# US 2022/0033518 A1 · Prostate-specific membrane antigen antibody drug conjugates

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2022/0033518 A1
- Document ID: US20220033518A1
- Status: Published application
- Kind: A1
- Application number: 17/003,952
- Filed: 2020-08-26
- Published: 2022-02-03
- Earliest claimed: 2012-06-07
- Assignees: Ambrx, Inc.
- Applicants: Ambrx,Inc.
- Inventors: Richard Barnett; Feng Tian; Anna-Maria A. Hays Putnam; Marco Gymnopoulos; Nickolas Knudsen; Andrew Beck; Ying Sun
- Web page: https://patentgrep.com/patent/US20220033518A1

## CPC

- C07K 16/40: against enzymes
- A61K 47/6817: {Toxins}
- A61K 47/6869: {the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate}
- A61P 35/00: Antineoplastic agents
- C07K 5/0205: {containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof}
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to prostate-specific membrane antigen (PSMA) antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are αPSMA antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the αPSMA antibodies of the invention are conjugated to one or more toxins. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, dolastatin analogs, and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology uses.

## Claims

### Claim 1

A compound comprising Formula (VIII) or (IX):
wherein:
A is optional, and when present is lower alkylene, substituted lower alkylene, lower cycloalkylene, substituted lower cycloalkylene, lower alkenylene, substituted lower alkenylene, alkynylene, lower heteroalkylene, substituted heteroalkylene, lower heterocycloalkylene, substituted lower heterocycloalkylene, arylene, substituted arylene, heteroarylene, substituted heteroarylene, alkarylene, substituted alkarylene, aralkylene, or substituted aralkylene;
B is optional, and when present is a linker selected from the group consisting of lower alkylene, substituted lower alkylene, lower alkenylene, substituted lower alkenylene, lower heteroalkylene, substituted lower heteroalkylene, —O—, —O-(alkylene or substituted alkylene)-, —S—, —S-(alkylene or substituted alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene or substituted alkylene)-, —C(O)—, —C(O)-(alkylene or substituted alkylene)-, —C(S)—, —C(S)-(alkylene or substituted alkylene)-, —N(R′)—, —NR′-(alkylene or substituted alkylene)-, —C(O)N(R′)—, —CON(R′)-(alkylene or substituted alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene or substituted alkylene)-, —N(R′)CO-(alkylene or substituted alkylene)-, —N(R′)C(O)O—, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(S)N(R′)—, —N(R′)S(O)kN(R′)—, —N(R′)—N═, —C(R′)═N—, —C(R′)═N—N(R′)—, —C(R′)═N—N═, —C(R′)2—N═N—, and —C(R′)2—N(R′)—N(R′)—, where each R′ is independently H, alkyl, or substituted alkyl;
R is H, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl;
R1 is H, an amino protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R2 is OH, an ester protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R3 and R4 are each independently H, halogen, lower alkyl, or substituted lower alkyl, or R3 and R4 or two R3 groups optionally form a cycloalkyl or a heterocycloalkyl;
Z has the structure of:
R5 is H, COR8, C1-C6alkyl, or thiazole;
R8 is OH;
R6 is OH or H;
Ar is phenyl or pyridine;
R7 is C1-C6alkyl or hydrogen;
L is a linker selected from the group consisting of -alkylene-, -alkylene-C(O)—, -(alkylene-O)n-alkylene -, -(alkylene-O)n-alkylene-C(O)—, -(alkylene-O)n—(CH2)n′—NHC(O)—(CH2)n″—C(Me)2-S—S—(CH2)n″′, —NHC(O)-(alkylene-O)n″″-alkylene-, -(alkylene-O)n, alkylene-W—, -alkylene-C(O)—W—, -(alkylene-O)n-alkylene-U-alkylene-C(O)—, and -(alkylene-O)n-alkylene-U-alkylene-;
W has the structure of:
U has the structure of:
and
each n, n′, n″, n′″ and n″″ are independently integers greater than or equal to one;
or an active metabolite, or a pharmaceutically acceptable prodrug or solvate thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is a polypeptide.

### Claim 3 (depends on 2)

The compound of claim 2, wherein the polypeptide is an antibody.

### Claim 4 (depends on 3)

The compound of claim 3, wherein the antibody is an anti-prostate-specific membrane antigen (αPSMA) antibody.

### Claim 5 (depends on 4)

The compound of claim 4, wherein the αPSMA antibody comprises one or more non-naturally encoded amino acids.

### Claim 6 (depends on 4)

The compound of claim 4, wherein the αPSMA antibody comprises at least one and no more than ten non-naturally encoded amino acids.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R2 is a polypeptide.

### Claim 8 (depends on 7)

The compound of claim 7, wherein the polypeptide is an antibody.

### Claim 9 (depends on 8)

The compound of claim 8, wherein the antibody is an αPSMA antibody.

### Claim 10 (depends on 9)

The compound of claim 9, wherein the αPSMA antibody comprises one or more non-naturally encoded amino acids.

### Claim 11 (depends on 9)

The compound of claim 9, wherein the αPSMA antibody comprises at least one and no more than ten non-naturally encoded amino acids.

### Claim 12

The compound, or salt thereof, comprising Formula (X), (XI), (XII) or (XIII):
wherein:
A is optional, and when present is lower alkylene, substituted lower alkylene, lower cycloalkylene, substituted lower cycloalkylene, lower alkenylene, substituted lower alkenylene, alkynylene, lower heteroalkylene, substituted heteroalkylene, lower heterocycloalkylene, substituted lower heterocycloalkylene, arylene, substituted arylene, heteroarylene, substituted heteroarylene, alkarylene, substituted alkarylene, aralkylene, or substituted aralkylene;
B is optional, and when present is a linker selected from the group consisting of lower alkylene, substituted lower alkylene, lower alkenylene, substituted lower alkenylene, lower heteroalkylene, substituted lower heteroalkylene, —O—, —O-(alkylene or substituted alkylene)-, —S—, —S-(alkylene or substituted alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene or substituted alkylene)-, —C(O)—, —C(O)-(alkylene or substituted alkylene)-, —C(S)—, —C(S)-(alkylene or substituted alkylene)-, —N(R′)—, —NR′-(alkylene or substituted alkylene)-, —C(O)N(R′)—, —CON(R′)-(alkylene or substituted alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene or substituted alkylene)-, —N(R′)CO-(alkylene or substituted alkylene)-, —N(R′)C(O)O—, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(S)N(R′)—, —N(R′)S(O)kN(R′)—, —N(R′)—N═, —C(R′)═N—, —C(R′)═N—N(R′)—, —C(R′)═N—N═, —C(R′)2—N═N—, and —C(R′)2—N(R′)—N(R′)—, where each R′ is independently H, alkyl, or substituted alkyl;
R is H, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl;
R1 is H, an amino protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R2 is OH, an ester protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R3 and R4 are each independently H, halogen, lower alkyl, or substituted lower alkyl, or R3 and R4 or two R3 groups optionally form a cycloalkyl or a heterocycloalkyl;
Z has the structure of:
R5 is H, CO2H, C1-C6alkyl, or thiazole;
R6 is OH or H;
Ar is phenyl or pyridine;
R7 is C1-C6alkyl or hydrogen;
L1, L2, L3, and L4 are each linkers independently selected from the group consisting of a bond, -alkylene-, -(alkylene-O)n-alkylene-J-, -alkylene′-J-(alkylene-O)n-alkylene-, -J-(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-J-(alkylene-O)n′-alkylene-J′-, -(alkylene-O)n-alkylene-J-alkylene′-, —W—, -alkylene-W—, alkylene′-J-(alkylene-NMe)n-alkylene-W—, -J-(alkylene-NMe)n-alkylene-W—, -J-alkylene-NMe-alkylene′-NMe-alkylene″-W—, and -alkylene-J-alkylene′-NMe-alkylene″-NMe-alkylene″′-W—;
W has the structure of:
each J and J′ independently have the structure of:
and
each n and n′ are independently integers greater than or equal to one.

### Claim 13 (depends on 12)

The compound of claim 12, wherein R1 is a polypeptide.

### Claim 14 (depends on 13)

The compound of claim 13, wherein the polypeptide is an antibody.

### Claim 15 (depends on 14)

The compound of claim 14, wherein the antibody is an αPSMA antibody.

### Claim 16 (depends on 12)

The compound of claim 12, wherein R2 is a polypeptide.

### Claim 17 (depends on 16)

The compound of claim 16, wherein the polypeptide is an antibody.

### Claim 18 (depends on 17)

The compound of claim 17, wherein the antibody is an αPSMA antibody.

### Claim 19

A method for derivatizing a dolastatin analog comprising Formula (I), (III), (IV), (V), or (VI), the method comprising contacting the dolastatin analog with a reagent of Formula (XXXVII), wherein Formula (I), (III), (IV), (V), or (VI) correspond to:
wherein:
Z has the structure of:
R5 is H, COR8, C1-C6alkyl, or thiazole;
R8 is OH or —NH-(alkylene-O)n—NH2;
R6 is OH or H;
Ar is phenyl or pyridine;
R7 is C1-C6 alkyl or hydrogen;
Y is NH2—O— or methyl;
L, L1, L2, L3, and L4 are each linkers selected from the group consisting of a bond, -alkylene-, -alkylene-C(O)—, -(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-C(O)—, -(alkcylene-O)n—(CH2)n′—HC(O)—(CH2)n″—C(Me)2-S—S—(CH2)n″′—NHC(O)-(alkylene-O)n″″-alkylene-, -(alkylene-O)n-alkylene-W—, -alkylene-C(O)—W—, -(alkylene-O)n-alkylene-J-, -alkylene′-J-(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-J-alkylene′, J-(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-J-(alkylene-O)n′-alkylene-J′-, —W—, -alkylene-W—, alkylene′-J-(alkylene-NMe)n-alkylene-W—, and J-(alkylene-NMe)n-alkylene-W—, -(alkylene-O)n-alkylene-U-alkylene-C(O)-(alkylene-O)n-alkylene-U-alkylene-; -J-alkylene-NMe-alkylene′-NMe-alkylene″-W—, and -alkylene-J-alkylene′-NMe-alkylene″-NMe-alkylene″′-W—;
W has the structure of:
U has the structure of:
each J and J′ independently have the structure of:
or L is absent, Y is methyl, R5 is COR8, and R8 is —NH-(alkylene-O)n—NH2; and
each n, n′, n″, n″′ and n″″ are independently integers greater than or equal to one;
wherein Formula (XXXVII) corresponds to:
wherein:
A is optional, and when present is lower alkylene, substituted lower alkylene, lower alkenylene, substituted lower alkenylene, arylene, substituted arylene, heteroarylene, substituted heteroarylene, alkarylene, substituted alkarylene, aralkylene, or substituted aralkylene;
B is optional, and when present is a linker selected from the group consisting of lower alkylene, substituted lower alkylene, lower alkenylene, substituted lower alkenylene, —O—, —O-(alkylene or substituted alkylene)-, —S—, —S-(alkylene or substituted alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene or substituted alkylene)-, —C(O)—, —C(O)-(alkylene or substituted alkylene)-, —C(S)—, —C(S)-(alkylene or substituted alkylene)-, —N(R′)—, —NR′-(alkylene or substituted alkylene)-, —C(O)N(R′)—, —CON(R′)-(alkylene or substituted alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene or substituted alkylene)-, —N(R′)CO-(alkylene or substituted alkylene)-, —N(R′)C(O)O—, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(S)N(R′)—, —N(R′)S(O)kN(R′)—, —N(R′)—N═, —C(R′)═N—, —C(R′)═N—N(R′)—, —C(R′)═N—N═, —C(R′)2—N═N—, and —C(R′)2—N(R′)—N(R′)—, where each R′ is independently H, alkyl, or substituted alkyl;
each R′ is independently H, alkyl, or substituted alkyl;
K is
R is H, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl;
R1 is H, an amino protecting group, resin, at least one amino acid, or polynucleotide;
R2 is OH, an ester protecting group, resin, at least one amino acid, or polynucleotide; and
R3 and R4 are each independently H, halogen, lower alkyl, or substituted lower alkyl, or R3 and R4 or two R3 groups optionally form a cycloalkyl or a heterocycloalkyl.

### Claim 20 (depends on 19)

The method of claim 19, wherein the derivatized dolastatin analog comprises at least one oxime containing amino acid having the structure of Formula (VIII), (IX), (X), (XI), (XII), or (XIII):

### Claim 21 (depends on 19)

The method of claim 19, wherein the dolastatin analog is contacted with the reagent of Formula (XXXVII) in aqueous solution under mildly acidic conditions.

### Claim 22

A compound comprising Formula (XXV), (XXVI), (XXVII), (XXVIII), (XXIX), or (XXX):
wherein:
Z has the structure of:
R5 is H, CO2H, C1-C6alkyl, or thiazole;
R6 is OH or H;
Ar is phenyl or pyridine;
R1 is H, an amino protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R2 is OH, an ester protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R4 is H, halogen, lower alkyl, or substituted lower alkyl;
R7 is C1-C6alkyl or hydrogen;
L, L1, L2, L3, and L4 are each linkers selected from the group consisting of a bond, -alkylene-, -alkylene-C(O)—, -alkylene-J-, -(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-C(O)—, -(alkylene-O)n-J-, -(alkylene-O)n-J-alkylene-, -(alkylene-O)n—(CH2)n NHC(O)—(CH2)n″—C(Me)2-S—S—(CH2)n″′—NHC(O)-(alkylene-O)n″″-alkylene-, -(alkylene-O)i-alkylene-W—, -alkylene-C(O)—W—, -(alkylene-O)n-alkylene-J-, -alkylene′-J-(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-J-alkylene′, -J-(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-J-(alkylene-O)n′-alkylene-J′-, —W—, -alkylene-W—, alkylene′-J-(alkylene-NMe)n-alkylene-W—, -J-(alkylene-NMe)n-alkylene-W—, -(alkylene-O)n-alkylene-U-alkylene-C(O)—, -(alkylene-O)n-alkylene-U-alkylene-; -J-alkylene-NMe-alkylene′-NMe-alkylene″-W—, and -alkylene-J-alkylene′-NMe-alkylene″-NMe-alkylene″′-W—;
W has the structure of:
U has the structure of:
each J and J′ independently have the structure of:
each n and n′ are independently integers greater than or equal to one; and
each R16 is independently selected from the group consisting of hydrogen, halogen, alkyl, NO2, CN, and substituted alkyl.

### Claim 23 (depends on 22)

The compound of claim 22, wherein R1 is a polypeptide.

### Claim 24 (depends on 23)

The compound of claim 23, wherein the polypeptide is an antibody.

### Claim 25 (depends on 24)

The compound of claim 24, wherein the antibody is an αPSMA antibody.

### Claim 26 (depends on 22)

The compound of claim 22, wherein R2 is a polypeptide.

### Claim 27 (depends on 26)

The compound of claim 26, wherein the polypeptide is an antibody.

### Claim 28 (depends on 27)

The compound of claim 27, wherein the antibody is an αPSMA antibody.

### Claim 29

A compound comprising Formula (XXXI), (XXXII), (XXXIII), (XXXIV), (XXXV), or (XXXVI):
wherein:
Z has the structure of:
R5 is H, CO2H, C1-C6alkyl, or thiazole;
R6 is OH or H;
Ar is phenyl or pyridine;
R1 is H, an amino protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R2 is OH, an ester protecting group, resin, at least one amino acid, polypeptide, or polynucleotide;
R4 is H, halogen, lower alkyl, or substituted lower alkyl;
R7 is C1-C6alkyl or hydrogen;
L, L1, L2, L3, and L4 are each linkers selected from the group consisting of a bond, -alkylene-, -alkylene-C(O)—, -alkylene-J-, -(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-C(O)—, -(alkylene-O)n-J-, -(alkylene-O)n-J-alkylene-, -(alkylene-O)n—(CH2)n′—NHC(O)—(CH2)n″—C(Me)2-S—S—(CH2)n″′—NHC(O)-(alkylene-O)n″″-alkylene, -(alkylene-O)n-alkylene-W—, -alkylene-C(O)—W—, -(alkylene-O)n-alkylene-J-, -alkylene′-J-(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-J-alkylene′, -J-(alkylene-O)n-alkylene, -(alkylene-O)n-alkylene-J-(alkylene-O)n′-alkylene-J′-, —W—, -alkylene-W—, alkylene′-J-(alkylene-NMe)n-alkylene-W—, -J-(alkylene-NMe)n-alkylene-W—, -(alkylene-O)n-alkylene-U-alkylene-C(O)—, -(alkylene-O)n-alkylene-U-alkylene-; -J-alkylene-NMe-alkylene′-NMe-alkylene″-W—, and -alkylene -J-alkylene′-NMe-alkylene″-NMe-alkylene″′-W—;
U has the structure of:
each J and J independently have the structure of:
each n and n′ are independently integers greater than or equal to one;
D has the structure of:
each R17 is independently selected from the group consisting of H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, alkylalkoxy, substituted alkylalkoxy, polyalkylene oxide, substituted polyalkylene oxide, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkaryl, substituted alkaryl, aralkyl, substituted aralkyl, -(alkylene or substituted alkylene)-ON(R″)2, -(alkylene or substituted alkylene)-C(O)SR″, -(alkylene or substituted alkylene)-S—S-(aryl or substituted aryl), —C(O)R″, —C(O)2R″, or —C(O)N(R″)2, wherein each R″ is independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, alkaryl, substituted alkaryl, aralkyl, or substituted aralkyl;
each Z1 is a bond, CR17R17, O, S, NR′, CR17R17—CR17R17, CR17R17—O, O—CR17R17, CR17R17—S, S—CR17R17, CR17R17—NR′, or NR′—CR17R17;
each R′ is H, alkyl, or substituted alkyl;
each Z2 is selected from the group consisting of a bond, —C(O)—, —C(S)—, optionally substituted C1-C3 alkylene, optionally substituted C1-C3 alkenylene, and optionally substituted heteroalkyl;
each Z3 are independently selected from the group consisting of a bond, optionally substituted C1-C4 alkylene, optionally substituted C1-C4 alkenylene, optionally substituted heteroalkyl, —O—, —S—, —C(O)—, —C(S)—, and —N(R′)—;
each T3 is a bond, C(R″)(R″), O, or S; with the proviso that when T3 is O or S, R″ cannot be halogen;
each R″ is H, halogen, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl;
m and p are 0, 1, 2, or 3, provided that at least one of m or p is not 0;
M2 is
where (a) indicates bonding to the B group and (b) indicates bonding to respective positions within the heterocycle group;
M3 is
where (a) indicates bonding to the B group and (b) indicates bonding to respective positions within the heterocycle group;
M4 is
where (a) indicates bonding to the B group and (b) indicates bonding to respective positions within the heterocycle group;
each R19 is independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, ester, ether, thioether, aminoalkyl, halogen, alkyl ester, aryl ester, amide, aryl amide, alkyl halide, alkyl amine, alkyl sulfonic acid, alkyl nitro, thioester, sulfonyl ester, halosulfonyl, nitrile, alkyl nitrite, and nitro;
q is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11; and
each R16 is independently selected from the group consisting of hydrogen, halogen, alkyl, NO2, CN, and substituted alkyl.

### Claim 30 (depends on 29)

The compound of claim 29, wherein R1 is a polypeptide.

### Claim 31 (depends on 30)

The compound of claim 30, wherein the polypeptide is an antibody.

### Claim 32 (depends on 31)

The compound of claim 31, wherein the antibody is an PSMA antibody.

### Claim 33 (depends on 29)

The compound of claim 29, wherein R2 is a polypeptide.

### Claim 34 (depends on 33)

The compound of claim 33, wherein the polypeptide is an antibody.

### Claim 35 (depends on 34)

The compound of claim 34, wherein the antibody is an αPSMA antibody.

### Claim 36 (depends on 29)

The compound of claim 29, comprising Formula (XXXI-A):

### Claim 37 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36)

A pharmaceutical composition comprising a compound of any of claims 1-18 or 22-36 and a pharmaceutically acceptable carrier, excipient, or binder.