, the linker-drug is an (R)-epimer of Linker-Drug (2) or a salt thereof. Accordingly, the linker-drug is 70 NAI-1539665006v1, (which is also referred to herein as Linker-Drug (2) Form A or Linker-Drug (2-A)) or a salt thereof. In other embodiments, the linker-drug is an (S)-epimer of Linker-Drug (2) or a salt thereof. Accordingly, the linker-drug is, (which is also referred to herein as Linker-Drug (2) Form B or Linker-Drug (2-B)) or a salt thereof.

[0210] Other suitable linker-drug can be found in the international PCT patent application nos. PCT / JP2021 / 162299, PCT / JP2022 / 036852 (international patent application publication no. WO2023054714 published April 6, 2023) and PCT / JP2022 / 036835 (international patent 71 NAI-1539665006v1application publication no. WO2023054706 published April 6, 2023), each of which is incorporated herein by reference in its entirety.

[0211] As used herein, the term “salt” includes, for example, salts of inorganic acids, salts of organic acids, salts of inorganic bases, salts of organic bases, and salts of amino acids. Examples of salts of inorganic acids include salts of hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, and nitric acid. Examples of salts of organic acids include salts of with formic acid, acetic acid, trifluoroacetic acid, lactic acid, tartaric acid, fumaric acid, oxalic acid, maleic acid, citric acid, succinic acid, malic acid, benzenesulfonic acid, and p-toluenesulfonic acid. Examples of salts of inorganic bases include salts of alkali metals (e.g., sodium, potassium), alkaline earth metals (e.g., calcium, magnesium), other metals such as zinc and aluminum, and ammonium. Examples of salts of organic bases include salts of trimethylamine, triethylamine, propylene diamine, ethylenediamine, pyridine, ethanolamine, monoalkyl ethanolamines, dialkyl ethanolamines, diethanolamine, and triethanolamine. Examples of salts of amino acids include salts of basic amino acids (e.g., arginine, histidine, lysine, ornithine) and acidic amino acids (e.g., aspartic acid, glutamic acid). The salt is preferably a salt of an inorganic acid (e.g., hydrogen chloride) or a salt of an organic acid (e.g., trifluoroacetic acid). Antibody-Linker-Drug Conjugation

[0212] In some embodiments, the antibody can be modified before conjugation to the linker- drug. Modification of the antibody can produce a modified antibody that contains one or more reactive groups suitable for conjugation to the linker-drug.

[0213] In some embodiments, the antibody can be modified at one or more amino acid residues to provide one or more reactive groups suitable for conjugation to the linker-drug. For example, amino acid residues and side chains thereof in the antibody can be chemically modified, as described below, and conjugated to a linker-drug. In certain embodiments, the point of attachment of the linker-drug (e.g., drug conjugate moiety) to the Ab is through a cysteine or a lysine residue of the AMHRII antibody, as described below.

[0214] Chemical Conjugation at Lysine Residue

[0215] In some embodiments, the antibody can be conjugated to a linker-drug using chemical conjugation by affinity peptide (CCAP) methods disclosed in US Patent Application Publication No.20210139549A1 (Ajinomoto Co. Inc.), which is incorporated herein by reference in its entirety. In particular, a lysine residue of an AMHRII antibody as disclosed herein may be chemically modified by contacting the AMHRII antibody with an affinity peptide conjugated to a thiophenol-activation moiety to react the thiophenol with the lysine residue on the antibody to 72 NAI-1539665006v1conjugate the affinity peptide to the lysine via a peptide bond as shown below in SCHEMES 1 and 2: .

[0216] The bond between the carboxyl (C=O) and sulfur may then be cleaved to yield a modified lysine residue with a terminal sulfhydryl group as shown below in SCHEME 2:. SCHEME 2 73 NAI-1539665006v1

[0217] The modification may occur at a lysine on each chain of the antibody (e.g., K246 or K248 according to the EU numbering), thereby resulting in two conjugation sites as shown in SCHEME 3 below:. SCHEME 3

[0218] In some embodiments, the lysine residue being modified is any one or more of positions 246, 248, 288, 290, or 317 according to EU numbering (also referred to herein as K246, K248, K288, K290, or K317, respectively). In further embodiments, the lysine residue is K246 and / or K248 according to EU numbering. In yet further embodiments, the lysine residue is K248 accordingly to EU numbering.

[0219] As used herein, K246, K248, K288, K290, or K317 refer to amino acid residues (lysine, Lys, K) of an immunoglobulin identified according to the EU numbering. As it would be understood by one of skill in the art, such numberings accordingly represent amino acid residues of a polypeptide aligned to those identified in an immunoglobulin, such as the one shown in www.imgt.org / IMGTScientificChart / Numbering / Hu_IGHGnber.html. For example, in some embodiments, K246 refers to the 129thamino acid residue of SEQ ID NO:11 which is lysine, K248 refers to the 131stamino acid residue of SEQ ID NO:11 which is also lysine, K288 refers to the 171stamino acid residue of SEQ ID NO:11, K290 refers to the 173rdamino acid residue of SEQ ID NO:11, and K317 refers to the 200thamino acid residue of SEQ ID NO:11. In another 74 NAI-1539665006v1embodiment, K246 refers to the 244thamino acid residue of SEQ ID NO:14 which is lysine, K248 refers to the 246thamino acid residue of SEQ ID NO:14 which is also lysine, K288 refers to the 286thamino acid residue of SEQ ID NO:14, K290 refers to the 288thamino acid residue of SEQ ID NO:14, and K317 refers to the 315thamino acid residue of SEQ ID NO:14.

[0220] Accordingly, provided herein is an AMHRII antibody having a side chain lysyl (- (CH2)4NH2) of one or more of its lysine residues modified to -(CH2)4NHCO(CH2)2SH, for example, as depicted in SCHEME 3. In some embodiments, the AMHRII antibody comprises a VH comprising a CDR1, CDR2, and CDR3 as disclosed herein. In further embodiments, the AMHRII antibody comprises a VH as disclosed herein. In yet further embodiments, the AMHRII antibody comprises a heavy chain as disclosed herein, for example, comprising an amino acid sequence as set forth in SEQ ID NO:14. Additionally, or alternatively, the modified lysine residue is selected from one or more of the following: K246, K248, K288, K290, or K317. In further embodiments, the modified lysine residue is K246 and / or K248. In yet further embodiments, the modified lysine residue is K248. Theses modified AMHRII antibodies are useful, for example, as synthetic intermediates in the production of an AMHRII-ADC as disclosed herein.

[0221] The terminal sulfhydryl group may be reacted with a maleimide moiety on a linker- drug, such as the maleimide moiety on Linker-Drug (1) (or a salt thereof), Linker-Drug (1-A) (or a salt thereof), Linker-Drug (1-B) (or a salt thereof), Linker-Drug (2) (or a salt thereof), Linker- Drug (2-A) (or a salt thereof), or Linker-Drug (2-B) (or a salt thereof) to conjugate the linker- drug thereto as follows according to SCHEME 4: 75 NAI-1539665006v1. SCHEME 4

[0222] In some embodiments, K248 of both heavy chains of an AMHRII antibody was modified and conjugated to a linker-drug as disclosed herein. Accordingly, n in Formula (I), (I- A), (I-B), (II), (II-A), or (II-B) is 2. See, for example, ADC-031, ADC-033, ADC-301, ADC- 043-A, and ADC-044-B.

[0223] In one embodiment, the present disclosure provides a method of making an AMHRII- ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, as disclosed herein, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with an affinity peptide conjugated to a thiophenol activation moiety; c) contacting the solution of b) with a solution comprising Linker-Drug (1) or a salt thereof: 76 NAI-1539665006v1wherein the AMHRII-ADC is made. In some embodiments, the Linker-Drug (1) is Linker-Drug (1-A). In some embodiments, the Linker-Drug (1) is Linker-Drug (1-B). In some embodiments, the Linker-Drug (1) is a mixture of Linker-Drug (1-A) and Linker-Drug (1-B).

[0224] In another embodiment, the present disclosure provides a method of making an AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II- B) or a salt thereof, as disclosed herein, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with an affinity peptide conjugated to a thiophenol activation moiety; c) contacting the solution of b) with a solution comprising Linker-Drug (2) or a salt thereof:wherein the AMHRII-ADC is made. In some embodiments, the Linker-Drug (2) is Linker-Drug (2-A). In some embodiments, the Linker-Drug (2) is Linker-Drug (2-B). In some embodiments, the Linker-Drug (2) is a mixture of Linker-Drug (2-A) and Linker-Drug (2-B). 77 NAI-1539665006v1

[0225] In one embodiment, the affinity peptide is a peptide of SEQ ID NO:15. In one embodiment, the affinity peptide conjugated to a thiophenol activation moiety is:, wherein Ac is an acetyl moiety and the lines linking the sulfurs of the cysteine residues represent a disulfide bridge. Other suitable affinity peptides and thiophenol activation moieties can be found, for example, in US Patent Application Publication No.20210139549A1.

[0226] Stochastic Conjugation of Reduced Interchain Disulfide Bonds

[0227] In some embodiments, the AMHRII antibody is conjugated to a linker-drug via stochastic conjugation to reduced interchain disulfide bonds in the antibody. For example, an IgG1 antibody consists of four polypeptide chains, two heavy chains comprising VH, CH1 and Fc (e.g., hinge, CH2 and CH3) domains, and two light chains comprising VL and CL domains, connected by interchain cysteine disulfide (-S-S-) bonds (e.g., two heavy chain-light chain interchain disulfide bonds and two hinge heavy chain-heavy chain interchain disulfide bonds). In certain embodiments, when these disulfide bonds are broken under reducing conditions, eight (8) reactive cysteine sulfhydryl moieties are produced. In certain embodiments, each of the eight reactive cystine sulfhydryl moieties is a point of attachment for a linker-drug, such that a maximum of eight (n = 8) linker-drugs may be attached to the reduced antibody. See, for example, ADC-032, ADC-034, ADC-302, ADC-045-A, and ADC-046-B. In certain embodiments, any one of the four disulfide bonds is broken under reducing conditions, two (2) reactive cysteine sulfhydryl moieties are produced. In further embodiments, each of the two reactive cystine sulfhydryl moieties is a point of attachment for a linker-drug, such that two (n = 2) linker-drugs may be attached to the reduced antibody. In certain embodiments, any two of the four disulfide bonds are broken under reducing conditions, four (4) reactive cysteine sulfhydryl moieties are produced. In further embodiments, each of the four reactive cystine sulfhydryl moieties is a point of attachment for a linker-drug, such that four (n = 4) linker-drugs may be attached to the reduced antibody. In certain embodiments, any three of the four disulfide bonds are broken under reducing conditions, six (6) reactive cysteine sulfhydryl moieties are produced. In further embodiments, each of the six reactive cystine sulfhydryl moieties is a point of 78 NAI-1539665006v1attachment for a linker-drug, such that six (n = 6) linker-drugs may be attached to the reduced antibody.

[0228] In some embodiments, the interchain disulfide bond is between two cysteine residues, and broken under reducing conditions, resulting in two reactive cysteine sulfhydryl moieties. In further embodiments, the interchain disulfide bridge in an AMHRII antibody is between a heavy chain and a light chain, such as between C220 of a heavy chain and C214 of a kappa light chain according to the EU numbering, or between C220 of a heavy chain according to the EU numbering and C214 of a lambda light chain according to the Kabat numbering. Additionally, or alternatively, the interchain disulfide bridge in an AMHRII antibody is between two heavy chains, such as between C226 and / or C229 of a first heavy chain and C226 and / or C229 of a second heavy chain according to the EU numbering. In some embodiments, the cysteine residues are in the hinge region of the AMHRII antibody. In some embodiments, the cysteine residue is at any one or more of positions 220, 226, or 229 in the heavy chain according to EU numbering (also referred to herein as C220, C226 or C229, respectively). In some embodiments, the cysteine residue is at position 214 in the light chain according to EU and / or Kabat numbering (also referred to herein as C214, such as position 214 in the kappa light chain according to EU and Kabat numbering or position 214 in the lambda light chain according to the Kabat numbering). In one embodiment, the cysteine residues are at each of positions 220, 226, and 229 in the heavy chain according to the EU numbering and position 214 in the light chain, according to EU or Kabat numbering. In one embodiment, the cysteine residues are at each of positions 220, 226, and 229 in the heavy chain according to the EU numbering and position 214 in the kappa light chain, according to EU and Kabat numbering. In one embodiment, the cysteine residues are at each of positions 220, 226, and 229 in the heavy chain according to the EU numbering and position 214 in the lambda light chain, according to Kabat numbering. In one embodiment, the cysteine residues are at any one or more of the following positions: (i) any one, or any two, or any three, or all four of positions 220, 226, and 229 in a first heavy chain according to the EU numbering; (ii) any one, or any two, or any three, or all four of positions 220, 226, and 229 in a second heavy chain according to the EU numbering; (iii) position 214 in a first light chain according to the Kabat numbering; and / or (iv) position 214 in a second light chain according to the Kabat numbering.

[0229] As used herein, C220, C226, and C229 refer to amino acid residues (cysteine, Cys, C) of an immunoglobulin identified according to the EU numbering. As it would be understood by one of skill in the art, such numberings accordingly represent amino acid residues of a 79 NAI-1539665006v1polypeptide aligned to those identified in an immunoglobulin, such as the one shown in www.imgt.org / IMGTScientificChart / Numbering / Hu_IGHGnber.html. For example, in some embodiments, C220 refers to the 103rdamino acid residue of SEQ ID NO:11, which is cysteine, C226 refers to the 109thamino acid residue of SEQ ID NO:11, which is cysteine, and C229 refers to the 112thamino acid residue of SEQ ID NO:11 which is also cysteine. In another embodiment, C220 refers to the 218thamino acid residue of SEQ ID NO:14, which is cysteine, C226 refers to the 224thamino acid residue of SEQ ID NO:14, which is cysteine, and C229 refers to the 227thamino acid residue of SEQ ID NO:14 which is also cysteine. In some embodiments, C214 refers to the 107thamino acid residue of SEQ ID NO:10, which is cysteine. In some embodiments, C214 refers to the 213thamino acid residue of SEQ ID NO:12 or 13, which is cysteine.

[0230] In certain embodiments, the AMHRII antibodies disclosed herein comprise four interchain disulfide bonds in the hinge region which may be reduced, thereby breaking the bond, and revealing a reactive sulfhydryl moiety that may be conjugated with a maleimide moiety on a linker-drug, such as the maleimide moiety on Linker-Drug (1) (or a salt thereof), Linker-Drug (1- A) (or a salt thereof), Linker-Drug (1-B) (or a salt thereof), Linker-Drug (2) (or a salt thereof), Linker-Drug (2-A) (or a salt thereof) or Linker-Drug (2-B) (or a salt thereof).

[0231] In one embodiment, the present disclosure provides a method of making an AMHRII- ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with a reducing agent; c) contacting the solution of b) with a solution comprising Linker-Drug (1) or a salt thereof:wherein the AMHRII-ADC is made. In some embodiments, the Linker-Drug (1) is Linker-Drug (1-A). In some embodiments, the Linker-Drug (1) is Linker-Drug (1-B). In some embodiments, the Linker-Drug (1) is a mixture of Linker-Drug (1-A) and Linker-Drug (1-B). 80 NAI-1539665006v1

[0232] In one embodiment, the present disclosure provides a method of making an AMHRII- ADC of Formula (II) or a salt thereof, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with a reducing agent; c) contacting the solution of b) with a solution comprising Linker-Drug (2) or a salt thereof:wherein the AMHRII-ADC is made. In some embodiments, the Linker-Drug (2) is Linker-Drug (2-A). In some embodiments, the Linker-Drug (2) is Linker-Drug (2- B). In some embodiments, the Linker-Drug (2) is a mixture of Linker-Drug (2-A) and Linker-Drug (2-B).

[0233] In one embodiment, the reducing agent is tris(2 carboxyethyl)phosphine (TCEP). AMHRII-ADCS

[0234] Any of the AMHRII antibodies described herein and any of the linker-drugs or salts thereof as described herein may be conjugated to generate an AMHRII-ADC. 81 NAI-1539665006v1

[0235] In one embodiment, the present disclosure provides an ADC of Formula (I):or a salt thereof, wherein: n is an integer from 1 to 8, and Ab represents an antibody that binds to AMHRII (“AMHRII antibody”). In some embodiments, the ADC is an (R)-epimer of Formula (I) or a salt thereof. Accordingly, the ADC is of Formula (I-A): 82 NAI-1539665006v1or a salt thereof. In some embodiments, the ADC is an (S)-epimer of Formula (I) or a salt thereof. Accordingly, the ADC is of Formula (I-B): 83 NAI-1539665006v1(I-B) or a salt thereof.

[0236] In some embodiments, the point of attachment to the Ab is through a cysteine or a lysine residue of the antibody. In some embodiments, the point of attachment to the Ab is through a lysine residue of the antibody. In one embodiment, the AMHRII-ADC comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In a further embodiment, the AMHRII antibody comprises two heavy chains, and accordingly n is 2, for example, ADC-027 and ADC-033. In another embodiment, the point of attachment to the Ab is from two cysteine residues which form an interchain disulfide bridge in an AMHRII antibody when not conjugated as the ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, for example, between two heavy chains (such as C226 and / or C229 accordingly to EU numbering) or between a heavy chain and a light chain (such as C220 of a heavy chain accordingly to EU numbering and C214 of a light chain according to EU and / or Kabat numbering). Accordingly, n is selected from the group consisting of 2, 4, 6 and 8. In some embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as 84 NAI-1539665006v1set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12 or 13. In a further embodiment, the AMHRII antibody comprises two heavy chains and two light chains, and accordingly n is 8, for example, ADC-028, ADC-303, and ADC-034.

[0237] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising: (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0238] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising: (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:4, 20, and 23; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:5, 21, and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs:6 and 22; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 19 and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:3.

[0239] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0240] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID 85 NAI-1539665006v1NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0241] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0242] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0243] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0244] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. 86 NAI-1539665006v1

[0245] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a VH comprising the amino acid sequence as set forth in SEQ ID NO:9.

[0246] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14.

[0247] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0248] In one embodiment, n is 1 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). In one embodiment, n is 2 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). In one embodiment, n is 3 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). In one embodiment, n is 4 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). In one embodiment, n is 5 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). In one embodiment, n is 6 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). In one embodiment, n is 7 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). In one embodiment, n is 8 in Formula (I) (or salt thereof), Formula (I-A) (or salt thereof), or Formula (I-B) (or salt thereof). 87 NAI-1539665006v1

[0249] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (A1):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted sulfurs are from cysteine residues (optionally selected from C220, C226, or C229 of a heavy chain of the AMHRII antibody according to the EU numbering, or C214 of a light chain of the AMHRII antibody according to the EU or Kabat numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof: 88 NAI-1539665006v1, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A1). In some embodiments, X is an (R)-epimer of the structure above or a salt thereof. Accordingly, X represents:89 NAI-1539665006v1or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A1). In some embodiments, X is an (S)-epimer of the structure above or a salt thereof. Accordingly, X represents:or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A1). 90 NAI-1539665006v1

[0250] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (B1):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue (optionally any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the AMHRII antibody according to the EU numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof: 91 NAI-1539665006v1, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B1). In some embodiments, X is an (R)-epimer of the structure above or a salt thereof. Accordingly, X represents:92 NAI-1539665006v1or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B1). In some embodiments, X is an (S)-epimer of the structure above or a salt thereof. Accordingly, X represents:or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B1).

[0251] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14. In one embodiment, the AMHRII antibody of Formula (A1) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12 or 13. In a further embodiment, the AMHRII antibody comprises two heavy chains and two light chains. In yet a further embodiment, the AMHRII antibody of Formula (A1) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:13. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced 93 NAI-1539665006v1in CHO cells, and accordingly, the AMRHII-ADC is ADC-034. In yet a further embodiment, the AMHRII antibody of Formula (A1) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMRHII-ADC is ADC-303. In one embodiment, the AMHRII antibody of Formula (B1) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In a further embodiment, the AMHRII antibody comprises two heavy chains. In one embodiment, the AMHRII antibody of Formula (B1) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMRHII-ADC is ADC-033. In one embodiment, the AMHRII antibody of Formula (B1) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells.

[0252] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises: (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0253] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises: (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:4, 20, and 23; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:5, 21, and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs:6 and 22; and (b) a VL 94 NAI-1539665006v1region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 19, and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:3.

[0254] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0255] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0256] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0257] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0258] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID 95 NAI-1539665006v1NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0259] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0260] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:9.

[0261] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14.

[0262] In one embodiment, the AMHRII antibody of Formula (A1) or (B1) comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0263] In one embodiment, the present disclosure provides an ADC of Formula (II):or a salt thereof, wherein: n is an integer from 1 to 8, and 96 NAI-1539665006v1Ab represents an antibody that binds to AMHRII (“AMHRII antibody”). In some embodiments, the ADC is an (R)-epimer of Formula (II) or a salt thereof. Accordingly, the ADC is of Formula (II-A):or a salt thereof. In some embodiments, the ADC is an (S)-epimer of Formula (II) or a salt thereof. Accordingly, the ADC is of Formula (II-B):(II-B) or a salt thereof.

[0264] In some embodiments, the point of attachment to the Ab is through a cysteine or a lysine residue of the antibody. In some embodiments, the point of attachment to the Ab is 97 NAI-1539665006v1through a lysine residue of the antibody. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In a further embodiment, the AMHRII antibody comprises two heavy chains and two light chains. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-031. In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof, comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-310-A. In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-311-B. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII- ADC is ADC-301. In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof, comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 98 NAI-1539665006v1(e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-043-A. In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-044-B. In a further embodiment, the AMHRII antibody comprises two heavy chains, and accordingly n is 2. In another embodiment, the point of attachment to the Ab is from two cysteine residues which form an interchain disulfide bridge in an AMHRII antibody when not conjugated as the ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, for example, between two heavy chains (such as C226 and / or C229 accordingly to EU numbering) or between a heavy chain and a light chain (such as C220 of a heavy chain accordingly to EU numbering and C214 of a light chain according to EU and / or Kabat numbering). Accordingly, n is selected from the group consisting of 2, 4, 6 and 8. In some embodiments, the AMHRII-ADC comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12 or 13. In a further embodiment, the AMHRII antibody comprises two heavy chains and two light chains, and accordingly n is 8. In one embodiment, the AMHRII- ADC of Formula (II) or a salt thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:13. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-032. In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:13. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC- 99 NAI-1539665006v1312-A. In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:13. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-313-B. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-302. In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:13. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-045-A. In one embodiment, the AMHRII- ADC of Formula (II-B) or a salt thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMHRII-ADC is ADC-046-B.

[0265] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising: (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8. 100 NAI-1539665006v1

[0266] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising: (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:4, 20, and 23. (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:5, 21, and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs:6 and 22; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 19, and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:3.

[0267] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising: a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0268] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0269] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3. 101 NAI-1539665006v1

[0270] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0271] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0272] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0273] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a VH comprising the amino acid sequence as set forth in SEQ ID NO:9.

[0274] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14.

[0275] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an AMHRII antibody comprising a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0276] In one embodiment, n is 1 in Formula (II) (or salt thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof). In one embodiment, n is 2 in Formula (II) (or salt 102 NAI-1539665006v1thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof). In one embodiment, n is 3 in Formula (II) (or salt thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof). In one embodiment, n is 4 in Formula (II) (or salt thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof). In one embodiment, n is 5 in Formula (II) (or salt thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof). In one embodiment, n is 6 in Formula (II) (or salt thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof). In one embodiment, n is 7 in Formula (II) (or salt thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof). In one embodiment, n is 8 in Formula (II) (or salt thereof), Formula (II-A) (or salt thereof), or Formula (II-B) (or salt thereof).

[0277] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (A2):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted sulfurs are from cysteine residues (optionally selected from C220, C226, or C229 of a heavy chain of the AMHRII antibody according to the EU numbering, or C214 of a light chain of the AMHRII antibody according to the EU or Kabat numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof: 103 NAI-1539665006v1wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A2). In some embodiments, X is an (R)-epimer of the structure above or a salt thereof. Accordingly, X represents:or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A2). In some embodiments, X is an (S)-epimer of the structure above or a salt thereof. Accordingly, X represents: 104 NAI-1539665006v1or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A2).

[0278] In another aspect, the present disclosure provides an antibody-drug conjugate (ADC) of Formula (B2):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue (optionally any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the 105 NAI-1539665006v1AMHRII antibody according to the EU numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B2). In some embodiments, X is an (R)-epimer of the structure above or a salt thereof. Accordingly, X represents:or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B2). In some embodiments, X is an (S)-epimer of the structure above or a salt thereof. Accordingly, X represents: 106 NAI-1539665006v1or a salt thereof, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B2).

[0279] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14. In one embodiment, the AMHRII antibody of Formula (A2) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12 or 13. In a further embodiment, the AMHRII antibody comprises two heavy chains and two light chains. In one embodiment, the AMHRII antibody of Formula (A2) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:13. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMRHII-ADC is ADC-032, ADC-312-A, or ADC-313-B. In one embodiment, the AMHRII antibody of Formula (A2) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the cysteine residues are the 218th, 224th, and 227thamino acid residues of SEQ ID NO:14 and the 213thamino acid residue of SEQ ID NO:12. In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO 107 NAI-1539665006v1cells, and accordingly, the AMRHII-ADC is ADC-302, ADC-045-A, or ADC-046-B.In one embodiment, the AMHRII antibody of Formula (B2) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In a further embodiment, the AMHRII antibody comprises two heavy chains. In one embodiment, the AMHRII antibody of Formula (B2) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMRHII-ADC is ADC-031, ADC-310-A, or ADC-311-B. In one embodiment, the AMHRII antibody of Formula (B2) comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). In further embodiments, the AMHRII antibody is not hypofucosylated, such as produced in CHO cells, and accordingly, the AMRHII-ADC is ADC-301, ADC-043-A, or ADC- 044-B.

[0280] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises: (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0281] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises: (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:4, 20, and 23; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:5, 21, and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs:6 and 22; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs:1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 19, and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:3. 108 NAI-1539665006v1

[0282] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0283] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0284] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0285] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0286] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a VH region comprising a VH CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:18, a VL 109 NAI-1539665006v1CDR2 comprising the amino acid sequence as set forth in SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence as set forth in SEQ ID NO:3.

[0287] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or a VL comprising the amino acid sequence as set forth in SEQ ID NO:8.

[0288] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:9.

[0289] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14.

[0290] In one embodiment, the AMHRII antibody of Formula (A2) or (B2) comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:13.

[0291] In one embodiment, the AMHRII-ADC is of the following Formula (C):or a salt thereof, wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue of the CH2 domain of the AMHRII antibody, such as K248. In some embodiments, the ADC is an (R)-epimer of Formula (C) or a salt thereof: 110 NAI-1539665006v1(C-A) In some embodiments, the ADC is an (S)-epimer of Formula (C), e.g., Formula (C-B), or a salt thereof:. (C-B) 111 NAI-1539665006v1

[0292] In one embodiment, the AMHRII-ADC is of the following Formula (D):or a salt thereof, wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue of the CH2 domain of the AMHRII antibody, such as K248. In some embodiments, the ADC is an (R)-epimer of Formula (D), e.g., Formula (D-A), or a salt thereof:(D-A) In some embodiments, the ADC is an (S)-epimer of Formula (D), e.g., Formula (D-B), or a salt thereof: 112 NAI-1539665006v1(D-B)

[0293] In some embodiments, the AMHRII antibody of Formula (C), Formula (C-A), Formula (C-B), Formula (D), Formula (D-A), or Formula (D-B) or a salt of each thereof comprises a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is K248 of the AMHRII antibody, e.g., the 131stamino acid residue of SEQ ID NO:11 or the 246thamino acid of SEQ ID NO:14.

[0294] Additionally, or alternatively, the AMHRII antibody of Formula (C), Formula (C-A), Formula (C-B), Formula (D), Formula (D-A), or Formula (D-B) or a salt of each thereof comprises an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is K246 of the AMHRII antibody, e.g., the 129thamino acid residue of SEQ ID NO:11 or the 244thamino acid of SEQ ID NO:14.

[0295] In some embodiments, the AMHRII-ADC is represented by Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, wherein Ab is AMHRII antibody comprising a light chain comprising one or more CDRs comprising an amino acid sequence identical or substantially identical to one or more of SEQ ID NOs:1-3 and a heavy chain comprising one or more CDRs comprising an amino acid sequence identical or substantially identical to one or more of SEQ ID NOs:4-6.

[0296] In some embodiments, the AMHRII-ADC is represented by Formula (I), Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or a salt thereof or Formula (II-B) or a salt thereof, wherein Ab is AMHRII antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. 113 NAI-1539665006v1

[0297] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, or Formula (I-B) or a salt thereof, comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to 9, wherein n is 8.

[0298] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof comprises Linker-Drug (1) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof comprises Linker-Drug (1) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0299] In one embodiment, the AMHRII-ADC of Formula (I-A) or a salt thereof comprises Linker-Drug (1-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-A) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I-A) or a salt thereof comprises Linker-Drug (1-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-A) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical 114 NAI-1539665006v1or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0300] In one embodiment, the AMHRII-ADC of Formula (I-B) or a salt thereof comprises Linker-Drug (1-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-B) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I-B) or a salt thereof comprises Linker-Drug (1-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-B) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0301] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2, such as ADC-033. In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to 9, wherein n is 8, such as ADC-034.

[0302] In one embodiment, the AMHRII-ADC of Formula (I-A) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (I-A) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or 115 NAI-1539665006v1substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to 9, wherein n is 8.

[0303] In one embodiment, the AMHRII-ADC of Formula (I-B) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (I-B) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to 9, wherein n is 8.

[0304] In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof comprises Linker-Drug (1) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2, such as ADC-033. In one embodiment, the AMHRII-ADC of Formula (I) or a salt thereof comprises Linker-Drug (1) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8, such as ADC-034.

[0305] In one embodiment, the AMHRII-ADC of Formula (I-A) or a salt thereof comprises Linker-Drug (1-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-A) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I-A) or a salt thereof comprises Linker-Drug (1-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-A) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence 116 NAI-1539665006v1identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0306] In one embodiment, the AMHRII-ADC of Formula (I-B) or a salt thereof comprises Linker-Drug (1-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-B) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I-B) or a salt thereof comprises Linker-Drug (1-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (I-B) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0307] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2, such as ADC-301. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 8, such as ADC-302.

[0308] In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2, such as ADC-043-A. In one embodiment, the AMHRII-ADC of 117 NAI-1539665006v1Formula (II-A) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 8, such as ADC-045-A.

[0309] In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2, such as ADC-044-B. In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 8, such as ADC-046-B.

[0310] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof comprises Linker-Drug (2) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof comprises Linker-Drug (2) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0311] In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof comprises Linker-Drug (2-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II- A) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2, such as ADC-043-A. In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof comprises Linker-Drug (2-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II-A) via one or more reduced disulfide bridges of each 118 NAI-1539665006v1chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8, such as ADC-045-A.

[0312] In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof comprises Linker-Drug (2-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II- B) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2, such as ADC-044-B. In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof comprises Linker-Drug (2-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II-B) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8, such as ADC-046-B.

[0313] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9, wherein n is 2, such as ADC-031, ADC-310-A, or ADC-311-B. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, comprises an antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to 9, wherein n is 8, such as ADC-032, ADC-312-A, or ADC-313-B. 119 NAI-1539665006v1

[0314] In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof comprises Linker-Drug (2) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2, such as ADC-031. In one embodiment, the AMHRII-ADC of Formula (II) or a salt thereof comprises Linker-Drug (2) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8, such as ADC-032.

[0315] In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof comprises Linker-Drug (2-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II- A) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2, such as ADC-310-A. In one embodiment, the AMHRII-ADC of Formula (II-A) or a salt thereof comprises Linker-Drug (2-A) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II-A) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8, such as ADC-312-A.

[0316] In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof comprises Linker-Drug (2-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II- 120 NAI-1539665006v1B) via the K248 residue of each heavy chain of the AMHRII antibody, wherein the AMHRII antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2, such as ADC-311-B. In one embodiment, the AMHRII-ADC of Formula (II-B) or a salt thereof comprises Linker-Drug (2-B) or salt thereof, which is conjugated to the AMHRII antibody of Formula (II-B) via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:8 and a VH comprising an amino acid identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8, such as ADC-313-B.

[0317] In some embodiments, the AMHRII-ADC is represented by Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, wherein Ab is an AMHRII antibody comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8. In some embodiments, the AMHRII-ADC is represented by Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, wherein Ab is an AMHRII antibody comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13. In some embodiments, a cysteine or lysine residue of the AMHRII antibody is modified as disclosed herein and conjugated to a linker-drug as disclosed herein.

[0318] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and two or more of Linker-Drug (1) or a salt or epimer thereof, conjugated thereto.

[0319] In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises an AMHRII antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises an AMHRII antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13, wherein n is 8. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises Linker-Drug (1) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (I) or salt or epimer thereof via the K248 residue of each 121 NAI-1539665006v1heavy chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises Linker-Drug (1) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (I) or salt or epimer thereof via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226, and C229 of two heavy antibody chains and C214 of two light chains. Accordingly, n is 2, 4, 6, or 8. In some embodiments, all of C220, C226 and C229 of both heavy antibody chains and both of C214 of both light chains are modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0320] In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14, wherein n is 8. In one embodiment, the AMHRII- ADC of Formula (I) or a salt or epimer thereof comprises Linker-Drug (1) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (I) or salt or epimer thereof via the K248 residue of each heavy chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises Linker-Drug (1) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (I) or salt or epimer thereof via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. 122 NAI-1539665006v1In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0321] In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises an AMHRII antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises an AMHRII antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9, wherein n is 8. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises Linker-Drug (1) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (I) or salt or epimer thereof via the K248 residue of each heavy chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (I) or a salt or epimer thereof comprises Linker- Drug (1) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (I) or salt or epimer thereof via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0322] In one embodiment, the AMHRII-ADC comprises an AMHRII antibody and two or more of Linker-Drug (2), or a salt or epimer thereof, conjugated thereto.

[0323] In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises an AMHRII antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises an AMHRII antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to 123 NAI-1539665006v1SEQ ID NO:12 or 13, wherein n is 8. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises Linker-Drug (2) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (II) or salt or epimer thereof via the K248 residue of each heavy chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises Linker-Drug (2) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (II) or salt or epimer thereof via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C220, C226, and C229 of two heavy antibody chains and C214 of two light chains. Accordingly, n is 2, 4, 6, or 8. In some embodiments, all of C220, C226 and C229 of both heavy antibody chains and both of C214 of both light chains are modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0324] In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises an AMHRII antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises an AMHRII antibody comprising a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9, wherein n is 8. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises Linker-Drug (2) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (II) or salt or epimer thereof via the K248 residue of each heavy chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises Linker- Drug (2) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (II) or salt or epimer thereof via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a VL comprising an amino acid sequence identical or substantially identical to SEQ ID NO:7 or 8 and a VH comprising an amino acid sequence identical or substantially identical to SEQ ID NO:9. In some embodiments, the one or more 124 NAI-1539665006v1disulfide bridges prior to the reduction are selected from those formed among C220, C226 and C229 of the two heavy antibody chains and C214 of the light antibody chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226, and C229 the heavy antibody chains and C214 of the light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein, and accordingly, n is 8.

[0325] In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14, wherein n is 2. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises an AMHRII antibody comprising a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14, wherein n is 8. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises Linker- Drug (2) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (II) or salt or epimer thereof via the K248 residue of each heavy chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14. Accordingly, n is 2. In one embodiment, the AMHRII-ADC of Formula (II) or a salt or epimer thereof comprises Linker- Drug (2) or salt or epimer thereof, which is conjugated to the AMHRII antibody of Formula (II) or salt or epimer thereof via one or more reduced disulfide bridges of each chain of the AMHRII antibody, wherein the antibody comprises a light chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:12 or 13 and a heavy chain comprising an amino acid sequence identical or substantially identical to SEQ ID NO:14. In some embodiments, the one or more disulfide bridges prior to the reduction are selected from those formed among C226 and C229 of two heavy antibody chains and C220 of each heavy chain and C214 of each light chain. Accordingly, n is 2, 4, 6, or 8. In some embodiments, each of C220, C226 and C229 of each heavy antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein and each C214 of each light antibody chain is modified to conjugated directly or indirectly to a linker-drug as disclosed herein and accordingly, n is 8.

[0326] AMHRII-ADCs as disclosed herein can have superior properties such as long retention time within the body, a high monomer ratio (low aggregation rate), high functional substance 125 NAI-1539665006v1releasability in human cells, high stability (for example in mouse plasma), and desirable cytotoxicity to target cells (such as AMHRII expressing or overexpressing cancer cells). COMPOSITIONS

[0327] In another embodiment, the present disclosure provides a composition of AMHRII- ADCs (“AMHRII-ADC composition”) as disclosed herein. An AMHRII-ADC composition may comprise a plurality of AMHRII-ADCs as disclosed herein, wherein each AMHRII-ADC in the composition independently comprises a linker-drug as shown in Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, wherein n is independently 1, 2, 3, 4, 5, 6, 7, or 8. In other words, each antibody molecule in the composition may be conjugated to 1, 2, 3, 4, 5, 6, 7 or 8 linker-drugs. Therefore, a composition may be characterized by a “drug-to-antibody” ratio (DAR) ranging from about 1 to about 8. Methods to determine DAR are well known to the skilled person and include methods using Reverse Phase Chromatography, or HPLC-MS.

[0328] For example, in any embodiment, an AMHRII-ADC composition may exhibit a DAR of about 1 to about 8 or any subrange there between, for example, about 1 to about 4, about 1 to about 3, about 1 to about 2, about 2 to about 4, about 2 to about 3, about 3 to about 4, about 3 to about 5, about 5 to about 7, about 7 to about 8, about 1.5 to about 2, about 1.8 to about 2, about 1.9 to about 2, about 3.5 to about 4, about 3.6 to about 4, about 3.7 to about 4, about 3.8 to about 4, about 3.9 to about 4, about 3.5 to about 3.9, about 3.6 to about 3.9, about 3.7 to about 3.9, about 3.8 to about 3.9, about 3.5 to about 3.8, about 3.6 to about 3.8, about 3.7 to about 3.8, about 3.5 to about 3.7, about 3.6 to about 3.7, or about 3.5 to about 3.6. In one embodiment, the DAR is about 1 to about 2. In one embodiment, the DAR is about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2. In one embodiment, the DAR is about 1.5 to about 2.5, or any subrange there between. In one embodiment, the DAR is about 7 to about 8, or any subrange there between.

[0329] In one embodiment, the DAR is about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, 126 NAI-1539665006v1about 7.8, about 7.9, or about 8.0. In some embodiments, the DAR is about 2, about 4, about 6, or about 8. In some embodiments, the DAR is about 2. In some embodiment, the DAR is about 8.

[0330] In some embodiments, the AMHRII-ADC composition comprises a plurality of AMHRII-ADCs wherein the linker-drug as disclosed herein is conjugated to the AMHRII antibody through one or more lysine residues of the antibody as disclosed herein, such as K246, K248, K288, K290, or K317. In some embodiments, the AMHRII-ADC composition exhibits a DAR of about 1.5 to about 2.5. In some embodiments, the AMHRII-ADC composition exhibits a DAR of 1.5 or greater, 1.6 or greater, 1.7 or greater, 1.8 or greater, or 1.9 or greater. Additionally, or alternatively, the composition exhibits a DAR of 2.5 or less, 2.4 or less, 2.3 or less, 2.2 or less, or 2.1 or less. In some embodiments, the AMHRII-ADC composition exhibits a DAR of 1.6 to 2.4, 1.7 to 2.3, 1.8 to 2.2, or 1.9 to 2.1. In some embodiments the AMHRII-ADC composition exhibits a DAR of about 1.9 to about 2.1.

[0331] In one embodiment, the AMHRII-ADC composition as disclosed herein exhibits a DAR of about 2, wherein the linker-drugs are conjugated to the AMHRII antibody via site specific conjugation, as described herein, to a lysine of the AMHRII antibody (e.g., K246, K248, K288, K290, or K317 in the CH2 domain of the heavy chain). In one embodiment, the AMHRII-ADC composition as disclosed herein may exhibit a DAR of about 8, wherein the linker-drugs are conjugated to reduced cysteine moieties of an interchain disulfide bridge, e.g., in the hinge region, of the AMHRII antibody.

[0332] In one embodiment, at least a portion of the plurality of AMHRII-ADCs in an AMHRII-ADC composition as disclosed herein comprise hypofucosylated AMHRII antibodies. In one embodiment, the plurality of AMHRII-ADCs in an AMHRII-ADC composition as disclosed herein does not comprise hypofucosylated AMHRII antibodies. ADMINISTRATION, PHARMACEUTICAL COMPOSITION, AND DOSAGE

[0333] In another aspect, the present disclosure provides a pharmaceutical composition comprising an AMHRII-ADC as disclosed herein and a pharmaceutically acceptable carrier. In another aspect, the present disclosure provides a pharmaceutical composition comprising a composition of AMHRII-ADCs as disclosed herein and a pharmaceutically acceptable carrier (“AMHRII-ADC pharmaceutical composition”). An AMHRII-ADC pharmaceutical composition may comprise a plurality of AMHRII-ADCs as disclosed herein, wherein each AMHRII-ADC in the pharmaceutical composition independently comprises a linker-drug as shown in Formula (I) or a salt thereof, Formula (I-A) or a salt thereof, Formula (I-B) or a salt thereof, Formula (II) or a salt thereof, Formula (II-A) or a salt thereof, or Formula (II-B) or a salt thereof, wherein n is independently 1, 2, 3, 4, 5, 6, 7, or 8. In other words, each antibody molecule in the AMHRII- 127 NAI-1539665006v1ADC pharmaceutical composition may be conjugated to 1, 2, 3, 4, 5, 6, 7, or 8 linker-drugs. Therefore, an AMHRII-ADC pharmaceutical composition may be characterized by a DAR ranging from about 1 to about 8. In one embodiment, at least a portion of the plurality of AMHRII-ADCs in an AMHRII-ADC pharmaceutical composition as disclosed herein comprise hypofucosylated AMHRII antibodies. In one embodiment, the plurality of AMHRII-ADCs in an AMHRII-ADC composition as disclosed herein does not comprise hypofucosylated AMHRII antibodies.

[0334] In one embodiment, the AMHRII-ADC pharmaceutical composition exhibits a DAR of about 2, wherein the plurality of AMHRII-ADCs comprise linker-drugs conjugated via site specific conjugation, as described herein, to one or more lysine residues of the AMHRII antibody (e.g., K246, K248, K288, K290, or K317 of the CH2 domain). In one embodiment, the AMHRII- ADC pharmaceutical composition may exhibit a DAR of about 8, wherein the plurality of AMHRII-ADCs comprise linker-drugs conjugated to one or more reduced cysteine moieties of an interchain disulfide bridge, e.g., in the hinge region, of an AMHRII antibody and / or between each light and heavy chain.

[0335] An AMHRII-ADC pharmaceutical composition of the disclosure may be administered to a subject in need thereof, by various routes, including, but not limited to, oral, intravenous, intra-arterial, subcutaneous, parenteral, intranasal, intramuscular, intracranial, intracardiac, intraventricular, intratracheal, buccal, rectal, intraperitoneal, intradermal, topical, transdermal, and intrathecal, or otherwise by implantation or inhalation. The subject compositions may be formulated into preparations in solid, semi-solid, liquid, or gaseous forms; including, but not limited to, tablets, capsules, powders, granules, ointments, solutions, suppositories, enemas, injections, inhalants, and aerosols. The appropriate pharmaceutical composition and route of administration may be selected according to the intended application and therapeutic regimen.

[0336] Suitable pharmaceutical compositions for enteral administration include hard or soft gelatin capsules, pills, tablets, including coated tablets, elixirs, suspensions, syrups or inhalations and controlled release forms thereof.

[0337] Pharmaceutical compositions suitable for parenteral administration (e.g., by injection), include aqueous or non-aqueous, isotonic, pyrogen-free, sterile liquids (e.g., solutions, suspensions), in which the active ingredient is dissolved, suspended, or otherwise provided (e.g., in a liposome or other microparticulate). Such liquids may additional contain other pharmaceutically acceptable ingredients, such as anti-oxidants, buffers, preservatives, stabilizers, bacteriostats, suspending agents, thickening agents, and solutes which render the pharmaceutical composition isotonic with the blood (or other relevant bodily fluid) of the intended recipient. 128 NAI-1539665006v1Examples of excipients include, for example, water, alcohols, polyols, glycerol, vegetable oils, and the like. Examples of suitable isotonic carriers for use in such compositions include sodium chloride injection, Ringer's Solution, or Lactated Ringer's Injection. Similarly, the particular dosage regimen, including dose, timing, and repetition, will depend on the particular individual and that individual's medical history, as well as empirical considerations such as pharmacokinetics (e.g., half-life, clearance rate, etc.).

[0338] In further embodiments, an AMHRII-ADC pharmaceutical composition comprises 20 mM Histidine. Additionally or alternatively, an AMHRII-ADC pharmaceutical composition comprises 5% trehalose. Additionally or alternatively, an AMHRII-ADC pharmaceutical composition has a pH of about 5 to about 6, such as 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0. In further embodiments, an AMHRII-ADC pharmaceutical composition comprises 20 mM histidine and 5% trehalose and has a pH of about 5 to about 6, such as 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0. In further embodiments, an AMHRII-ADC pharmaceutical composition comprises 20 mM histidine and 5% trehalose and has a pH of 6.0.

[0339] Frequency of administration may be determined and adjusted over the course of therapy and is based on reducing the number of proliferative or tumorigenic cells, maintaining the reduction of such neoplastic cells, reducing the proliferation of neoplastic cells, or delaying the development of metastasis. In some embodiments, the dosage administered may be adjusted or attenuated to manage potential side effects and / or toxicity. Alternatively, sustained continuous release compositions of a subject therapeutic composition may be appropriate.

[0340] It will be appreciated by one of skill in the art that appropriate dosages can vary from patient to patient. Determining the optimal dosage will generally involve the balancing of the level of therapeutic benefit against any risk or deleterious side effects. The selected dosage level will depend on a variety of factors including, but not limited to, the activity of the particular compound, the route of administration, the time of administration, the rate of excretion of the compound, the duration of the treatment, other drugs, compounds, and / or materials used in combination, the severity of the condition, and the species, sex, age, weight, condition, general health, and prior medical history of the patient. The amount of compound and route of administration will ultimately be at the discretion of the physician, veterinarian, or clinician, although generally the dosage will be selected to achieve local concentrations at the site of action that achieve the desired effect without causing substantial harmful or deleterious side-effects.

[0341] In general, an AMHRII-ADC of the disclosure may be administered in various ranges. These include about 5 μg / kg body weight to about 100 mg / kg body weight per dose; about 50 μg / kg body weight to about 5 mg / kg body weight per dose; about 100 μg / kg body weight to 129 NAI-1539665006v1about 10 mg / kg body weight per dose; and any values within the aforementioned ranges. Other ranges include about 100 μg / kg body weight to about 20 mg / kg body weight per dose and about 0.5 mg / kg body weight to about 20 mg / kg body weight per dose. In some embodiments, the dosage is at least about 100 μg / kg body weight, at least about 250 μg / kg body weight, at least about 750 μg / kg body weight, at least about 3 mg / kg body weight, at least about 5 mg / kg body weight, at least about 10 mg / kg body weight.

[0342] In any event, an antibody or antigen-binding portion thereof of the disclosure may be administered as needed to subjects (or a subject) in need thereof. Determination of the frequency of administration may be made by persons skilled in the art, such as an attending physician based on considerations of the condition being treated, age of the subject being treated, severity of the condition being treated, general state of health of the subject being treated and the like.

[0343] In some embodiments, the course of treatment involving an AMHRII-ADC of the present disclosure comprises multiple doses of the selected drug product over a period of weeks or months. For example, an AMHRII-ADC of the present disclosure may be administered once every day, every two days, every four days, every week, every ten days, every two weeks, every three weeks, every month, every six weeks, every two months, every ten weeks, or every three months. In this regard, it will be appreciated that the dosages may be altered or the interval may be adjusted based on patient response and clinical practices.

[0344] Dosages and regimens may also be determined empirically for the disclosed therapeutic compositions in individuals who have been given one or more administration(s). For example, individuals may be given incremental dosages of a therapeutic composition produced as described herein. In some embodiments, the dosage may be gradually increased, reduced, or attenuated based respectively on empirically determined or observed side effects or toxicity. To assess efficacy of the selected composition, a marker of the specific disease, disorder or condition can be followed as described previously. For cancer, these include direct measurements of tumor size via palpation or visual observation, indirect measurement of tumor size by x-ray or other imaging techniques; an improvement as assessed by direct tumor biopsy and microscopic examination of the tumor sample; the measurement of an indirect tumor marker (e.g., PSA for prostate cancer) or a tumorigenic antigen, a decrease in pain or paralysis; improved speech, vision, breathing or other disability associated with the tumor; increased appetite; or an increase in quality of life as measured by accepted tests or prolongation of survival. It will be apparent to one of skill in the art that the dosage will vary depending on the individual, the type of neoplastic condition, the stage of neoplastic condition, whether the neoplastic condition has begun to metastasize to other location in the individual, and the past and concurrent treatments being used. 130 NAI-1539665006v1

[0345] Compatible pharmaceutical compositions for parenteral administration (e.g., intravenous injection) may comprise a plurality of AMHRII-ADCs as disclosed herein at a concentration of about 10 μg / mL to about 100 mg / mL. In some embodiments, a pharmaceutical composition comprises a plurality of AMHRII-ADCs at a concentration of about 20 μg / mL, 40 μg / mL, 60 μg / mL, 80 μg / mL, 100 μg / mL, 200 μg / mL, 300, μg / mL, 400 μg / mL, 500 μg / mL, 600 μg / mL, 700 μg / mL, 800 μg / mL, 900 μg / mL, or 1 mg / mL. In some embodiments, a pharmaceutical composition comprises a plurality of AMHRII-ADCs at a concentration of about 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 8 mg / mL, 10 mg / mL, 12 mg / mL, 14 mg / mL, 16 mg / mL, 18 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 60 mg / mL, 70 mg / mL, 80 mg / mL, 90 mg / mL, or 100 mg / mL.

[0346] The term “pharmaceutically acceptable,” as used herein, means that the vehicle, diluent, excipient and / or salts thereof, are chemically and / or physically compatible with other ingredients in the composition, and physiologically compatible with the recipient.

[0347] As used herein, the term “a pharmaceutically acceptable carrier and / or excipient” refers to a carrier, stabilizer, and / or excipient pharmacologically and / or physiologically compatible with a subject and an active agent, which is well known in the art (see, e.g., Remington's Pharmaceutical Sciences. Edited by Gennaro AR, 19th ed. Pennsylvania: Mack Publishing Company, 1995), and includes, but is not limited to a pH adjuster, surfactant, adjuvant, or an ionic strength enhancer. For example, a pH adjuster includes, but is not limited to, phosphate buffer; a surfactant includes, but is not limited to, cationic, anionic, or non-ionic surfactant, e.g., Tween-80; an ionic strength enhancer includes, but is not limited to, sodium chloride. Carriers, excipients, or stabilizers are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the carrier is an aqueous pH buffered solution. Examples of carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (e.g., less than about 10 amino acid residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt- forming counterions such as sodium; and / or nonionic surfactants such as TWEEN™, polyethylene glycol (PEG), and PLURONICS™. The term “carrier” can also refer to a diluent, adjuvant (e.g., Freund’s adjuvant (complete or incomplete)), excipient, or vehicle with which the therapeutic is administered. Such carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, 131 NAI-1539665006v1mineral oil, sesame oil and the like. Water is an exemplary carrier when a composition (e.g., a pharmaceutical composition) is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable excipients (e.g., pharmaceutical excipients) include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. Compositions can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained-release compositions and the like. Oral compositions, including compositions, can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Examples of suitable carriers are described in Remington’s Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA. Compositions, including pharmaceutical compounds, may contain a prophylactically or therapeutically effective amount of a D3-binding agent (e.g., an anti-D3 antibody), for example, in isolated or purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the subject (e.g., patient). The pharmaceutical composition should suit the mode of administration.

[0348] As used herein, the term “adjuvant” refers to a non-specific immunopotentiator, which can enhance immune response to an antigen or change the type of immune response in an organism when it is delivered together with the antigen to the organism or is delivered to the organism in advance. There are a variety of adjuvants, including, but not limited to, aluminum adjuvants (for example, aluminum hydroxide), Freund’s adjuvants (for example, Freund’s complete adjuvant and Freund’s incomplete adjuvant), Corynebacterium parvum, lipopolysaccharide, cytokines, and the like. Freund's adjuvant is a commonly used adjuvant in animal experiments. Aluminum hydroxide adjuvant is also commonly used in clinical trials. METHODS OF TREATMENT

[0349] Any of the AMHRII-ADCs disclosed herein may be used for treating any disease associated with the expression of human AMHRII. In some embodiments, the AMHRII expression is at cell membrane, see, for example, WO2018 / 189379A1, WO2018 / 189381A1, and WO2018 / 219956A1, each of which is enclosed herein by reference in its entirety. In one embodiment, the AMHRII-ADC comprises a hypofucosylated AMHRII antibody. In one embodiment, the AMHRII-ADC comprises an AMHRII antibody that is not hypofucosylated. In one embodiment, the disease is cancer. In one embodiment, the cancer is a gynecological cancer. In one embodiment, the cancer is a non-gynecological cancer. Additionally, or alternatively, 132 NAI-1539665006v1cancer cells express or overexpresses AMHRII, for example, at the cell membrane. See, WO2018 / 189379A1, WO2018 / 189381A1, and WO2018 / 219956A1. In one embodiment, the cancer is prostate cancer, breast cancer and gynecologic cancers expressing AMHRII, such as ovarian cancer, in particular metastatic ovarian cancer, serous cancer, hypernephroma, endometrioid, colloidal epithelium, prostate cancer, germ cell cancer, endometrial cancer, mixed Müllerian malignant tumor of the uterus, leiomyosarcoma, or endometrial stromal sarcoma. In one embodiment, the cancer is colon cancer; lung cancer (such as NSCLC); hepatocellular carcinoma, testis cancer; pancreatic cancer, kidney cancer, breast cancer, thyroid cancer, gastric cancer, adrenal cancer, bladder cancer, and prostate cancer. In one embodiment, the cancer is NSCLC.

[0350] The AMHRII-ADCs disclosed herein may be used alone or in combination with any suitable agent. It is well known that therapeutic monoclonal antibodies can lead to the depletion of cells bearing the antigen specifically recognized by the antibody. This depletion can be mediated through at least three mechanisms: antibody mediated cellular cytotoxicity (ADCC), complement dependent lysis, and direct anti-tumor inhibition of tumor growth through signals given via the antigen targeted by the antibody. Therefore, in one embodiment, the method of treating the AMHRII-related diseases (e.g., cancer) in a subject in need thereof, the method further comprises administering a second therapeutic agent to the subject.

[0351] "Complement dependent cytotoxicity" or "CDC" refers to the lysis of a target cell in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system to antibodies which are bound to their cognate antigen. To assess complement activation, a CDC assay, e.g., as described in Gazzano- Santoro et al., 1997, J. Immunol. Methods, 202(2):163-171 may be performed.

[0352] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a form of cytotoxicity in which secreted antibodies bound onto Fc receptors (FcRs) present on certain cytotoxic cells (e.g., Natural Killer (NK) cells, neutrophils, and macrophages) enable these cytotoxic effector cells to bind specifically to an antigen-bearing target cell and subsequently kill the target cell. To assess ADCC activity of a molecule of interest, an in vitro ADCC assay, such as that described in US Patent No.5,500,362 or 5,821,337 may be performed.

[0353] In another aspect, the present disclosure provides a method for treating a cancer associated with the expression of AMHRII comprising administering a subject in need thereof with a therapeutically effective amount of an AMHRII-ADC as provided herein. The term "treating" or "treatment", as used herein, means reversing, alleviating, or slowing the progression of a cancer associated with AMHRII expression. Particularly, the AMHRII-ADC disclosed 133 NAI-1539665006v1herein are useful for the treatment of AMHRII expressing cancers (for example, cancers expressing AMHRII at the cancer cell membrane), such as prostate cancer, breast cancer and gynecologic cancers expressing AMHRII, such as ovarian cancer, in particular metastatic ovarian cancer, serous cancer, hypernephroma, endometrioid, colloidal epithelium, prostate cancer, germ cell cancer, endometrial cancer, mixed Müllerian malignant tumor of the uterus, leiomyosarcoma, or endometrial stromal sarcoma. As used herein, the terms "patient" or "patient in need thereof" or "subject" or "subject in need thereof" is intended for a human or non-human mammal affected cancer disease with the expression of AMHRII.

[0354] A "therapeutically effective amount" of an ADC an amount of the AMHRII-ADC sufficient to treat said cancers associated with the expression of AMHRII. It will be understood, however, that the total daily usage of the AMHRII-ADC and compositions thereof can be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific antibody employed; the specific composition employed, the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific antibody employed; the duration of the treatment; drugs used in combination or coincidental with the specific polypeptide employed; and like factors well known in the medical arts. AMHRII-ADC may be used in combination with any other therapeutic strategy for treating AMHRII-expressing cancers (for example, cancers expressing AMHRII at the cancer cell membrane), such as prostate cancer, breast cancer and gynecologic cancers expressing AMHRII, such as ovarian cancer, in particular metastatic ovarian cancer, serous cancer, hypernephroma, endometrioid, colloidal epithelium, prostate cancer, germ cell cancer, endometrial cancer, mixed Müllerian malignant tumor of the uterus, leiomyosarcoma, or endometrial stromal sarcoma (e.g., external radiotherapy, chemotherapy or cytokines).

[0355] The present disclosure contemplates various dosing regimens. For example, dosing regimens comprising the administration of AMHRII-ADCs disclosed herein include a) a single weekly ADC dose administered for a period of up to 2 or 3 months; or b) once-weekly AMHRII- ADC doses for up to 4 weeks every 6 months for a period of up to 2 years; or c) consecutive daily AMHRII-ADC doses for a period of up to 4 weeks; or d) two to seven AMHRII-ADC doses, administered once per day, for a period of about two weeks. Following any of these AMHRII-ADC dosing schedules, additional therapeutic agents (external radiotherapy, chemotherapy or cytokines can be administered to the subject. 134 NAI-1539665006v1

[0356] As used herein, the terms "patient" or "patient in need thereof" or "subject" or "subject in need thereof" is intended for a human or non-human mammal affected cancer disease with the expression of AMHRII, such as at the cell membrane.

[0357] A "therapeutically effective amount" of an AMHRII-ADC an amount of the AMHRII- ADC sufficient to treat said cancers associated with the expression of AMHRII (for example, cancers expressing AMHRII at the cancer cell membrane). It will be understood, however, that the total daily usage of the AMHRII-ADC and compositions thereof will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific antibody employed; the specific composition employed, the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific antibody employed; the duration of the treatment; drugs used in combination or coincidental with the specific polypeptide employed; and like factors well known in the medical arts. Combined Use with Chemotherapies

[0358] An AMHRII-ADC may be used in combination with chemotherapies, including, for example, an anti-cancer agent, a cytotoxic agent or chemotherapeutic agent.

[0359] The term “anti-cancer agent” or “anti-proliferative agent” means any agent that can be used to treat a cell proliferative disorder such as cancer, and includes, but is not limited to, cytotoxic agents, cytostatic agents, anti-angiogenic agents, debulking agents, chemotherapeutic agents, radiotherapy and radiotherapeutic agents, targeted anti-cancer agents, BRMs, therapeutic antibodies, cancer vaccines, cytokines, hormone therapies, radiation therapy and anti-metastatic agents and immunotherapeutic agents. It will be appreciated that, in some embodiments as discussed above, such anti-cancer agents may comprise conjugates and may be associated with an AMHRII-ADC as disclosed herein prior to administration. For example, in some embodiments selected anti-cancer agents is linked to the unpaired cysteines of the engineered antibodies to provide engineered conjugates (e.g., antibody-drug conjugates) as set forth herein. Accordingly, such engineered conjugates are expressly contemplated as being within the scope of the present disclosure. In some embodiments, the disclosed anti-cancer agents are given in combination with an AMHRII-ADC comprising a different therapeutic agent as set forth above.

[0360] As used herein the term “cytotoxic agent” means a substance that is toxic to the cells and decreases or inhibits the function of cells and / or causes destruction of cells. In some embodiments, the substance is a naturally occurring molecule derived from a living organism. Examples of cytotoxic agents include, but are not limited to, small molecule toxins or 135 NAI-1539665006v1enzymatically active toxins of bacteria (e.g., Diptheria toxin, Pseudomonas endotoxin and exotoxin, Staphylococcal enterotoxin A), fungal (e.g., α-sarcin, restrictocin), plants (e.g., abrin, ricin, modeccin, viscumin, pokeweed anti-viral protein, saporin, gelonin, momoridin, trichosanthin, barley toxin, Aleurites fordii proteins, dianthin proteins, Phytolacca mericana proteins (PAPI, PAPII, and PAP-S), Momordica charantia inhibitor, curcin, crotin, saponaria officinalis inhibitor, gelonin, mitegellin, restrictocin, phenomycin, neomycin, and the tricothecenes) or animals, (e.g., cytotoxic RNases, such as extracellular pancreatic RNases; DNase I, including fragments and / or variants thereof).

[0361] For the purposes of the present disclosure a “chemotherapeutic agent” comprises a chemical compound that non-specifically decreases or inhibits the growth, proliferation, and / or survival of cancer cells (e.g., cytotoxic, or cytostatic agents). Such chemical agents are often directed to intracellular processes necessary for cell growth or division, and are thus particularly effective against cancerous cells, which generally grow and divide rapidly. For example, vincristine depolymerizes microtubules, and thus inhibits cells from entering mitosis. In general, chemotherapeutic agents can include any chemical agent that inhibits, or is designed to inhibit, a cancerous cell or a cell likely to become cancerous or generate tumorigenic progeny (e.g., TIC). Such agents are often administered and are often effective in combination, e.g., in regimens such as CHOP or FOLFIRI.

[0362] Examples of anti-cancer agents that may be used in combination with AMHRII-ADCs of the present disclosure (either as a component of a site specific conjugate or in an unconjugated state) include, but are not limited to, alkylating agents, alkyl sulfonates, aziridines, ethylenimines and methylamelamines, acetogenins, a camptothecin, bryostatin, callystatin, CC-1065, cryptophycins, dolastatin, duocarmycin, eleutherobin, pancratistatin, a sarcodictyin, spongistatin, nitrogen mustards, antibiotics, enediyne antibiotics, dynemicin, bisphosphonates, esperamicin, chromoprotein enediyne antiobiotic chromophores, aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN®doxorubicin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites, erlotinib, vemurafenib, crizotinib,sorafenib, ibrutinib, enzalutamide, folic acid analogues, purine analogs, androgens, anti-adrenals, folic acid replenisher such as frolinic acid, aceglatone, aldophosphamide glycoside, aminolevulinic acid, eniluracil, amsacrine, bestrabucil, bisantrene, edatraxate, defofamine, demecolcine, diaziquone, elfornithine, elliptinium acetate, an epothilone, 136 NAI-1539665006v1etoglucid, gallium nitrate, hydroxyurea, lentinan, lonidainine, maytansinoids, mitoguazone, mitoxantrone, mopidanmol, nitraerine, pentostatin, phenamet, pirarubicin, losoxantrone, podophyllinic acid, 2- ethylhydrazide, procarbazine, PSK®polysaccharide complex (JHS Natural Products, Eugene, OR), razoxane; rhizoxin; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, chloranbucil; GEMZAR®gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs, vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE®vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (Camptosar, CPT-11), topoisomerase inhibitor RFS 2000; difluorometlhylornithine; retinoids; capecitabine; combretastatin; leucovorin; oxaliplatin; inhibitors of PKC-alpha, Raf, H-Ras, EGFR and VEGF-A that reduce cell proliferation and pharmaceutically acceptable salts, acids or derivatives of any of the above. Also included in this definition are anti-hormonal agents that act to regulate or inhibit hormone action on tumors such as anti-estrogens and selective estrogen receptor modulators, aromatase inhibitors that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands, and anti- androgens; as well as troxacitabine (a 1,3- dioxolane nucleoside cytosine analog); antisense oligonucleotides, ribozymes such as a VEGF expression inhibitor and a HER2 expression inhibitor; vaccines, PROLEUKIN®rIL-2; LURTOTECAN®topoisomerase 1 inhibitor; ABARELIX®rmRH; Vinorelbine and Esperamicins and pharmaceutically acceptable salts, acids or derivatives of any of the above. Combined Use with Radiotherapies

[0363] The present disclosure also provides for the use of a combination of an AMHRII-ADC with a radiotherapy (e.g., any mechanism for inducing DNA damage locally within tumor cells such as gamma-irradiation, X-rays, UV-irradiation, microwaves, electronic emissions and the like). Combination therapy using the directed delivery of radioisotopes to tumor cells is also contemplated, and the disclosed AMHRII-ADCs may be used in connection with a targeted anti- cancer agent or other targeting means. Typically, radiation therapy is administered in pulses over a period of time from about 1 to about 2 weeks. The radiation therapy may be administered to subjects having head and neck cancer for about 6 to 7 weeks. Optionally, the radiation therapy may be administered as a single dose or as multiple, sequential doses.

[0364] It is understood that modifications that do not substantially affect the activity of the various embodiments described herein are also provided within the definition of the subject 137 NAI-1539665006v1matter described herein. Accordingly, the following examples are intended to illustrate but not limit the present disclosure. SEQUENCE TABLE SUMMARY

[0365] Appended to the instant application is a sequence table comprising a number of amino acid sequences. The following Table 2 provides a summary of the included sequences, where the underlined sequences represent the CDRs. Table 2: Sequence Table138 NAI-1539665006v1EXAMPLES Example 1. Preparation of AMHRII Antibodies

[0366] The AMHRII antibodies described herein were prepared according to the protocols described in WO2011 / 141653A1 and WO2018 / 219956A1, incorporated by reference herein in their entireties, using, for example, CHO and YB2 / 0 cell lines to control fucosylation at the Fc domain. mAb303, mAb304, and mAb305, whose sequences are specified in Tables 1A, Table 1B, and Table 2, were produced. It is noted that mAb304 and mAb305 share the same amino acid sequences, and are different in their production cells, e.g., mAb304 was produced using CHO cells (accordingly considered herein as not hypofucosylated), while mAb305 was produced using YB2 / 0 cells (accordingly considered herein as hypofucosylated). These antibodies were used to make the AMHRII-ADCs described herein, and in the following examples. 139 NAI-1539665006v1Example 2. Synthesis of Linker-Drug (1)

[0367] Linker-Drug (1) was prepared according to the following procedures: Synthesis of Intermediate (2)

[0368] Ac-Glu(OtBu)-Val-Cit-OH (19.9 mg, 39.7 μmol) was dissolved in N,N- dimethylformamide (400 μL); 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate (18.1 mg, 47.6 μmol), and 2,4,6-trimethylpyridine (6.27 μL, 47.6 μmol) were added thereto; and the mixture was stirred at room temperature for 10 minutes. Next, methyl 4-aminomandelate (8.63 mg, 47.6 μmol) was added, and the mixture was stirred at room temperature for 21.5 hours, then purified via reverse-phase fractionating chromatography. The fraction containing the product was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain the alcohol (2) (28.5 mg, quant).1H NMR (400 MHz, DMSO-d6) δ9.95 (s, 1H), 8.07 (d, J = 7.4 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 5.92 (brs, 1H), 5.36 (brs, 2H), 5.01 (s, 1H), 4.34-4.29 (m, 1H), 4.26-4.20 (m, 1H), 4.14-4.10 (m, 1H), 3.53 (s, 3H), 3.00-2.83 (m, 2H), 2.18-2.13 (m, 2H), 1.94-1.89 (m, 2H), 1.84-1.23 (m, 17H), 0.79 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.8 Hz, 3H). MS (ESI) m / z: 665.30 [M+H]+

[0369] Ac-Glu(t-Bu)-Glu(t-Bu)-Val-Cit-OH (50.0 mg, 72.8 μmol) was dissolved in N,N- dimethylformamide (800 μL), 1-[bis (dimethylamino) methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxide hexafluorophosphate (33.2 mg, 87.4 μmol), and 2,4,6-trimethylpyridine (11.5 μL, 87.4 μmol) were added thereto, and the mixture was stirred at room temperature for 10 minutes. Next, methyl 4-aminomandelate (15.8 mg, 87.4 μmol) was added, and the mixture was stirred at room temperature for 16 hours, then purified via reverse-phase fractionating 140 NAI-1539665006v1chromatography. A product-containing fraction was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain the alcohol (12) (54.0 mg, 63.5 μmol).

[0370] 1H NMR (400 MHz, DMSO-d6) δ10.00 (s, 1H), 8.26-7.88 (m, 3H), 7.68-7.60 (m, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.00-5.97 (m, 1H), 5.43 (brs, 2H), 5.08 (s, 1H), 4.40-4.37 (m, 1H), 4.32-4.19 (m, 3H), 3.60 (s, 3H), 3.09-2.90 (m, 2H), 2.25-2.18 (m, 4H), 2.03- 1.53 (m,10H), 1.46-1.36 (m, 20H), 0.86 (d, J = 6.8 Hz, 3H), 0.82 (d, J = 6.8 Hz, 3H).

[0371] MS (ESI) m / z: 850.40 [M+H]+

[0372] Intermediate (2) (140 mg, 0.165 mmol) was dissolved in N,N-dimethylformamide (4 mL), and the mixture was stirred while being ice-cooled for five minutes, after which bis(4- nitrophenyl) carbonate (108 mg, 0.355 mmol) and N,N-diisopropylethylamine (100 μL, 0.574 mmol) were added thereto, and the mixture was stirred for 18 hours in a nitrogen atmosphere at room temperature. The organic solvent was removed via evaporator, after which a 1:1 solution of acetonitrile and water was added thereto, and the mixture was purified via reverse-phase fractionating chromatography. A product-containing fraction was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain Intermediate (43) (130 mg, 0.128 mmol). MS (ESI) m / z: 1015.6 [M+H]+141 NAI-1539665006v1

[0373] Intermediate (43) (85 mg, 0.084 mmol) was dissolved in N,N-dimethylformamide (2 mL), and 1-hydroxybenzotriazole (20 mg, 0.13 mmol) and commercially available monomethyl auristatin E (MMAE, 63 mg, 0.088 mmol) were added thereto at room temperature. Next, diisopropylethylamine (75 μL, 0.43 mmol) was added thereto, after which the mixture was stirred for 23 hours in a nitrogen atmosphere at room temperature. The organic solvent was removed via evaporator, after which a 1:1 solution of acetonitrile and water was added thereto, and the mixture was purified via reverse-phase fractionating chromatography. A product- containing fraction was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain Intermediate (44) (94 mg, 0.059 mmol). MS (ESI) m / z: 1593.6 [M+H]+142 NAI-1539665006v1

[0374] Intermediate (44) (94 mg, 0.059 mmol) was dissolved in tetrahydrofuran (5 mL) and water (2 mL), lithium hydroxide (1.0 M, 0.6 mL, 0.6 mmol) was added thereto while the mixture was being ice-cooled, and the mixture was stirred in that state for 1 hour. Hydrochloric acid was added to the reaction solution to adjust the pH to 5, after which a 1:1 mixture of acetonitrile and water was added thereto, and the mixture was purified via reverse-phase fractionating chromatography. A product-containing fraction was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain Intermediate (45) (77 mg, 0.049 mmol). MS (ESI) m / z: 1579.7 [M+H]+143 NAI-1539665006v1

[0375] Intermediate (45) (77 mg, 0.049 mmol) was dissolved in N,N-dimethylformamide (3 mL), then ice-cooled, and N,N-diisopropylethylamine (50 μL, 0.29 mmol) and 1H- benzotriazole-1-yloxytripyrrolidinophosphonium hexafluorophosphate (87 mg, 0.17 mmol) were added thereto. Next, N-(5-aminopentyl) maleimide hydrochloride (35 mg, 0.16 mmol) was added thereto, and the mixture was returned to room temperature and stirred for 20 hours. Once the reaction was finished, purification was performed via reverse-phase fractionating chromatography. A product-containing fraction was recovered, vacuum-concentrated to remove acetonitrile, then lyophilized to obtain Intermediate (46) (65 mg, 0.037 mmol). MS (ESI) m / z: 1744.7 [M+H]+144 NAI-1539665006v1

[0376] Acetonitrile (2 mL) and an 85 wt. % aqueous solution of phosphoric acid (1.00 mL, 14.6 mmol) were sequentially added to compound (46) (65 mg, 0.037 mmol), and the mixture was stirred at room temperature for 6 hours. Once the reaction was complete, water (2 mL) was added thereto, the reaction solution was purified via reverse-phase fractionating chromatography, and a product-containing fraction was recovered and vacuum-concentrated to remove acetonitrile, then lyophilized to obtain Linker-Drug (1) (49 mg, 0.030 mmol). MS (ESI) m / z: 1631.6 [M+H]+145 NAI-1539665006v1Example 3. Synthesis of Linker-Drug (2)

[0377] Intermediate (2) (140 mg, 0.165 mmol) prepared as described in Example 2 was dissolved in N,N-dimethylformamide (4 mL), and the mixture was stirred while being ice-cooled for five minutes, after which bis(4-nitrophenyl) carbonate (108 mg, 0.355 mmol) and N,N- diisopropylethylamine (100 μL, 0.574 mmol) were added thereto, and the mixture was stirred for 18 hours in a nitrogen atmosphere at room temperature. The organic solvent was removed via evaporator, after which a 1:1 solution of acetonitrile and water was added thereto, and the mixture was purified via reverse-phase fractionating chromatography. A product-containing fraction was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain compound 43 (130 mg, 0.128 mmol). MS (ESI) m / z: 1015.6 [M+H]+146 NAI-1539665006v1

[0378] Intermediate (43) (67 mg, 0.066 mmol) was dissolved in N,N-dimethylformamide (2 mL), and 1-hydroxybenzotriazole (17 mg, 0.11 mmol) and commercially available Exatecan mesylate (CAS: 169869-90-3, 35 mg, 0.066 mmol) were added thereto at room temperature. Next, diisopropylethylamine (50 μL, 0.29 mmol) was added thereto, after which the mixture was stirred for 4 hours in a nitrogen atmosphere at room temperature. The organic solvent was removed via evaporator, after which a 1:1 solution of acetonitrile and water was added thereto, and the mixture was purified via reverse-phase fractionating chromatography. A product- containing fraction was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain compound 48 (57 mg, 0.043 mmol). MS (ESI) m / z: 1311.7 [M+H]+

[0379] Intermediate (48) (57 mg, 0.043 mmol) was dissolved in tetrahydrofuran (3 mL) and water (1.5 mL), lithium hydroxide (1.0M, 0.5 mL, 0.5 mmol) was added thereto while the mixture was being ice-cooled, and the mixture was stirred in that state for 1 hour. Hydrochloric acid was added to the reaction solution to adjust pH to 5, after which a 1:1 mixture of acetonitrile 147 NAI-1539665006v1and water was added thereto, and the mixture was purified via reverse-phase fractionating chromatography. A product-containing fraction was recovered, vacuum-concentrated to remove acetonitrile, and lyophilized to obtain compound 49 (45 mg, 0.035 mmol). MS (ESI) m / z: 1297.6 [M+H]+

[0380] Intermediate (49) (45 mg, 0.035 mmol) was dissolved in N,N-dimethylformamide (3 mL), then ice-cooled, and N,N-diisopropylethylamine (30 μL, 0.17 mmol) and 1H- benzotriazole-1-yloxytripyrrolidinophosphonium hexafluorophosphate (55 mg, 0.11 mmol) were added thereto. Next, N-(5-aminopentyl) maleimide hydrochloride (22 mg, 0.10 mmol) was added thereto, and the mixture was returned to room temperature and stirred for 18 hours. Once the reaction was finished, purification was performed via reverse-phase fractionating chromatography. A product-containing fraction was recovered, vacuum-concentrated to remove 148 NAI-1539665006v1acetonitrile, and then lyophilized to obtain compound (50) (22 mg, 0.015 mmol). MS (ESI) m / z: 1462.7 [M+H]+

[0381] Acetonitrile (1 mL) and an 85 wt. % aqueous solution of phosphoric acid (1.0 mL, 14.6 mmol) were sequentially added to intermediate (50) (22 mg, 0.015 mmol), and the mixture was stirred at room temperature for 1.5 hours. Once the reaction was complete, water (1 mL) was added thereto, the reaction solution was purified via reverse-phase fractionating chromatography, and a product-containing fraction was recovered and vacuum-concentrated to remove acetonitrile, then lyophilized to obtain Linker-Drug (2) (18.8 mg, 0.0139 mmol).1H NMR (300 MHz; DMSO-d6) δ10.04 (s, 1H), 8.10-8.05 (m, 4H), 7.80-7.77 (m, 2H), 7.59-7.55 (m, 2H), 7.35- 7.30 (m, 3H), 6.99 (d, J = 8.8 Hz, 2H), 6.54-6.53 (m, 1H), 6.01 (brs, 1H), 5.74 (d, J = 9.0 Hz, 1H), 5.43 (brs, 4H), 5.33-5.28 (m, 2H), 4.29-4.15 (m, 4H), 3.19-2.98 (m, 5H), 2.43-2.38 (m, 5H), 149 NAI-1539665006v12.27-2.20 (m, 7H), 1.95-1.83 (m, 8H), 1.73-1.62 (m, 4H), 1.42-1.30 (m, 7H), 1.23-1.13 (m, 3H), 0.84 (m, 9H). MS (ESI) m / z: 1349.2 [M+H]+Example 4: Chromatographic Separation of Linker-Drug (1) Form A and Form B

[0382] Linker-Drug (1) is purified via reverse-phase fractionating chromatography on a C18 silica gel column (20 x 150 mm, 5 µm) by gradient conditions (mobile phase A: 0.1% TFA and 99.9% water, mobile phase B: 0.1% TFA and 99.9% MeCN). Each product-containing fractions (Linker-Drug (1) Form A, which is also referred to herein as Linker-Drug (1-A); and Linker- Drug (1) Form B, which is also referred to herein as Linker-Drug (1-B)) are recovered and vacuum-concentrated to remove acetonitrile, then are lyophilized to obtain Linker-Drug (1-A) and Linker-Drug (1-B) respectively.

[0383] RP-HPLC is further performed to analyze the produced Linker-Drugs. In brief, the analysis is conducted using an XBridge Shield RP 18, 4.6 x 150 mm, 3.5 µm (Waters catalog# 186003045), on an Agilent 1260 HPLC system. This system is equipped with a binary gradient pump, a temperature-controlled column compartment, an autosampler, and a diode array detector. The operational conditions are set as follows: a flow rate of 1.0 mL / min at 50 °C, with mobile phase A (MPA) comprising 0.1% trifluoroacetic acid (TFA) in water, and mobile phase B (MPB) containing 0.1% TFA in acetonitrile. Other elution conditions can be found in Table 3 below. UV at 215 nm, 252 nm, and 280 nm are used to detect the sample signals. 150 NAI-1539665006v1Example 5: Chromatographic Separation of Linker-Drug (2) (mixture) to Linker-Drug (2) Form A and Form B

[0384] Linker-Drug (2) (75 mg) was purified via reverse-phase fractionating chromatography on a C18 silica gel column (20 x 150 mm, 5 µm) by gradient conditions (mobile phase A: 0.1% TFA and 99.9% water, mobile phase B: 0.1% TFA and 99.9% MeCN). Each product-containing fractions (Linker-Drug (2) Form A, which is also referred to herein as Linker-Drug (2-A); and Linker-Drug (2) Form B, which is also referred to herein as Linker-Drug (2-B)) were recovered and vacuum-concentrated to remove acetonitrile, then lyophilized to obtain Linker-Drug (2-A) (40 mg) and Linker-Drug (2-B) (23 mg) respectively.

[0385] Linker-Drug (2-A): MS (ESI) m / Z: 1349.5 [M=H]+

[0386] Linker-Drug (2-B): MS (ESI) m / Z: 1349.5 [M=H]+

[0387] RP-HPLC was further performed to analyze the produced Linker-Drugs. In brief, the analysis was conducted using an XBridge Shield RP 18, 4.6 x 150 mm, 3.5 µm (Waters catalog# 151 NAI-1539665006v1186003045), on an Agilent 1260 HPLC system. This system was equipped with a binary gradient pump, a temperature-controlled column compartment, an autosampler, and a diode array detector. The operational conditions were set as follows: a flow rate of 1.0 mL / min at 50 °C, with mobile phase A (MPA) comprising 0.1% trifluoroacetic acid (TFA) in water, and mobile phase B (MPB) containing 0.1% TFA in acetonitrile. Other elution conditions can be found in Table 3 below. UV at 215 nm, 252 nm, and 280 nm was used to detect the sample signals.

[0388] Table 3. RP-HPLC Elution Conditions

[0389] An exemplary result is presented in FIG.1, showing the separation of the two linker- drug diastereomers overlayed on the diastereomeric mixture chromatogram. Example 6: Synthesis of Linker-Drug (2) Form B

[0390] Linker-Drug (2-B) (the (S) epimer) as illustrated in FIG.2 was also synthesized. Linker-Drug (2-B) is a synthetic derivative of Exatecan, a cytotoxic agent of the camptothecin family, containing a cleavable peptide linker (EEVC) and antibody conjugation site Maleimide- C5-amine which are attached to p-amino mandelic acid fragment. Linker-Drug (2-B) was synthesized (for example, as described herein in Example 3), using stereospecific intermediates. Linker-Drug (2-B) (0.54 g, 86 % yield) was obtained. MS (ESI, pos.): Calculated for C65H77FN12O19 [M+H]:1350.37, Found: 1350.30. NMR was further performed using the obtained Linker-Drug (2-B) (in DMSO) (data not shown). Example 7: Stochastic Conjugation through Reduction of Disulfides to make AMHRII- ADCs (see, e.g., Jackson, David, Organic Process Research & Development 2016, 20, 852-866, incorporated herein by reference in its entirety, and Tsuchikama, K. et al., Protein & Cell 2018, 9(1), 33-46, incorporated herein by reference in its entirety)

[0391] This example provides an exemplary protocol for reduction of the disulfides of the antibodies disclosed herein, and conjugation of the reduced antibodies to the linker-drug conjugates, e.g., Linker-Drugs (1), (1-A), (1-B), (2), (2-A), and (2-B), described herein. Step 1: Antibody Disulfide Reduction a) Dilute antibody to 15 mg / mL (0.1 mM IgG) in PBS (pH 7.4); 152 NAI-1539665006v1b) Prepare a fresh 20 mM (5.7 mg / mL) stock solution of tris(2 carboxyethyl)phosphine (TCEP) in H2O; c) Add 25 µL of TCEP stock solution to 1 mL of antibody from 1a (0.5 mM final concentration TCEP); d) Incubate at 37 °C for 2 hours (check for free thiols using 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) test); and e) Aliquot the reduced antibody into 4 tubes (250 µL each). Step 2: Linker-Drug Conjugation to Antibody a) Prepare a 10 mM stock solution of linker-cytotoxin conjugate in DMSO (DMA, DMF or CH3CN are also acceptable); b) Add 5 equivalents of 12.5 µL stock solution to each tube of reduced antibody (0.5 mM final concentration linker-cytotoxin conjugate stock solution); c) Incubate overnight at 4 °C for 4 hours at room temperature; check for free thiols using DTNB test; and d) Run analytical HIC to determine DAR and homogeneity. Example 8: Stochastic Conjugation through Reduction of Disulfides to make AMHRII- ADCs (see, e.g., Jackson, David, Organic Process Research & Development 2016, 20, 852-866, incorporated herein by reference in its entirety, and Tsuchikama,...

Claims

CLAIMS What is claimed is:or a salt thereof, wherein: n is an integer from 1 to 8, and Ab represents an antibody that binds to AMHRII (“AMHRII antibody”). 175 NAI-1539665006v12. The ADC of claim 1, wherein the ADC is of Formula (I-A):or a salt thereof. 176 NAI-1539665006v13. The ADC of claim 1, wherein the ADC is of Formula (I-B):or a salt thereof. 177 NAI-1539665006v14. An antibody-drug conjugate (ADC) of Formula (A1):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted sulfurs are from cysteine residues (optionally selected from C220, C226, or C229 of a heavy chain of the AMHRII antibody according to the EU numbering, or C214 of a light chain of the AMHRII antibody according to the EU or Kabat numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof: 178 NAI-1539665006v1, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A1).

5. An antibody-drug conjugate (ADC) of Formula (B1):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue (optionally any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the 179 NAI-1539665006v1AMHRII antibody according to the EU numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof:, wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B1).

6. The ADC of claim 5, wherein the AMHRII antibody comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:14, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering). 180 NAI-1539665006v17. The ADC of any one of claims 4-6, wherein the X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A1) or (B1). 181 NAI-1539665006v18. The ADC of any one of claims 4-6, wherein the X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A1) or (B1).

9. The ADC of any one of claims 1-8, wherein the AMHRII antibody comprises: (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:

8.

10. The ADC of any one of claims 1-9, wherein the AMHRII antibody comprises (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 20, and 23. (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 21, and 24; and 182 NAI-1539665006v1(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 6 and 22; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 19, and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:

3.

11. The ADC of any one of claims 1-10, wherein the AMHRII antibody comprises: (i) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (ii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iv) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL 183 NAI-1539665006v1CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (v) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

3.

12. The ADC of any one of claims 1-11, wherein the AMHRII antibody comprises a. a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or b. a VL comprising the amino acid sequence as set forth in SEQ ID NO:

8.

13. The ADC of any one of claims 1-12, wherein the AMHRII antibody comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:

9.

14. The ADC of any one of claims 1-13, wherein the AMHRII antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:

14.

15. The ADC of any one of claims 1-14, wherein the AMHRII antibody comprises a. a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or b. a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:

13.

16. The ADC of any one of claims 1-15, wherein the antibody is hypofucosylated, optionally wherein the antibody was produced in YB2 / 0 cells.

17. The ADC of any one of claims 1-15, wherein the antibody is not hypofucosylated, optionally wherein the antibody was produced in CHO cells.

18. The ADC of any one of claims 1-3 and 9-17, wherein n is 1.

19. The ADC of any one of claims 1-3 and 5-17, wherein n is 2. 184 NAI-1539665006v120. The ADC of any one of claims 1-3 and 9-17, wherein n is 3.

21. The ADC of any one of claims 1-3 and 9-17, wherein n is 4.

22. The ADC of any one of claims 1-3 and 9-17, wherein n is 5.

23. The ADC of any one of claims 1-3 and 9-17, wherein n is 6.

24. The ADC of any one of claims 1-3 and 9-17, wherein n is 7.

25. The ADC of any one of claims 1-4 and 7-17, wherein n is 8.

26. An antibody-drug conjugate (ADC) of Formula (II):or a salt thereof, wherein: n is an integer from 1 to 8, and Ab represents an antibody that binds to AMHRII (“AMHRII antibody”). 185 NAI-1539665006v127. The ADC of claim 26, wherein the ADC is of Formula (II-A)or a salt thereof.

28. The ADC of claim 26, wherein the ADC is of Formula (II-B)(II-B) or a salt thereof. 186 NAI-1539665006v129. An antibody-drug conjugate (ADC) of Formula (A2):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted sulfurs are from cysteine residues (optionally selected from C220, C226, or C229 of a heavy chain of the AMHRII antibody according to the EU numbering, or C214 of a light chain of the AMHRII antibody according to the EU or Kabat numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof:187 NAI-1539665006v1wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A2).

30. An antibody-drug conjugate (ADC) of Formula (B2):wherein each thick shaded line represents a chain of an antibody that binds to AMHRII (“AMHRII antibody”), the depicted CH2CH2CH2CH2NH moiety is from a lysine residue (optionally any one or more of K246, K248, K288, K290, or K317 of a heavy chain of the AMHRII antibody according to the EU numbering) of the AMHRII antibody, and X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (B2). 188 NAI-1539665006v131. The ADC of claim 30, wherein the AMHRII antibody comprises a light chain comprising an amino acid sequence as set forth in SEQ ID NO:12 or 13; and a heavy chain comprising an amino acid sequence as set forth in SEQ ID NO:11, wherein the lysine residue is the 246thamino acid residue of SEQ ID NO:14 (e.g., K248 according to the EU numbering).

32. The ADC of any one of claims 29-31, wherein X represents the structure below or a salt thereof:wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A2) or (B2).

33. The ADC of any one of claims 29-31, wherein X represents the structure below or a salt thereof:189 NAI-1539665006v1wherein the wavy line represents the point of attachment to the rest of the ADC of Formula (A2) or (B2).

34. The ADC of any one of claims 26-33, wherein the AMHRII antibody comprises: (i) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth SEQ ID NO:7; or (ii) a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:

8.

35. The ADC of any one of claims 26-34, wherein the AMHRII antibody comprises (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 20, and 23. (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 21, and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 6 and 22; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 and 18; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 19, and 25; and (3) a VL CDR3 having an amino acid sequence of SEQ ID NO:

3.

36. The ADC of any one of claims 26-35, wherein the AMHRII antibody comprises: (i) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or 190 NAI-1539665006v1(ii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iii) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (iv) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:20, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3; or (v) a VH region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:18, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

3.

37. The ADC of any one of claims 26-36, wherein the AMHRII antibody comprises a. a VL comprising the amino acid sequence as set forth in SEQ ID NO:7; or b. a VL comprising the amino acid sequence as set forth in SEQ ID NO:

8.

38. The ADC of any one of claims 26-37, wherein the AMHRII antibody comprises a VH comprising the amino acid sequence as set forth in SEQ ID NO:

9.

39. The ADC of any one of claims 26-38, wherein the AMHRII antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:

14. 191 NAI-1539665006v140. The ADC of any one of claims 26-39, wherein the AMHRII antibody comprises a. a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12; or b. a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:

13.

41. The ADC of any one of claims 26-40, wherein the antibody is hypofucosylated, optionally wherein the antibody was produced in YB2 / 0 cells.

42. The ADC of any one of claims 26-40, wherein the antibody is not hypofucosylated, optionally wherein the antibody was produced in CHO cells.

43. The ADC of any one of claims 26-28 and 34-42, wherein n is 1.

44. The ADC of any one of claims 26-28 and 30-42, wherein n is 2.

45. The ADC of any one of claims 26-28 and 34-42, wherein n is 3.

46. The ADC of any one of claims 26-28 and 34-42, wherein n is 4.

47. The ADC of any one of claims 26-28 and 34-42, wherein n is 5.

48. The ADC of any one of claims 26-28 and 34-42, wherein n is 6.

49. The ADC of any one of claims 26-28 and 34-42, wherein n is 7.

50. The ADC of any one of claims 26-29 and 32-42, wherein n is 8.

51. A composition of one or more of the ADCs of any one of claims 1-15, 17-40, and 42-50, wherein the AMHRII antibody is not hypofucosylated.

52. The composition of claim 51, wherein the AMHRII antibody comprises a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:7 or 8. 192 NAI-1539665006v153. The composition of claim 51 or 52, wherein the AMHRII antibody comprises a VL comprising the amino acid sequence as set forth in SEQ ID NO:

8.

54. The composition of claim 51 or 52, wherein the AMHRII antibody comprises a VL comprising the amino acid sequence as set forth in SEQ ID NO:

7.

55. The composition of claim 51 or 52, wherein the AMHRII antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:12 or 13.

56. The composition of any one of claims 51, 52, 53, or 55, wherein the AMHRII antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:

13.

57. The composition of any one of claims 51, 52, 54, or 55, wherein the AMHRII antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:

12.

58. A composition of one or more of the ADCs of any one of claims 1-16, 18-41, and 43-50, wherein the AMHRII antibody is hypofucosylated.

59. The composition of claim 58, wherein the AMHRII antibody comprises a VH CDR1, a VH CDR2, and a VH CDR3 in a VH comprising the amino acid sequence as set forth in SEQ ID NO:9 and a VL CDR1, a VL CDR2, and a VL CDR3 in a VL comprising the amino acid sequence as set forth in SEQ ID NO:

8.

60. The composition of claim 58 or 59, wherein the AMHRII antibody comprises a VL comprising the amino acid sequence as set forth in SEQ ID NO:

8.

61. The composition of any one of claims 58-60, wherein the AMHRII antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:14 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:

13. 193 NAI-1539665006v162. A pharmaceutical composition comprising one or more of the ADCs of any one of claims 1-50 or a composition of ADCs according to any one of claims 51-61 and a pharmaceutically acceptable carrier.

63. The pharmaceutical composition of claim 62, wherein the pharmaceutical composition is characterized by a drug-to-antibody ratio (“DAR”) of about 1 to about 8.

64. The pharmaceutical composition of claim 63, wherein the DAR is about 1 to about 2.

65. The pharmaceutical composition of claim 63 or 64, wherein the DAR is about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2.

66. The pharmaceutical composition of claim 63, wherein the DAR is about 2 to about 8.

67. The pharmaceutical composition of claim 63 or 66, wherein the DAR is about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8.

0.

68. A method of treating an AMHRII-related disease in a subject, comprising administering to the subject the ADC of any one of claims 1-50 or the composition of any one of claims 51-61 or the pharmaceutical composition of any one of claims 62-67 such that the AMHRII-related disease is treated in the subject.

69. The method of claim 68, wherein the disease is cancer, optionally cancer cells express AMHR2, further optionally cancer cells express AMHR2 at the cancer cell membrane.

70. The method of claim 69, wherein the cancer is a gynecological cancer.

71. The method of claim 69, wherein the cancer is selected from ovarian cancer, metastatic ovarian cancer, serous cancer, hypernephroma, endometrioid, colloidal epithelium, 194 NAI-1539665006v1prostate cancer, germ cell cancer, endometrial cancer, mixed Müllerian malignant tumor of the uterus, leiomyosarcoma, and endometrial stromal sarcoma.

72. The method of claim 69, wherein the cancer is selected from colon cancer; lung cancer; hepatocellular carcinoma, testis cancer; pancreatic cancer, kidney cancer, breast cancer, thyroid cancer, gastric cancer, adrenal cancer, bladder cancer, and prostate cancer.

73. The method of claim 69 or 72, wherein the cancer is a non-small cell lung cancer (NSCLC).

74. The method of any one of claims 68-73, wherein the method further comprises administering a second therapeutic agent to the subject, wherein the second therapeutic agent is an anti-cancer agent.

75. Use of the ADC of any one of claims 1-50 or the composition of any one of claims 51-61 or the pharmaceutical composition of any one of claims 62-67, in the manufacture of a medicament for treating an AMHRII-related disease.

76. The ADC of any one of claims 1-50 or the composition of any one of claims 51-61 or the pharmaceutical composition of any one of claims 62-67 for use in treating an AMHRII- related disease.

77. A method of making the ADC of any one of claims 1-25, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with a reducing agent; c) contacting the solution of b) with a solution comprising Linker-Drug (1):or salt thereof, wherein the ADC is made.

78. A method of making the ADC of any one of claims 26-50, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with a reducing agent; 195 NAI-1539665006v1c) contacting the solution of b) with a solution comprising Linker-Drug (2):or salt thereof, wherein the ADC is made.

79. The method of claim 77 or 78, wherein the reducing agent is tris(2 carboxyethyl)phosphine (TCEP).

80. A method of making the ADC of any one of claims 1-25, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with an affinity peptide conjugated to a thiophenol activation moiety; c) contacting the solution of b) with a solution comprising Linker-Drug (1):or salt thereof, wherein the ADC is made.

81. A method of making the ADC of any one of 26-50, comprising the steps of: a) providing a solution comprising the AMHRII antibody; b) contacting the solution of a) with an affinity peptide conjugated to a thiophenol activation moiety; c) contacting the solution of b) with a solution comprising Linker-Drug (2): 196 NAI-1539665006v1or salt thereof, wherein the ADC is made.

82. The method of claim 80 or 81, wherein the affinity peptide is a peptide of SEQ ID NO:

15.

83. The method of any one of claims 80-82, wherein the affinity peptide conjugated to a thiophenol activation moiety is:. 197 NAI-1539665006v184. The method of any one of claims 77, 79, 80, 82, and 83, wherein the Linker-Drug (1) is Linker-Drug (1-A):.

85. The method of any one of claims 77, 79, 80, 82, and 83, wherein the Linker-Drug (1) is Linker-Drug (1-B):. 198 NAI-1539665006v186. The method of any one of claims 78-79 and 81-83, wherein the Linker-Drug (2) is Linker-Drug (2-A):.

87. The method of any one of claims 78-79 and 81-83, wherein the Linker-Drug (2) is.

88. The method of any one of claims 77-87, wherein the method comprises an initial step of producing the AMHRII antibody in YB2 / 0 cells.

89. The method of any one of claims 77-87, wherein the method comprises an initial step of producing the AMHRII antibody in CHO cells. 199 NAI-1539665006v1

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