Conjugates of Anti-5t4 antibodies with drugs and uses thereof
Antibody-drug conjugates targeting the 5T4 antigen on tumor cells address the need for specific and potent cancer therapies by delivering cytotoxic payloads to enhance treatment efficacy.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- SOLVE THERAPEUTICS INC
- Filing Date
- 2025-11-18
- Publication Date
- 2026-05-28
AI Technical Summary
Current cancer treatments lack highly specific and potent therapies that can effectively target tumor cells expressing the 5T4 antigen and deliver sufficient cytotoxic drugs to these cells.
Development of antibody-drug conjugates that specifically bind to the 5T4 antigen, conjugating drug-linkers to anti-5T4 antibodies to release a cytotoxic payload, such as exatecan, to treat 5T4-positive cancers.
The antibody-drug conjugates provide targeted and potent treatment for 5T4-positive cancers by delivering cytotoxic drugs directly to tumor cells, enhancing treatment efficacy.
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Figure US2025055955_28052026_PF_FP_ABST
Abstract
Description
WSGR Docket No. 63125-725.601CONJUGATES AND USES THEREOF RELATED APPLICATIONS
[0001] This application claims the priority to and benefit of U. S. Provisional Application No. 63 / 723,077, filed November 20, 2024, the contents of which are incorporated herein by reference in their entirety.BACKGROUND
[0002] The tumor-associated antigen 5T4 is an attractive target for cancer immunotherapy.5T4 refers to the 5T4 oncofetal antigen. The novel anti-5 T4 antibody drug conjugates of the present invention provide highly specific and potent ADCs that bind to tumor cells expressing the 5T4 antigen and deliver sufficient cytotoxic drug to the cells, thus providing an innovative and effective treatment for cancer.SUMMARY OF THE INVENTION
[0003] The present disclosure provides antibody-drug conjugates that bind specifically to 5T4. Drug-linkers are conjugated to an anti-5T4 antibody or an antigen-binding portion thereof to form antibody-drug conjugates that target 5T4 and ultimately release a payload of choice (e.g., exatecan) to treat a 5T4-positive cancer.
[0004] In an aspect, the present disclosure provides a conjugate of the Formula (XX):IR40D Formula (XX)or a pharmaceutically acceptable salt thereof, wherein;L is a Targeting Unit;(K2-(S4)p)'n0R40is independently selected from hydrogen, Y, andD is selected from a Drug unit;n is selected from 0 and 1;WSGR Docket No. 63125-725.601m is selected from 0 and 1;wherein at least n or m is 1;p is selected from 0 and 1;z is selected from 0 and 1;X is selected from CH and N;Y is a -O-T1and -NH-T2;T1is a sugar cleavable unit;T2is peptide cleavable unit;S1is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-— S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3-C30 alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;54is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;WSGR Docket No. 63125-725.601wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;(ii) Ci-io alkyl, C2-10 alkenyl, C2.io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, C3.10 carbocycle and 3-to 10-membered heterocycle; and(iii) C3.10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6alkynyl;M2is a connector unit;K1is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;K2is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;each R20is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -N02, -NH2, -WSGR Docket No. 63125-725.601N(CI-6alkyl)2, Cuo alkyl, -C O haloalkyl, -O-C O alkyl, oxo, C3.12 carbocycle, and 3- to 12-membered heterocycle; andeach R30is independently selected from hydrogen; and Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci.10 alkyl, -Ci.10 haloalkyl, -O-C O alkyl, oxo, C3-12 carbocycle, and 3- to 12-membered heterocycle.
[0005] In some embodiments, for a conjugate or salt of Formula (XX), wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.
[0006] In an aspect, the present disclosure provides a conjugate of the Formula (A):D Formula (A)or a pharmaceutically acceptable salt thereof, wherein;L is a Targeting Unit;D is selected from a Drug unit;n is selected from 0 and 1;m is selected from 0 and 1;wherein at least n or m is 1;p is selected from 0 and 1;X is selected from CH and N;Y is a -O-T1and -NH-T2;T1is a sugar cleavable unit;T2is peptide cleavable unit;S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, -S(O)2-, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-,WSGR Docket No. 63125-725.601— S(0)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;54is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;(ii) Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and(iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6 alkynyl;M2is a connector unit;WSGR Docket No. 63125-725.601K1is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)--S(O)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;K2is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, -S(O)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;each R20is independently selected from hydrogen; and Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C3.i2carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.12 carbocycle, and 3- to 12-membered heterocycle; andeach R30is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, C O alkyl, -CMO haloalkyl, -O-Cuo alkyl, oxo, C3.12 carbocycle, and 3- to 12-membered heterocycle.
[0007] In some embodiments, for a conjugate or salt of Formula (A), when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines;
[0008] In an aspect, the present disclosure provides a conjugate of the Formula (Aa) or Formula (Ab):WSGR Docket No. 63125-725.601D Formula (Aa),0 Formula (Ab), oror a pharmaceutically acceptable salt thereof, wherein;L is a Targeting Unit;D is selected from a Drug unit;n is selected from 0 and 1;m is selected from 0 and 1;wherein at least n or m is 1;p is selected from 0 and 1;X is selected from CH and N;Y is a -O-T1and -NH-T2;T1is a sugar cleavable unit;T2is peptide cleavable unit;S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Ci0carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;S2is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -WSGR Docket No. 63125-725.601N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-, — S(0)—, — S(0)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3-C30 alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-— S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;54is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;(ii) Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and(iii) C3.10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6alkynyl;M2is a connector unit;K1is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -WSGR Docket No. 63125-725.601C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0- -S-, -S(0)--S(0)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;K2is selected from:(i) a peptide unit,(ii) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)--S(O)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;each R20is independently selected from hydrogen; and Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C3.i2carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci.10 alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.i2 carbocycle, and 3- to 12-membered heterocycle; andeach R30is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3.i2carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -O-CMO alkyl, oxo, C3.i2carbocycle, and 3- to 12-membered heterocycle.
[0009] In some embodiments, for a conjugate of Formula (Aa) or Formula (Ab) when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines;
[0010] In an aspect, the present disclosure provides a method of treating a subject with a disease or disorder comprising administering to a subject in need thereof a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), or Formula (A-4), or a pharmaceutical composition of any one thereof.INCORPORATION BY REFERENCE
[0011] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by referenceWSGR Docket No. 63125-725.601contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “figure” and “FIG.” herein), of which:
[0013] FIG. 1 shows in vivo antitumor activity of ADCs for 15 5T4 antibodies in the H226 xenograft model;
[0014] FIG. 2 shows in vivo antitumor activity of ADCs for 4 5T4 antibodies in the H520 NSCLC xenograft model;
[0015] FIG. 3 shows in vivo antitumor activity of ADCs for 8 5T4 antibodies in the H520 NSCLC xenograft model;
[0016] FIG. 4 shows in vivo antitumor activity of ADCs for 2 5T4 antibodies in the LCL-103H NSCLC xenograft model;
[0017] FIG. 5 displays in vivo antitumor activity of ADCs in the MDA-MB-468 xenograft model;
[0018] FIG. 6 shows in vivo antitumor activity of ADCs for 8 5T4 antibodies in the H520 NSCLC xenograft model;
[0019] FIG. 7 shows in vivo antitumor activity of ADCs in the Hep3B (liver) xenograft model;
[0020] FIG. 8 shows in vivo antitumor activity of ADC-40 in the LU5196 (NSCLC) xenograft model;
[0021] FIG. 9 in vivo antitumor activity of ADC-40 in the O VI 4661 (ovarian) xenograft model; and
[0022] FIG. 10 in vivo antitumor activity of ADCs in the H520 NSCLC xenograft model.DETAILED DESCRIPTION OF THE INVENTION
[0023] The following description sets forth numerous exemplary configurations, methods, parameters, and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure, but is instead provided as a description of exemplary embodiments.WSGR Docket No. 63125-725.601
[0024] In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments of the disclosure. However, one skilled in the art will understand that the disclosure may be practiced without these details.Definitions
[0025] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference.
[0026] " Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, and preferably having from one to fifteen carbon atoms (z.e., C1-C15 alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (z.e., C1-C13 alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (z.e., Ci-C8alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (z.e., C1-C5 alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (i.e., C1-C4 alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (z.e., Ci-C2 alkyl). In other embodiments, an alkyl comprises one carbon atom (z.e., Ci alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (z.e., C5-C15 alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (z.e., C5-C8alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (z.e., C2-C5alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (z.e., C3-C5 alkyl). In certain embodiments, the alkyl group is selected from methyl, ethyl, 1 -propyl (zz-propyl), 1 -methylethyl (z o-propyl), 1 -butyl (zz-butyl), 1 -methylpropyl ( ec-butyl), 2-methylpropyl (zso-butyl), 1, 1 -dimethylethyl (tert-butyl), 1 -pentyl (zz-pentyl). The alkyl is attached to the rest of the molecule by a single bond.
[0027] The term “Cx.y” or“Cx-Cy” when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain. For example, the term “Ci-ealkyl” refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched -chain alkyl groups that contain from 1 to 6 carbons. The term -Cx.yalkylene- refers to a substituted or unsubstituted alkylene chain with from x to y carbons in the alkylene chain. For example -Ci-ealkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.
[0028] " Alkoxy" refers to a radical bonded through an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above.WSGR Docket No. 63125-725.601
[0029] " Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon -carbon double bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12 alkenyl). In certain embodiments, an alkenyl comprises two to eight carbon atoms (z.e., C2-C8 alkenyl). In certain embodiments, an alkenyl comprises two to six carbon atoms (z.e., C2-C6alkenyl). In other embodiments, an alkenyl comprises two to four carbon atoms (z.e., C2-C4 alkenyl). The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (z.e., vinyl), prop-l-enyl (z.e., allyl), but-l-enyl, pent-l-enyl, penta- 1,4-dienyl, and the like.
[0030] " Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon -carbon triple bond, and preferably having from two to twelve carbon atoms (z.e., C2-Ci2alkynyl). In certain embodiments, an alkynyl comprises two to eight carbon atoms (z.e., C2-C8alkynyl). In other embodiments, an alkynyl comprises two to six carbon atoms (z.e., C2-C6 alkynyl). In other embodiments, an alkynyl comprises two to four carbon atoms (z.e., C2-C4alkynyl). The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.
[0031] The terms “Cx.yalkenyl” and “Cx.yalkynyl” refer to substituted or un substituted unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively. The term -Cx.yalkenylene- refers to a substituted or unsubstituted alkenylene chain with from x to y carbons in the alkenylene chain. For example, -C2-6alkenylene- may be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. An alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. The term -Cx.yalkynylene- refers to a substituted or un substituted alkynylene chain with from x to y carbons in the alkenylene chain. For example, -C2-6alkenylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. An alkynylene chain may have one triple bond or more than one triple bond in the alkynylene chain.
[0032] " Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and preferably having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, zz-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, anWSGR Docket No. 63125-725.601alkylene comprisesone to ten carbon atoms (i.e., Ci-C8alkylene). In certain embodiments, an alkylene comprisesone to eight carbon atoms (z.e., Ci-C8alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (z.e., C1-C5 alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (z.e., C1-C4 alkylene). In other embodiments, an alkylene comprisesone to three carbon atoms (z.e., C1-C3 alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (z.e., C1-C2 alkylene). In other embodiments, an alkylene comprises one carbon atom (z.e., Ci alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (z.e., C5-C8alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (z.e., C2-C5alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (z.e., C3-C5 alkylene).
[0033] " Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkenylene comprises two to ten carbon atoms (z.e., C2-Ci0alkenylene). In certain embodiments, an alkenylene comprises two to eight carbon atoms (z.e., C2-C8alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (z.e., C2-C5alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (z.e., C2-C4alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (z.e., C2-C3alkenylene). In other embodiments, an alkenylene comprises two carbon atom (z.e., C2alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (z.e., Cs-C8alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (z.e., C3-C5 alkenylene).
[0034] " Alkynylene" or "alkynylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carb on -carbon triple bond, and preferably having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkynylene comprises two to ten carbon atoms (z.e., C2-Ci0alkynylene). In certain embodiments, an alkynylene comprises two to eight carbon atoms (z.e., C2-C8alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (i.e., C2-C5alkynylene). In other embodiments, an alkynylene comprises twoWSGR Docket No. 63125-725.601to four carbon atoms (i.e., C2-C4alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (i.e., C2-C3alkynylene). In other embodiments, an alkynylene comprises two carbon atom i.e., C2alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (i.e., Cs-Cs alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (i.e., C3-C5alkynylene).
[0035] " Aryl" refers to a radical derived from an aromatic monocyclic or aromatic multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic multicyclic hydrocarbon ring system contains only hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) 71-electron system in accordance with the Hiickel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene.
[0036] " Aralkyl" refers to a radical of the formula -Rc-aryl where Rcis an alkylene chain as defined above, for example, methylene, ethylene, and the like.
[0037] " Aralkenyl" refers to a radical of the formula -Rd-aryl where Rdis an alkenylene chain as defined above. " Aralkynyl" refers to a radical of the formula -Re-aryl, where Reis an alkynylene chain as defined above.
[0038] Activated C-C group” refers to a cyclic alkyne which is highly reactive due to ring strain towards azide group to form a triazole.
[0039] Activated disulfide group” refers to a disulfide which is capable to react with a thiol to form a new disulfide bond.
[0040] “Carbocycle” refers to a saturated, unsaturated or aromatic rings in which each atom of the ring is carbon. Carbocycle may include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, are included in the definition of carbocyclic. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Bicyclic carbocycles maybe fused, bridged or spiro-ring systems. In some cases, spiro-ring carbocycles have at least two molecular rings with only one common atom.
[0041] “Carbocyclene” refers to a divalent carbocycle linking the rest of the molecule to a radical group.WSGR Docket No. 63125-725.601
[0042] The term “unsaturated carbocycle” refers to carbocycles with at least one degree of unsaturation and excluding aromatic carbocycles. Examples of unsaturated carbocycles include cyclohexadiene, cyclohexene, and cyclopentene.
[0043] " Cycloalkyl" refers to a fully saturated monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, and preferably having from three to twelve carbon atoms. In certain embodiments, a cycloalkyl comprises three to ten carbon atoms. In other embodiments, a cycloalkyl comprises five to seven carbon atoms. The cycloalkyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbomyl (z.e., bicyclo[2.2. l]heptanyl), norbornenyl, decalinyl,7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like.
[0044] " Cycloalkenyl" refers to an unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, preferably having from three to twelve carbon atoms and comprising at least one double bond. In certain embodiments, a cycloalkenyl comprises three to ten carbon atoms. In other embodiments, a cycloalkenyl comprises five to seven carbon atoms. The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls includes, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.
[0045] " Cycloalkylalkyl" refers to a radical of the formula -Rc-cycloalkyl where Rcis an alkylene chain as described above.
[0046] " Cycloalkylalkoxy" refers to a radical bonded through an oxygen atom of the formula -O-Rc-cycloalkyl where Rcis an alkylene chain as described above.
[0047] " Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro and iodo substituents.
[0048] As used herein, the term "haloalkyl" or “haloalkane” refers to an alkyl radical, as defined above, that is substituted by one or more halogen radicals, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1 -fluoromethyl-2 -fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally further substituted. Examples of halogen substituted alkanes (“haloalkanes”) include halomethane (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di-and trihalomethane (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1 -haloethane, 2-haloethane, 1,2-dihaloethane, 1 -halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combinationsWSGR Docket No. 63125-725.601of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, I, etc.). When an alkyl group is substituted with more than one halogen radicals, each halogen may be independently selected e.g., 1 -chloro, 2-fluoroethane.
[0049] " Fluoroalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more fluoro radicals, for example, trifluoromethyl, difluoromethyl, fluoromethyl,2,2,2-trifluoroethyl, 1 -fluoromethyl-2 -fluoroethyl, and the like.
[0050] " Aminoalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more amine radicals, for example, propan-2-amine, butane- 1,2-diamine, pentane-l,2,4-triamine and the like.
[0051] " Hydroxy alkyl" refers to an alkyl radical, as defined above, thatis substituted by one or more hydroxy radicals, for example, propan-l-ol, butane- 1,4-diol, pentane-l,2,4-triol, and the like.
[0052] " Alkoxyalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more alkoxy radicals, for example, methoxymethane, 1,3 -dimethoxybutane, 1-methoxypropane, 2-ethoxypentane, and the like.
[0053] " Cyanoalkyl" as used herein refers to an alkyl radical, as defined above, that is substituted by one or more cyano radicals, for example, acetonitrile, 2-ethyl-3-methylsuccinonitrile, butyronitrile, and the like.
[0054] “Heterocycle” refers to a saturated or unsaturated or aromatic ring comprising one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3 -to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. Bicyclic heterocycles may be fused, bridged or spiro -ring systems. In some cases, spiro-ring heterocycles have at least two molecular rings with only one common atom. The spiro-ring heterocycle includes at least one heteroatom.
[0055] “Heterocyclene” refers to a divalent heterocycle linking the rest of the molecule to a radical group.
[0056] " Heteroaryl" or “aromatic heterocycle” refers to a radical derived from a heteroaromatic ring radical that comprises one to eleven carbon atoms and at least one heteroatom wherein each heteroatom may be selected from N, O, and S. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems rings wherein at least one of the rings in the ring system is aromatic, ie., it contains a cyclic, delocalized (4n+2) ^-electron system in accordance with the Hiickel theory. The heteroatom(s) in the heteroaryl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl maybe attached to the rest of the molecule through anyWSGR Docket No. 63125-725.601atom of the heteroaryl, valence permitting, such as a carbon or nitrogen atom of the heteroaryl. Examples of heteroaryls include, but are not limited to, pyridine, pyrimidine, oxazole, furan, pyran, thiophene, isoxazole, benzimidazole, benzthiazole, and imidazopyridine.
[0057] An “X-membered heteroaryl” refers to the number of endocylic atoms, i.e., X, in the ring. For example, a 5 -membered heteroaryl ring or 5 -membered aromatic heterocycle has 5 endocyclic atoms, e.g., triazole, oxazole, thiophene, etc.
[0058] The term “unsaturated heterocycle” refers to heterocycles with at least one degree of unsaturation and excluding aromatic heterocycles. Examples of unsaturated heterocycles include dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydro pyridine. Heterocycles may be optionally substituted by one or more substituents such as those substituents described herein.
[0059] The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons or substitutable heteroatoms, e.g., NH, of the structure. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon with an oxo, imino or thioxo group.
[0060] As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. In some embodiments, substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=0), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-0H), hydrazino (=N- NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2), and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, and heterocycle, any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalky 1, haloalkenyl, haloalkynyl, oxo (=0),WSGR Docket No. 63125-725.601thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); wherein each Rais independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=0), thioxo (=S), cyano (-CN), nitro (-N02), imino (=N-H), oximo (=N-0H), hydrazine (=N- NH2), -Rb-0Ra, -Rb-0C(0)-Ra, -Rb-0C(0)-0Ra, -Rb-0C(0)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(0)Ra, -Rb-C(0)0Ra, -Rb-C(0)N(Ra)2, -Rb-0-Rc-C(0)N(Ra)2, -Rb-N(Ra)C(0)0Ra, -Rb-N(Ra)C(0)Ra, -Rb-N(Ra)S(0)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(0)tN(Ra)2(where t is 1 or 2); and wherein each Rbis independently selected from a direct bond or a straight or branched alkylene, alkenylene, oralkynylene chain, and each Rcis a straight or branched alkylene, alkenylene or alkynylene chain.
[0061] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.
[0062] The term “salt” or “pharmaceutically acceptable salt” refers to salts derived from a variety of organic and inorganic counter ions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, / ?-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salt is chosen from ammonium, potassium, sodium, calcium, and magnesium salts.WSGR Docket No. 63125-725.601
[0063] The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracap sular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, sub capsular, subarachnoid, intraspinal and intrasternal injection and infusion.
[0064] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.
[0065] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15)alginic acid; (16) pyrogen -free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.
[0066] In certain embodiments, the term “prevent” or “preventing” as related to a disease or disorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in the treated sample relative to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample.
[0067] The terms “treat,” “treating” or “treatment,” as used herein, may include alleviating, abating or ameliorating a disease or condition symptoms, preventing additional symptoms, ameliorating or preventing the underlying causes of symptoms, inhibiting the disease orWSGR Docket No. 63125-725.601condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and / or therapeutically.
[0068] The term "ligand" generally refers to a macromolecular compound capable of recognizing and binding to an antigen or receptor associated with a target cell. The ligand can be used to bring the drug to the target cell population that binds to the ligand, including but not limited to protein hormones, lectins, growth factors, antibodies, or others that can bind to cells, receptors and / or antigens molecule. The ligand can be an antibody. The ligand can be an antigen binding fragment.
[0069] The term “targeting moiety” or “Targeting Unit” refers to a structure that has a selective affinity for a target molecule relative to other non-target molecules. The targeting moiety binds to a target molecule. A Targeting Unit may include, for example, an antibody, a peptide, a ligand, a receptor, or a binding portion thereof. The target biological molecule may be a biological receptor or other structure of a cell such as a tumor antigen.
[0070] The term “antibody” means whole antibodies and any antigen binding fragment (i.e., “antigen-binding portion”) or single chain variants thereof. A whole antibody is a protein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (VH) and a heavy chain constant region comprising three domains, CHI, CH2 and CH3. Each light chain comprises a light chain variable region (VL or Vk) and a light chain constant region comprising one single domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with more conserved framework regions (FRs). Each VH and VL comprises three CDRs (HCDR herein designates a CDR from the heavy chain; and LCDR herein designates a CDR from the light chain) and four FRs, arranged from amino- to carb oxy -terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions contain a binding domain that interacts with an antigen. The constant regions may mediate the binding of the antibody to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. The assignment of amino acid numbers, and of FR and CDR regions, in the heavy or light chain may be in accordance with IMGT® definitions (Lefranc et al., Dev Comp Immunol. (2003) 27(l):55-77); or the definitions of Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, MD (1987 and 1991)); Chothia & Lesk, J Mol Biol. (1987) 196:901-17; Chothia et al., Nature (1989) 342:878-83; Abhinandanet al., Molecular Immunology (2008) 45(14):3832-39; MacCallum etWSGR Docket No. 63125-725.601\., JMolBiol. (1996) 262:732-45; or Honegger and Pliickthun, JMolBiol. (2001) 309(3):657-70. The CDR boundaries of various schemes are illustrated in Table 1, where the amino acid numbers are Kabat numbers unless otherwise indicated.Table 1. CDR Delineations According to Various Schemes CDR Kabat AbM Chothia Contact VL-CDR1 L24— L34 L24— L34 L26— L32 L30— L36 VL-CDR2 L50— L56 L50— L56 L50— L52 L46— L55 VL-CDR3 L89— L97 L89— L97 L91— L96 L89— L96 VH-CDR1 (Kabat nos.) H31— H35B H26— H35B H26— H32 H30— H35B VH-CDR1 (Chothia nos.) H31— H35 H26— H35 H26— H32 H30— H35 VH-CDR2 H50— H65 H50— H58 H53— H55 H47— H58 VH-CDR3 H95— H102 H95— H102 H95— H101 H93— H101
[0071] An antibody is said to “specifically bind” to an antigen X if the antibody binds to antigen X with a KD of 5 / 10sM or less, more preferably Izl0sM or less, more preferably 6 / | 09Mor less, more preferably 3 / | 09M or less, even more preferably 2 / | 09M or less. The antibody can be chimeric, humanized, or, preferably, human. The heavy chain constant region can be engineered to affect glycosylation type or extent, to extend antibody half-life, to enhance or reduce inter-actions with effector cells or the complement system, or to modulate some other property. The engineering can be accomplished by replacement, addition, or deletion of one or more amino acids or by replacement of a domain with a domain from another immunoglobulin type, or a combination of the foregoing.
[0072] The term “antigen binding fragment” and “antigen binding portion” of an antibody (or simply “antibody portion” or “antibody fragment”) mean one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody, such as (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CHI domains; (ii) aF(ab’)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fab ’ fragment, which is essentially an Fab with part of the hinge region (see, for example, Abbas et al., Cellular and Molecular Immunology, 6th Ed., Saunders Elsevier 2007); (iv) a Fd fragment consisting of the VH and CHI domains; (v) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (vi) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of a VH domain; (vii) an isolated complementarity determining region (CDR); and (viii) a nanobody, a heavy chain variable region containing a single variable domain and two constant domains. Preferred antigen binding fragments are Fab, F(ab’)2, Fab’, Fv, and Fd fragments. Furthermore, although the twoWSGR Docket No. 63125-725.601domains of the Fv fragment, VL and VH, are encoded by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv, or scFv); see, e.g., Bird et al. (1988) Science 242:423 -426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such single chain antibodies are also encompassed within the term “antigen-binding portion” of an antibody.
[0073] Antibody portions, such as Fab and F(ab’)2fragments, can be prepared from whole antibodies using conventional techniques, such as papain or pepsin digestion of whole antibodies. Moreover, antibodies, antibody portions and immunoadhesin molecules can be obtained using standard recombinant DNA techniques, e.g., as described herein.
[0074] In some embodiments, antibodies may originate from non-human sources and have been humanized to reduce anti-antibody immune responses. The term “humanize” refers to the fact that where an antibody is wholly or partially of non-human origin (for example, a murine or chicken antibody obtained from immunization of mice or chickens, respectively, with an antigen of interest, or a chimeric antibody based on such a murine or chicken antibody), it is possible to replace certain amino acids, in particular in the framework regions and constant regions of the heavy and light chains, in order to avoid or minimize an immune response in humans. Although it is not possible to precisely predict the immunogenicity, and thereby the human anti -antibody response, of a particular antibody, non-human antibodies tend to be more immunogenic in humans than human antibodies. Antibodies of non-human origin thus can be humanized to reduce the risk of a human anti-antibody response.
[0075] Humanization typically involves modification of the framework regions of the variable domain sequences. Amino acid residues that are part of complementarity determining regions (CDRs) most often will not be altered in connection with humanization, although in certain cases it may be desirable to alter individual CDR amino acid residues, for example to remove a glycosylation site, a deamidation site, an aspartate isomerization site or an undesired cysteine or methionine residue. N-linked glycosylation occurs by attachment of an oligosaccharide chain to an asparagine residue in the tripeptide sequence Asn-X-Ser or Asn-X-Thr, where X may be any amino acid except Pro. Removal of an N-glycosylation site may be achieved by mutating either the Asn or the Ser / Thr residue to a different residue, preferably by way of conservative substitution. Deamidation of asparagine and glutamine residues can occur depending on factors such as pH and surface exposure. Asparagine residues are particularly susceptible to deamidation, primarily when present in the sequence Asn-Gly, and to a lesser extent in other dipeptide sequences such as Asn-Ser, Asn-Thr, and Asn-Ala. When such a deamidation site, in particular Asn-Gly, is present in a CDR sequence, it may therefore beWSGR Docket No. 63125-725.601desirable to remove the site, typically by conservative substitution to remove one of the implicated residues.
[0076] The term “isolated antibody” means an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds antigen X is substantially free of antibodies that specifically bind antigens other than antigen X). An isolated antibody that specifically binds antigen X may, however, have cross -reactivity to other antigens, such as antigen X molecules from other species. In certain embodiments, an isolated antibody specifically binds to human antigen X and does not crossreact with other (non-human) antigen X antigens. Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.
[0077] The term “monoclonal antibody” or “monoclonal antibody composition” means a preparation of antibody molecules of single molecular composition, which displays a single binding specificity and affinity for a particular epitope.
[0078] The term “human antibody” means an antibody having variable regions in which both the framework and CDR regions (and the constant region, if present) are derived from human germline immunoglobulin sequences. Human antibodies may include later modifications, including natural or synthetic modifications. Human antibodies may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo). However, “human antibody” does not include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.
[0079] The term “human monoclonal antibody” means an antibody displaying a single binding specificity, which has variable regions in which both the framework and CDR regions are derived from human germline immunoglobulin sequences. In one embodiment, human monoclonal antibodies are produced by a hybridoma that includes a B cell obtained from a transgenic nonhuman animal, e.g., a transgenic mouse, having a genome comprising a human heavy chain transgene and a light chain transgene fused to an immortalized cell.
[0080] The term "epitope" refers to the amino acids conventionally bound by an immunoglobulin VH / VL pair, such as the antibodies, antigen binding portions thereof and other binding agents described herein. Other binding agents comprise non -antibody scaffolds. An epitope can be formed on a polypeptide from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents, whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes atWSGR Docket No. 63125-725.601least 3, and more usually, at least 5, about 9, or about 8-10 amino acids in a unique spatial conformation. An epitope defines the minimum binding site for an antibody, antigen binding portions thereof and other binding agent, and thus represents the target of specificity of an antibody, antigen binding portion thereof or other immunoglobulin -based binding agent. In the case of a single domain antibody, an epitope represents the unit of structure bound by a variable domain in isolation.
[0081] A “variant” antibody or antigen -binding portion has amino acid substitutions (which may be conservative or non-conservative) from a reference antibody or antigen -binding portion, but does not have substantially altered biologic activity from the reference antibody or antigenbinding portion. For example, the variant antibody or antigen -binding portion may retain at least 50%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% of the binding affinity of the reference antibody or antigen-binding portion, or may exceed the binding affinity of the reference antibody or antigen-binding portion.
[0082] The term “specifically binds” refers to the ability of a molecule (e.g., an antibody or antigen binding portion thereof or non-antibody scaffold) described herein to bind to a target with a KD of 10'5M (10000 nM) or less, e.g., 10’6M, 10’7M, 10’8M, 10’9M, 10-10M, 10-nM, 10'12M, or less. Specific binding can be influenced by, for example, the affinity and avidity of the antibody, antigen binding portion or other binding agent and the concentration of target polypeptide.
[0083] As used herein, the term “approximately” or “about” as applied to one or more values of interest refers to a value that is similar to a stated reference value. In certain embodiments, the term refers to a range of values that fall within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context.
[0084] The term “cleavable unit” refers to a chemical group that may be cleaved by action of an internal or external, preferably external, stimulus. The stimulus triggering the cleavage of the cleavable unit may be for instance pH or temperature conditions, or the presence of an enzyme. Cleavage of the cleavable unit preferably triggers self-immolation of the phenyl-comprising linker of the compounds of the invention, and release of the active agent D.
[0085] The term “cleavable sugar unit” or “sugar cleav able unit” can refer to a sugar moiety, preferably a glucuronide or a galactoside.
[0086] The term “peptide cleavable unit” can refer to a polypeptide, preferably a dipeptide or a tripeptide.WSGR Docket No. 63125-725.601Conjugates of the Disclosure
[0087] In an aspect, the present disclosure provides a conjugate of the Formula (XX):L'MI2S2R4“ S’.Y (K1)mD Formula (XX)or a pharmaceutically acceptable salt thereof, wherein;L is a Targeting Unit, wherein the Targeting Unit is an anti-5T4 antibody or an antigenbinding portion thereof;(K2-(S4)p)nR40is independently selected from hydrogen, Y, andD is selected from a Drug unit;n is selected from 0 and 1;m is selected from 0 and 1;wherein at least n or m is 1;p is selected from 0 and 1;z is selected from 0 and 1;X is selected from CH and N;Y is a -O-T1and -NH-T2;T1is a sugar cleavable unit;T2 is peptide cleavable unit;S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Ci0carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;WSGR Docket No. 63125-725.601S2is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C3o alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-— S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Ci0carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;54is selected from: (i) an optionally substituted Ci-C3o alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;(ii) Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, C3.io carbocycle and 3-to 10-membered heterocycle; and(iii) C3.io carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6alkynyl;M2is a connector unit;K1is selected from:(i) a peptide unit,WSGR Docket No. 63125-725.601(ii) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)--S(O)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;K2is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C3o alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)--S(O)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;each R20is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3.i2 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.i2carbocycle, and 3- to 12-membered heterocycle; andeach R30is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3.i2carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci.10 alkyl, -C O haloalkyl, -O-C O alkyl, oxo, C3.i2 carbocycle, and 3- to 12-membered heterocycle.
[0088] In some cases, for a conjugate or salt of Formula (XX), L is an anti-5T4 antibody or an antigen-binding portion thereof.
[0089] In some cases, for a conjugate or salt of Formula (XX), when Xis CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.
[0090] In an aspect, the present disclosure provides a conjugate of the Formula (XX):WSGR Docket No. 63125-725.601M2D Formula (XX)or a pharmaceutically acceptable salt thereof, wherein;(K2-(S4)p)nr^\ x(Y)Z4- £R40is independently selected from hydrogen, Y, andD is selected from a Drug unit;n is selected from 0 and 1;m is selected from 0 and 1;wherein at least n or m is 1;p is selected from 0 and 1;z is selected from 0 and 1;X is selected from CH and N;Y is a -O-T1and -NH-T2;T1IS a sugar cleavable unit;T2 IS peptide cleavable unit;S1is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30 alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii)WSGR Docket No. 63125-725.601optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-— S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Ci0carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;54is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C3o alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;(ii) Ci-io alkyl, C2-io alkenyl, C2.io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, C3.io carbocycle and 3-to 10-membered heterocycle; and(iii) C3.io carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6 alkynyl;L is a Targeting Unit;M2is a connector unit;K1is selected from:(i) a peptide unit,(ii) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2- or -P(O)(R20)2-;WSGR Docket No. 63125-725.601(iii) an oligosaccharide; and(iv) a poly ether; wherein when Xis CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a poly sarcosine, the poly sarcosine contains 2-9 sarcosines or 13-30 sarcosines;K2is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, -S(O)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;each R20is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.12 carbocycle, and 3- to 12-membered heterocycle; andeach R30is independently selected from hydrogen; and Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C3.12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, C O alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.12 carbocycle, and 3- to 12-membered heterocycle.
[0091] In an aspect, the present disclosure provides a conjugate of the Formula (A):DFormula (A)or a pharmaceutically acceptable salt thereof, wherein;L is a Targeting Unit;D is selected from a Drug unit;n is selected from 0 and 1;m is selected from 0 and 1;wherein at least n or m is 1;p is selected from 0 and 1;WSGR Docket No. 63125-725.601X is selected from CH and N;Y is a -O-T1and -NH-T2;T1is a sugar cleavable unit;T2is peptide cleavable unit;S1is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C3o alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-— S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Cio carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;S2is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C3o alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Cio carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;54is selected from: (i) an optionally substituted Ci-C3o alkylene wherein one or more alkylene units of the Ci-C3o alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;WSGR Docket No. 63125-725.601(ii) Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and(iii) C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6 alkynyl;M2is a connector unit;K1is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;K2is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2- or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;each R20is independently selected from hydrogen; and Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C3.i2carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -N02, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -0-C O alkyl, oxo, C3.i2carbocycle, and 3- to 12-membered heterocycle; andeach R30is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -N02, -NH2, -WSGR Docket No. 63125-725.601N(CI-6alkyl)2, Cuo alkyl, -C O haloalkyl, -O-C O alkyl, oxo, C3.12 carbocycle, and 3- to 12-membered heterocycle.
[0092] In some embodiments, for a conjugate or salt of Formula (A), wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.
[0093] In some embodiments, for a conjugate or salt of Formula (A), the Targeting Unit is an anti-5 T4 antibody or an antigen -binding portion thereof.
[0094] In an aspect, the present disclosure provides a conjugate of the Formula (Aa) or Formula (Ab):Formula (Aa),Formula (Ab), oror a pharmaceutically acceptable salt thereof, wherein;D is selected from a Drug unit;n is selected from 0 and 1;m is selected from 0 and 1;wherein at least n or m is 1;p is selected from 0 and 1;X is selected from CH and N;Y is a -O-T1and -NH-T2;T1is a sugar cleavable unit;T2is peptide cleavable unit;S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -WSGR Docket No. 63125-725.601C(0)0-, -S-, — S(0)—, — S(0)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C3o alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-— S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Cio carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;S2is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C3o alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Cio carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;54is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;(ii) Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, C3.io carbocycle and 3-to 10-membered heterocycle; and(iii) C3.io carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -WSGR Docket No. 63125-725.601N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6 alkynyl;L is a Targeting Unit;M2is a connector unit;K1is selected from:(i) a peptide unit,(ii) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2-, or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;K2is selected from:(i) a peptide unit,(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2-, or -P(O)(R20)2-;(iii) an oligosaccharide; and(iv) a polyether;each R20is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -N02, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -0-C O alkyl, oxo, C3.i2carbocycle, and 3- to 12-membered heterocycle; andeach R30is independently selected from hydrogen; and Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -N02, -NH2, -N(CI-6 alkyl)2, Ci.10 alkyl, -C O haloalkyl, -0-C O alkyl, oxo, C3-12 carbocycle, and 3- to 12-membered heterocycle.
[0095] In some embodiments, for a conjugate or salt of Formula (Aa) or Formula (Ab): when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a poly sarcosine, the poly sarcosine contains 2-9 sarcosines or 13-30 sarcosines.WSGR Docket No. 63125-725.601
[0096] In some embodiments, for a conjugate or salt of Formula (Aa) or Formula (Ab): the Targeting Unit is an anti-5 T4 antibody or an antigen-binding portion thereof;
[0097] In some embodiments, for a conjugate of Formula (A), Formula (Aa), Formula (Ab), Formula (XX), or Formula (XXIII), n is 0. In some cases, n is 1.
[0098] In some embodiments, for a conjugate of Formula (A), Formula (Aa), Formula (Ab), Formula (XX), or Formula (XXIII), p is 0. In some cases, p is 1.
[0099] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), or Formula (A -4), S1is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, -S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, or -P(O)(R20)2-. In some cases, S1is selected from: (i) an optionally substituted Ce-Cio alkylene wherein one or more alkylene units of the C6-Ci0alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-. In some cases, S1is an optionally substituted Ci alkylene. In some cases, S1is an optionally substituted C2alkylene. In some cases, S1is an optionally substituted C3alkylene. In some cases, S1is an optionally substituted C4alkylene. In some cases, S1is an optionally substituted C5alkylene. In some cases, S1is an optionally substituted C6alkylene. In some cases, S1is an optionally substituted C7alkylene. In some cases, S1is an optionally substituted C8alkylene. In some cases, S1is an optionally substituted C9alkylene. In some cases, S1is an optionally substituted C10 alkylene. In some cases, S1is an optionally substituted Cn alkylene. In some cases, S1is an optionally substituted Ci2alkylene. In some cases, S1is an optionally substituted Ci3alkylene. In some cases, S1is an optionally substituted C14 alkylene. In some cases, S1is an optionally substituted C15 alkylene. In some cases, S1is an optionally substituted Ci6alkylene. In some cases, S1is an optionally substituted Ci7alkylene. In some cases, S1is an optionally substituted Ci8alkylene. In some cases, S1is an optionally substituted C 19 alkylene. In some cases, S1is an optionally substituted C2o alkylene. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, -S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, or -P(O)(R20)2-. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by -N(R20)-. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by -N(R20)C(O)-. In some cases, the one or more alkylene units ofWSGR Docket No. 63125-725.601the alkylene of S1are optionally and independently replaced by -C(O)N(R20)-. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by — C(O)~. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by -O-. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S1are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene has no repeating heteroatom s of adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit has no -N-N- or -O-O-. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resulting alkylene has only 1 heteroatom. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 2 replaced units. In some cases, the alkylene has 3 replaced units. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 5 replaced units. In some cases, the alkylene has 6 replaced units. In some cases, no adjacent alkylene units of the alkylene are replaced. In some cases, no adjacent alkylene units resulting in two or more adjacent heteroatoms are present in the resulting alkylene (e.g., adjacent -N(R20)S(O)2- and -N(R20)- are not allowed, but the singular -N(R20)S(O)2- is allowed). In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, a resulting alkylene has two heteroatoms, the two heteroatoms are from a singular replaced alkylene unit. In some cases, there are two heteroatoms in a resulting alkylene if they result from a singular replacement of an alkylene unit. In some cases, the optional substituents on S1are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), and -CN; (ii) CMO alkyl, C2.WSGR Docket No. 63125-725.601io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, the optional substituents on S1are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN. In some cases, the optional substituents on S1are independently selected at each occurrence from: halogen, -OR30, -N(R30)2, =0, and -CN. In some cases, the optional substituents on S1are independently selected at each occurrence from: =0.
[0100] In some embodiments, for a conjugate or salt of Formula (XX), Formula (A), Formula (Aa), Formula (Ab), or Formula (A-l), whereinX is CH;NH NH,, OI rl IIHN HNS1is selected fromS2is selected fromS3is absent;M2is 0;n is 0;m is 1;Y is selected from a cleavable sugar and cleavable peptide (e.g., dipeptide);K1is selected from a peptide unit and oligosaccharide; andWSGR Docket No. 63125-725.601Dis
[0101] In some embodiments, for a conjugate or salt of Formula (XX), Formula (A), Formula (Aa), Formula (Ab), or Formula (A-l), whereinX is CH:NH H 9HN HNS1is selected fromOS2is selected fromS3is absent;M2is 0;n is 0;m is 1;Y is selected from a cleavable sugar and cleavable peptide (e.g., dipeptide);K1is selected from a peptide unit; andDis
[0102] In some embodiments, for a conjugate or salt of Formula (XX), Formula (A), Formula (Aa), Formula (Ab), or Formula (A-l), whereinX is CH;WSGR Docket No. 63125-725.601S3is absent;m is 1;NH2WSGR Docket No. 63125-725.601
[0103] In some embodiments, for a conjugate or salt of Formula (XX), Formula (A), Formula (Aa), Formula (Ab), or Formula (A-l), whereinX is CH;n is 0;m is 1;WSGR Docket No. 63125-725.601
[0104] In some embodiments, for a conjugate or salt of Formula (XX), Formula (A), Formula (Aa), Formula (Ab), or Formula (A-l), whereinX is CH;WSGR Docket No. 63125-725.601n is 0; m is 1;WSGR Docket No. 63125-725.601
[0105] In some embodiments, for a conjugate or salt of Formula (XX), Formula (A), Formula (Aa), Formula (Ab), or Formula (A-l), whereinS3is absent;WSGR Docket No. 63125-725.601; andWSGR Docket No. 63125-725.601
[0106] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S1is a branched alkylene.
[0107] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S1
[0108] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S1is NH HNOrepresented by ' O
[0109] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII),wherein S^K1is represented by is represented by
[0110] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S2is selected from: (i) an optionally substituted Cs-Cn alkyleneWSGR Docket No. 63125-725.601wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, and -C(O)-. In some cases, S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- -S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-— S(O)2—, or-P(O)(R20)2-. In some cases, S2is selected from: (i) an optionally substituted Ce-Cio alkylene wherein one or more alkylene units of the C6-Ci0alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-. In some cases, S2is an optionally substituted Ci alkylene. In some cases, S2is an optionally substituted C2alkylene. In some cases, S2is an optionally substituted C3 alkylene. In some cases, S2is an optionally substituted C4alkylene. In some cases, S2is an optionally substituted C5alkylene. In some cases, S2is an optionally substituted C6alkylene. In some cases, S2is an optionally substituted C7 alkylene. In some cases, S2is an optionally substituted C8alkylene. In some cases, S2is an optionally substituted C9alkylene. In some cases, S2is an optionally substituted C10 alkylene. In some cases, S2is an optionally substituted Cn alkylene. In some cases, S2is an optionally substituted C12 alkylene. In some cases, S2is an optionally substituted C13 alkylene. In some cases, S2is an optionally substituted C14 alkylene. In some cases, S2is an optionally substituted Ci5alkylene. In some cases, S2is an optionally substituted Ci6alkylene. In some cases, S2is an optionally substituted Ci7alkylene. In some cases, S2is an optionally substituted Ci8alkylene. In some cases, S2is an optionally substituted Ci9alkylene. In some cases, S2is an optionally substituted C20alkylene. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)-, -S(O)2- or -P(O)(R20)2-. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by -N(R20)-. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by -N(R20)C(O)-. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by -C(O)N(R20)-. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by -C(O)-. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by -O-. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S2are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, theWSGR Docket No. 63125-725.601adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit has no -N-N- or -O-O-. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resulting alkylene has only 1 heteroatom. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 4 heteroatoms, wherein the 4 heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 2 replaced units. In some cases, the alkylene has 3 replaced units. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 5 replaced units. In some cases, the optional substituents on S2, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2.io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, the optional substituents on S2, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, the optional substituents on S2, are independently selected at each occurrence from: halogen, -OR30, -N(R30)2, =0, and -CN. In some cases, the optional substituents on S2, are independently selected at each occurrence from: =0. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, a resulting alkylene has two heteroatoms, the two heteroatoms areWSGR Docket No. 63125-725.601from a singular replaced alkylene unit. In some cases, there are two heteroatoms in a resulting alkylene if they result from a singular replacement of an alkylene unit.
[0111] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l ), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S2is a linear alkylene.
[0112] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula O0(XXII), or Formula (XXIII), S2is represented by. In some cases, S2is
[0113] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (XX), or Formula (XXIII), X is CH.
[0114] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (XX), or Formula (XXIII), X is N.
[0115] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker or salt of Formula (I), Formula (LAA), Formula (LAB), Formula (LA), Formula (la), Formula (I-AAa), Formula (lb), Formula (LAAb), Formula (ILA), Formula (ILB), Formula (ILC), Formula (ILCA), Formula (ILD), Formula (ILG), Formula (X), Formula (XI), Formula (XII), Formula (XIII) or for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), Formula (A-4), Formula (XX), Formula (XXI), Formula (XXII), or Formula (XXIII), S1is selected from: (i) an optionally substituted C4-C10 alkylene wherein one or more alkylene units of the C4-C10 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-.WSGR Docket No. 63125-725.601
[0116] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), or Formula (A-4), S1is selected from: (i) an optionally substituted C1-C3 alkylene wherein one or more alkylene units of the C1-C3 alkylene are optionally and independently replaced by -N(R20)-. In some cases, S1is selected from: (i) an optionally substituted Ci-C2alkylene wherein one or more alkylene units of the Ci-C2alkylene are optionally and independently replaced by -N(R20)-. In some cases, S1is selected from: (i) an optionally substituted C2-C3alkylene wherein one or more alkylene units of the C2-C3alkylene are optionally and independently replaced by -N(R20)-. In some cases, S1is selected from 1-4H. In some cases, S1is represented byH
[0117] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa),■^NH HN. ^61-4 v^ ° Formula (Ab), Formula (A-3), or Formula (A-4), S1is selected from'. In some^NHcases, S1is represented by0
[0118] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), or Formula (A-4), S2is selected from: (i) an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, and -C(O)-. In some
[0119] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), or Formula (A-4), S2is selected from: (i) an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-Ci2alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, and -C(O)-. In someWSGR Docket No. 63125-725.601cases, S2is selected fromO. In some cases, S2is represented byO. In some cases, S2is represented byO
[0120] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), or Formula (A-4), S2is a linear alkylene.
[0121] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l),Formula (A-3), or Formula (A-4), S2is represented by some cases, S2
[0122] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), or Formula (A-4), S^S2is represented byWSGR Docket No. 63125-725.601
[0123] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), or Formula (A-4), S^S^M1is represented byO H N NN, wherein S3is absent.
[0124] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), or Formula (A-4), S3is present and is a phenylene.
[0125] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), or Formula (A-4), S3is absent.
[0126] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), the sugar cleavable unit of T1includes a sugar. In some cases, the sugar is glucuronide. In some cases, the sugar is selected from fructose, galactose, glucose, xylose and ribose. In some cases, the sugar is a monosaccharide. In some cases, the sugar is a disaccharide. In some cases, the P-glucuronidase enzyme in lysosomes or the tumor interstitium cleaves the drug-linker between the sugar and the oxygen bond, releasing the drug.
[0127] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), Y isOH
[0128] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the peptide unit of T2includes one or more amino acids selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P -Alanine. In some cases, the peptide unit of T2includes one or more amino acids selected from a group consisting of alanine, arginine, asparagine, aspartic acid, glutamine, glycine, lysine, methionine, phenylalanine, proline, serine, valine, citrulline, and P-Alanine. In some cases, the peptide unit of T2includes a dipeptide orWSGR Docket No. 63125-725.601tripeptide. In some cases, the peptide unit of T2includes a dipeptide. In some cases, the dipeptide is selected from Val-Cit, Vai-Ala and Phe-Lys. In some cases, Cathepsin B is a lysosomal cysteine protease that is highly up-regulated in malignant cells. In some cases, the peptide cleavable unit is cleaved by Cathepsin B.
[0129] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the peptide unit of T2includes a capping moiety. In some cases, the capping moiety is a moiety capable of reacting with an amine of the peptide to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide. In some cases, the capping moiety is a moiety Owhich caps the end of an peptide / amino acid. In some cases, the capping moiety is. In
[0130] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), K1is not a polysarcosine. In some cases, K1does not include adjacent sarcosines. In some cases, when K1includes a sarcosine, there is at least one other amino acid present. In some cases, when a peptide unit includes a sarcosine, there is at least one other amino acid present.
[0131] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), K1includes PASylation. In some cases, PASylation is a peptide comprising proline, alanine, and serine. In some cases, PASylation is a peptide consisting of only proline, alanine, and serine. In some cases, K1includes PASylation of less than PAS100. For example, PAS100 refers to a peptide having 100 amino acids, wherein the amino acids are selected from proline, alanine, and serine. In some cases, K1includes PASylation of less than PAS50. In some cases, K1includes PASylation of less than PAS25. In some cases, K1includes PASylation of more than PAS5. In some cases, K1includes PASylation of more thanPAS9. In some cases, K1includes PASylation of more than PAS15. In some cases, K1includes PASylation of PAS5 to PAS25. In some cases, K1includes PASylation of PAS10 to PAS20. In some cases, K1includes PASylation of PAS10.WSGR Docket No. 63125-725.601In some cases, K1includes PASylation of PAS20. In some cases, K1includes a beta-alanine that links the PASylation to the drug-linker. In some cases, PASylation is used to extend the plasma half-life. In some cases, PASylation is used to increase solubility. In some cases, PASylation is used to increase solubility without generating secondary structures. In some cases, PASylation issome cases, PASylation is
[0132] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), K1is not a poly sarcosine. In some cases, K1includes adjacent sarcosines. In some cases, when K1includes a sarcosine, there is at least one other amino acid present. In some cases, when K1includes adjacent sarcosines, there is at least one other amino acid present. In some cases, when a peptide unit includes a sarcosine, there is at least one other amino acid present. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, K1includes a glycine and two adjacent sarcosines. In some cases, K1includes a glycine and three adjacent sarcosines. In some cases, K1includes a glycine and four adjacent sarcosines. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K1is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K1includes 2 glycines and 8 sarcosines. In some cases, K1includes 3 glycines and 8 sarcosines. In some cases, K1includes 4 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 6 sarcosines. In some cases, K1includes 3 glycines and 5 sarcosines. In some cases, K1includes 3 glycines and 4 sarcosines. In some cases, K1includes 3 glycines and 3 sarcosines. In some cases, K1includes 3 glycines and 9 sarcosines. In some cases, K1includes 3 glycines and 10 sarcosines. In some cases, K1includes 5 glycines and 5 sarcosines. In some cases, K1includes 4 glycines and 4 sarcosines. In some cases, K1includes 4 glycines and 5 sarcosines. In some cases, K1includes 5 glycines and 4 sarcosines. In some cases, K1has at most 9 sarcosines. In some cases, K1has at most 8 sarcosines. In some cases, K1has at most 7 sarcosines. In some cases, K1has at most 6 sarcosines. In some cases, K1has at most 5 sarcosines. In some cases, K1has at most 4 sarcosines. In some cases, K1has at most 3 sarcosines. In some cases, K1has at most 2 sarcosines. In some cases, K1has at most 1WSGR Docket No. 63125-725.601sarcosine. In some cases, K1has at most 9 glycines. In some cases, K1has at most 8 glycines. In some cases, K1has at most 7 glycines. In some cases, K1has at most 6 glycines. In some cases, K1has at most 5 glycines. In some cases, K1has at most 4 glycines. In some cases, K1has at most 3 glycines. In some cases, K1has at most 2 glycines. In some cases, K1has at most 1 glycine.
[0133] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), each K1is selected from a peptide unit. In some cases, the peptide unit of K1has 1 to 50 amino acids. In some cases, the peptide unit of K1has 1 to 20 amino acids. In some cases, the peptide unit of K1has 1 to 10 amino acids. In some cases, the peptide unit of K1has 2 to 50 amino acids. In some cases, the peptide unit of K1has 2 to 40 amino acids. In some cases, the peptide unit of K1has 2 to 30 amino acids. In some cases, the peptide unit of K1has 2 to 20 amino acids. In some cases, the peptide unit of K1has 2 to 10 amino acids. In some cases, the peptide unit of K1has 5 to 10 amino acids. In some cases, the peptide unit of K1has at least 1 amino acids. In some cases, the peptide unit of K1has 1 amino acid. In some cases, the peptide unit of K1has at least 2 amino acids. In some cases, the peptide unit of K1has at least 5 amino acids. In some cases, the peptide unit of K1has at least 8 amino acids. In some cases, the peptide unit of K1has at least 10 amino acids. In some cases, the peptide unit of K1has at most 10 amino acids. In some cases, the peptide unit of K1has 10 amino acids. In some cases, the peptide unit of K1has at least 12 amino acids. In some cases, the peptide unit of K1has at most 12 amino acids. In some cases, the peptide unit of K1has at least 20 amino acids. In some cases, the peptide unit of K1has at most 20 amino acids. In some cases, the peptide unit of K1has 20 amino acids. In some cases, the peptide unit of K1has at most 30 amino acids. In some cases, the peptide unit of K1has at least 30 amino acids. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine,WSGR Docket No. 63125-725.601sarcosine, proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and P -Alanine. In some cases, the amino acids of K1is selected from a group consisting of proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K1includes at least one glycine and at least one other amino acid. In some cases, the amino acids of K1includes at least one glycine and at least one sarcosine. In some cases, the amino acids ofK1includes at least one glycine and at least one other amino acid selected from proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and P-Alanine. In some cases, K1includes at least one glycine. In some cases, K1includes at least one proline. In some cases, K1includes at least one serine. In some cases, K1includes at least one alanine. In some cases, K1includes at least one P-Alanine.
[0134] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), each K1is selected from a peptide unit. In some cases, the peptide unit of K1has 1 to 50 amino acids. In some cases, the peptide unit of K1has 1 to 20 amino acids. In some cases, the peptide unit of K1has 1 to 10 amino acids. In some cases, the peptide unit of K1has 2 to 50 amino acids. In some cases, the peptide unit of K1has 2 to 40 amino acids. In some cases, the peptide unit of K1has 2 to 30 amino acids. In some cases, the peptide unit of K1has 2 to 20 amino acids. In some cases, the peptide unit of K1has 2 to 10 amino acids. In some cases, the peptide unit of K1has 5 to 10 amino acids. In some cases, the peptide unit of K1has at least 1 amino acids. In some cases, the peptide unit of K1has 1 amino acid. In some cases, the peptide unit of K1has at least 2 amino acids. In some cases, the peptide unit of K1has at least 5 amino acids. In some cases, the peptide unit of K1has at least 8 amino acids. In some cases, the peptide unit of K1has at least 10 amino acids. In some cases, the peptide unit of K1has at most 10 amino acids. In some cases, the peptide unit of K1has 10 amino acids. In some cases, the peptide unit of K1has at least 12 amino acids. In some cases, the peptide unit of K1has at most 12 amino acids. In some cases, the peptide unit of K1has at least 20 amino acids. In some cases, the peptide unit of K1has at most 20 amino acids. In some cases, the peptide unit of K1has 20 amino acids. In some cases, the peptide unit of K1has at most 30 amino acids. In some cases, the peptide unit of K1has at least 30 amino acids. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K1is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, K1includes a glycine and two adjacent sarcosines. InWSGR Docket No. 63125-725.601some cases, K1includes a glycine and three adjacent sarcosines. In some cases, K1includes a glycine and four adjacent sarcosines. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K1is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K1includes 2 glycines and 8 sarcosines. In some cases, K1includes 3 glycines and 8 sarcosines. In some cases, K1includes 4 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 6 sarcosines. In some cases, K1includes 3 glycines and 5 sarcosines. In some cases, K1includes 3 glycines and 4 sarcosines. In some cases, K1includes 3 glycines and 3 sarcosines. In some cases, K1includes 3 glycines and 9 sarcosines. In some cases, K1includes 3 glycines and 10 sarcosines. In some cases, K1includes 5 glycines and 5 sarcosines. In some cases, K1includes 4 glycines and 4 sarcosines. In some cases, K1includes 4 glycines and 5 sarcosines. In some cases, K1includes 5 glycines and 4 sarcosines. In some cases, K1has at most 9 sarcosines. In some cases, K1has at most 8 sarcosines. In some cases, K1has at most 7 sarcosines. In some cases, K1has at most 6 sarcosines. In some cases, K1has at most 5 sarcosines. In some cases, K1has at most 4 sarcosines. In some cases, K1has at most 3 sarcosines. In some cases, K1has at most 2 sarcosines. In some cases, K1has at most 1 sarcosine. In some cases, K1has at most 9 glycines. In some cases, K1has at most 8 glycines. In some cases, K1has at most 7 glycines. In some cases, K1has at most 6 glycines. In some cases, K1has at most 5 glycines. In some cases, K1has at most 4 glycines. In some cases, K1has at most 3 glycines. In some cases, K1has at most 2 glycines. In some cases, K1has at most 1 glycine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids ofK1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K1WSGR Docket No. 63125-725.601includes at least one glycine and at least one other amino acid. In some cases, the amino acids of K1includes at least one glycine and at least one sarcosine. In some cases, the amino acids of K1includes at least one glycine and at least one other amino acid selected from proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and P-Alanine. In some cases, K1includes at least one glycine. In some cases, K1includes at least one proline. In some cases, K1includes at least one serine. In some cases, K1includes at least one alanine. In some cases, K1includes at least one P-Alanine.
[0135] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker or salt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (LAB), Formula (LA), Formula (la), Formula (LAAa), Formula (lb), Formula (LAAb), Formula (LB), Formula (ILC), Formula (ILCA), Formula (ILD), or for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), K1is selected from a peptide unit, wherein the peptide unit has a terminal -NH2. In some cases, K1is selected from a peptide unit, wherein the peptide unit has a terminal -OH. In some cases, K1is selected from a peptide, wherein the peptide has a terminal -NH2. In some cases, K1is selected from a peptide, wherein the peptide has a terminal -OH.
[0136] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), peptide unit ofWSGR Docket No. 63125-725.601wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In somewherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), -CN, C3.10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, andZH ' / SX)H°. In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6isN °'s°H d'0H
[0137] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), K1is selectedWSGR Docket No. 63125-725.601some cases, K1is selected from In some cases, K1is selected from° s°6'0HIn some cases, K1is selected from some cases, K1is selected fromcases, K1is selected fromWSGR Docket No. 63125-725.601
[0138] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the peptideunit of K1has a terminus unit. In some cases, K1is selected fromwherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some u O | Ocases, K1is selected from J, JOwherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or moreWSGR Docket No. 63125-725.601substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, andA LJZ'S^OH1-1O in some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6isN ° s°H d'0H
[0139] In some embodiments, for a Linker or salt of Formula (III), or for a Drug-Linker or salt of Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (I), Formula (I-AA), Formula (LAB), Formula (LA), Formula (la), Formula (LAAa), Formula (lb), Formula (LAAb), Formula (LB), Formula (ILC), Formula (ILCA), Formula (ILD), or for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa),WSGR Docket No. 63125-725.601K1is selected from. In some cases, K1is selected fromIn some cases, K1is selected fromcases, K1is selected fromWSGR Docket No. 63125-725.601. In some cases, K1is selected fromcases, K1is selected fromcases, K1is selected fromcases, K1is selected fromWSGR Docket No. 63125-725.601. In some cases, K1is selected fromIn some cases, K1is selected fromIn some cases, K1is selected fromcases, K1is selected fromis selected from
[0140] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), the peptideunit of K1has a terminus unit. In some cases, K1is selected fromWSGR Docket No. 63125-725.601wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, K1is selected fromwherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In someWSGR Docket No. 63125-725.601cases, K1is selected fromwherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, andZH / " OH0. In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6isN °'s°H d'0H
[0141] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), Formula (A-7), or Formula (A-8), each K1isWSGR Docket No. 63125-725.601selected from: an oligosaccharide. In some cases, each K1is selected from:, wherein k is selected from 2 to 10. In some cases, each K1isselected from:K, wherein k is selected from 2 to 10. In some cases, kis 2. In some cases, k is 3. In some cases, kis 4. In some cases, k is 5. In some cases, kis 6. In some cases, each K1is selected from:. In some cases,each K1is selected from:
[0142] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l),or Formula (A-2), S1is represented byWSGR Docket No. 63125-725.601, and K1is an oligosaccharide. In some cases, S1isand
[0143] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), K2is selected from a peptide unit. In some cases, the peptide unit is a residue. In some cases, the peptide unit of K2has 1 to 50 amino acids. In some cases, the peptide unit of K2has 1 to 20 amino acids. In some cases, the peptide unit of K2has 1 to 10 amino acids. In some cases, the peptide unit of K2has 2 to 50 amino acids. In some cases, the peptide unit of K2has 2 to 40 amino acids. In some cases, the peptide unit of K2has 2 to 30 amino acids. In some cases,WSGR Docket No. 63125-725.601the peptide unit of K2has 2 to 20 amino acids. In some cases, the peptide unit of K2has 2 to 10 amino acids. In some cases, the peptide unit of K2has 5 to 10 amino acids. In some cases, the peptide unit of K2has at least 1 amino acid. In some cases, the peptide unit of K2has 1 amino acid. In some cases, the peptide unit of K2has at least 2 amino acids. In some cases, the peptide unit of K2has at least 5 amino acids. In some cases, the peptide unit of K2has at least 8 amino acids. In some cases, the peptide unit of K2has at least 10 amino acids. In some cases, the peptide unit of K2has at most 10 amino acids. In some cases, the peptide unit of K2has 10 amino acids. In some cases, the peptide unit of K2has at least 12 amino acids. In some cases, the peptide unit of K2has at most 12 amino acids. In some cases, the peptide unit of K2has at least 20 amino acids. In some cases, the peptide unit of K2has at most 20 amino acids. In some cases, the peptide unit of K2has 20 amino acids. In some cases, the peptide unit of K2has at most 30 amino acids. In some cases, the peptide unit of K2has at least 30 amino acids. In some cases, the amino acids of K2are selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K2are selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K2are selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine. In some cases, the amino acids of K2are selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K2are selected from a group consisting of sarcosine, proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K2are selected from a group consisting of glycine, proline, serine, alanine, and P-Alanine. In some cases, the amino acids of K2are selected from a group consisting of glycine, proline, serine, alanine, and P-Alanine. In some cases, K2includes at least one glycine. In some cases, K2includes at least one proline. In some cases, K2includes at least one serine. In some cases, K2includes at least one alanine. In some cases, K2includes at least one P-Alanine. In some cases, K2is a polysarcosine. In some cases, K2is a polysarcosine with ten repeating sarcosine units. In some cases, the amino acids of K2includes at least one glycine and at least one amino acid. In some cases, the amino acids of K2includes at least one glycine and at least one amino acid selected from sarcosine, proline, serine, alanine, and P-Alanine.WSGR Docket No. 63125-725.601
[0144] In some embodiments, for a conjugate or salt of Formula (A), Formula (Aa), Formula (Ab), Formula (A-l ), or Formula (A-2), K2K2is not a poly sarcosine. In some cases, K2includes adjacent sarcosines. In some cases, when K2includes a sarcosine, there is at least one other amino acid present. In some cases, when K2includes adjacent sarcosines, there is at least one other amino acid present. In some cases, when a peptide unit includes a sarcosine, there is at least one other amino acid present. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, K2includes a glycine and two adjacent sarcosines. In some cases, K2includes a glycine and three adjacent sarcosines. In some cases, K2includes a glycine and four adjacent sarcosines. In some cases, K2is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K2is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K2is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K2includes 2 glycines and 8 sarcosines. In some cases, K2includes 3 glycines and 8 sarcosines. In some cases, K2includes 4 glycines and 7 sarcosines. In some cases, K2includes 3 glycines and 7 sarcosines. In some cases, K2includes 3 glycines and 6 sarcosines. In some cases, K2includes 3 glycines and 5 sarcosines. In some cases, K2includes 3 glycines and 4 sarcosines. In some cases, K2includes 3 glycines and 3 sarcosines. In some cases, K2includes 3 glycines and 9 sarcosines. In some cases, K2includes 3 glycines and 10 sarcosines. In some cases, K2includes 5 glycines and 5 sarcosines. In some cases, K2includes 4 glycines and 4 sarcosines. In some cases, K2includes 4 glycines and 5 sarcosines. In some cases, K2includes 5 glycines and 4 sarcosines. In some cases, K2has at most 9 sarcosines. In some cases, K2has at most 8 sarcosines. In some cases, K2has at most 7 sarcosines. In some cases, K2has at most 6 sarcosines. In some cases, K2has at most 5 sarcosines. In some cases, K2has at most 4 sarcosines. In some cases, K2has at most 3 sarcosines. In some cases, K2has at most 2 sarcosines. In some cases, K2has at most 1 sarcosine. In some cases, K2has at most 9 glycines. In some cases, K2has at most 8 glycines. In some cases, K2has at most 7 glycines. In some cases, K2has at most 6 glycines. In some cases, K2has at most 5 glycines. In some cases, K2has at most 4 glycines. In some cases, K2has at most 3 glycines. In some cases, K2has at most 2 glycines. In some cases, K2has at most 1 glycine.
[0145] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), the peptide unit of K2has a terminus unit. In some cases, K2is selected fromWSGR Docket No. 63125-725.601wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), -CN, C3.10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, andA LJ X °'S'0H. In some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6isN >■ / H 6'OH
[0146] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), the peptide unit of K2has a terminus unit. In some cases, K2is selected fromWSGR Docket No. 63125-725.601owherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In somewherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen;WSGR Docket No. 63125-725.601Ci-io alkyl, C2-io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, andZ ftHO in some cases, R6is -OH. In some cases, R6is -NH2. In some cases, R6isN °'s°H d'0H
[0147] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), orFormula (A-6), K2is selected fromWSGR Docket No. 63125-725.601some cases, K2is selected fromIn some cases, K2is selected fromIn some cases, K2is selected fromsome cases, K2is selected fromcases, K2is selected from
[0148] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), orWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601. In some cases, K2is selected fromIn some cases, K2is selected from. In some cases, K2isNH2. In some cases, K2is selected from. In some cases, K2is selected fromWSGR Docket No. 63125-725.601In some cases, K2is selected fromcases, K2is selected fromcases, K2is selected from
[0149] In some embodiments, for a conjugate or salt of Formula (X), Formula (XIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), each K2is selected from: an oligosaccharide. In some cases, each K2is selectedfrom:k, wherein k is selected from 2 to 10. In some cases, k is 2. In some cases, k is 3. In some cases, k is 4. In some cases, k is 5. In some cases, k is 6. In someWSGR Docket No. 63125-725.601cases, each K2is selected from:3. In some cases, each K2is selected
[0150] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), K1is a hydrophilic spacer. In some cases, K1is selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, K1is selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, K1is selected from hydrophilic peptides and polysaccharides. In some cases, K1is selected from hydrophilic peptides. In some cases, K1is selected from polysaccharides. In some cases, cases K1is a half-life promoting substituent. In some cases, the half-life promoting substituent increases the half-life of the drug. In some cases, the half-life promoting substituent increases the half-life of the conjugate.
[0151] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), K2is a hydrophilic spacer. In some cases, K2is selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, K2is selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, K2is selected from hydrophilic peptides and polysaccharides. In some cases, K2is selected from hydrophilic peptides. In some cases, K2is selected from polysaccharides. In some cases, cases K2is a half-life promoting substituent. In some cases, the half-life promoting substituent increases the half-life of the drug. In some cases, the half-life promoting substituent increases the half-life of the conjugate. In some cases, p is 1.
[0152] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), Formula (A-6), K2includes PASylation. In some cases, PASylation is a peptide comprisingWSGR Docket No. 63125-725.601proline, alanine, and serine. In some cases, PASylation is a peptide consisting of only proline, alanine, and serine. In some cases, K2includes PASylation of less than PAS100. For example, PAS100 refers to a peptide having 100 amino acids, wherein the amino acids are selected from proline, alanine, and serine. In some cases, K2includes PASylation of less than PAS50. In some cases, K2includes PASylation of less than PAS25. In some cases, K2includes PASylation of more than PAS5. In some cases, K2includes PASylation of more than PAS9. In some cases, K2includes PASylation of more than PAS15. In some cases, K2includes PASylation of PAS5 to PAS25. In some cases, K2includes PASylation of PAS10 to PAS20. In some cases, K2includes PASylation of PAS10. In some cases, K2includes PASylation of PAS20. In some cases, K2includes a beta-alanine that links the PASylation to the drug-linker. In some cases, PASylation is used to extend the plasma half-life. In some cases, PASylation is used to increase solubility. In some cases, PASylation is used to increase solubility without generating secondary structures. In some cases, PASylation issome cases, PASylation is
[0153] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), D is drug unit. In some cases, D includes a spacer. In some cases, the spacer is a divalent moiety that covalently attaches the drug to the linker. In some cases, the spacer is a divalent moiety that covalently attaches the drug to the rest of the molecule. In some cases, D does not include a spacer. In some cases, the spacer can be selected from the group consisting of -Ci-Cio alkylene-, -Ci- Cio heteroalkylene-, -C3-C8carbocyclo-, -O-(Ci C8alkyl)-, -arylene-, -Ci-Cio alkylene-arylene-, -arylene-Ci-Cio alkylene-, -Ci-Cio alkylene-(C3-C8carbocyclo)-, -(C3-C8carbocyclo)-Ci-Cio alkylene-, -C3-C8heterocyclo-, -Ci-Cio alkylene-(C3-C8heterocyclo)-, -(C3- C8heterocyclo)-Ci-Cio alkylene-, -Ci-Cio alkylene-C(=O)-, -Ci-Cio heteroalkylene-C(=O)-, -C3-C8carbocyclo-C(=O)-, -O-(Ci-C8alkyl)-C(=O)-, -arylene-C(=O)-, -Ci-Cio alkylene-arylene-C(=O)-, -arylene-Ci-Cio alkylene-C(=O)-, -Ci- Cio alkylene-(C3-C8carbocyclo)-C(=O)-, -(C3-C8carbocyclo)-Ci-Cio alkylene-C(=O)-, - C3-C8heterocyclo-C(=O)-, -Ci-Cio alkylene-(C3-C8heterocyclo)-C(=O)-, -(C3-C8heterocyclo)-Ci-Ci0alkylene-C(=O)-, -Ci-Cio alkylene-NH-, -Ci-Cio heteroalkylene-NH-, -C3-C8carbocyclo-NH-, -O-(Ci-C8alkyl)-NH-, -arylene-NH-, -Ci-WSGR Docket No. 63125-725.601Cio alkylene- arylene-NH-, -arylene-Ci-Cio alkylene-NH-, -C1-C10 alkylene-(C3-C8carbocyclo)-NH-, - (C3-C8carbocyclo)-Ci-Cio alkylene-NH-, -C3-C8heterocyclo-NH-, -C1-C10 alkylene-(C3-C8heterocyclo)-NH-, -(C3-C8heterocyclo)-Ci-Cio alkylene-NH-, -C1-C10 alkylene-S-, - Ci-Cio heteroalkylene-S -, -C3-C8carbocyclo-S -, -O-(Ci-C8alkyl)-)-S-, -arylene-S-, -Ci- Cio alkylene-arylene-S-, -arylene-Ci-Cio alkylene-S-, -C1-C10 alkylene-(C3- C8carbocyclo)-S-, -(C3-C8carbocyclo)-Ci-Cio alkylene-S-, -C3-C8heterocyclo-S-, -Ci- Cio alkylene-(C3- C8heterocyclo)-S-, -(C3-C8heterocyclo)-Ci-Ci0alkylene-S-, -C1-C10 alkylene-O-C(=O)-, -C3-C8carbocyclo-O-C(=O)-, -O-(C C8alkyl)-O-C(=O)-, -arylene- O-C(=O)-, -Ci-Cwalkylene-arylene-O-C(=O)-, -arylene-Ci-Cio alkylene-O-C(=O)-, -Ci- Cio alkylene-(C3-C8carbocyclo)-O-C(=O)-,-(C3-C8carbocyclo)-Ci-Cio alkylene-O-C(=O)-, -C3-C8heterocyclo-O-C(=O)-, -Ci-Cio alkylene-(C3-C8heterocyclo)-O-C(=O)-, and -(C3-C8heterocyclo)-Ci-Ci0alkylene-O-C(=O)-. In some cases, the spacer can be selected from the group consisting of -C1-C10 alkylene-, and -C1-C10 alkylene-NH-. In some cases, the drug unit is only a drug.
[0154] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A -4), Formula (A-5), or Formula (A-6), D is selected from a Drug unit. In some cases, the Drug unit comprises a drug. In some cases, the Drug unit is a drug. In some cases, the Drug unit is a drug and a spacer. In some cases, D is selected from a drug. In some cases, D is a selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand. In some cases, D is a selected from a cytotoxic agent, and an immune modulatory agent. In some cases, D is selected from exatecan and monomethyl auristatin E (MMAE). In some cases, D is a camptothecin. In some cases, D is exatecan. In some cases, D is. In some cases, D is SN-38. In some cases, D is selected from MMAF and MMAE. In some cases, the cytotoxic agent is selected from the group consisting of an auristatin, a maytansinoid, a camptothecin, a duocarmycin, and a calicheamicin. In some cases, a cytotoxic agent is an agent that has a cytotoxic effect on a cell. In some cases, cytotoxic agents include, for example, tubulin disrupting agents, topoisomerase inhibitors, DNA minor groove binders, and DNA alkylating agents. In some cases, tubulin disrupting agents include, for example, auristatins, dolastatins, tubulysins, colchicines, vinca alkaloids, taxanes,WSGR Docket No. 63125-725.601cryptophycins, maytansinoids, hemiasterlins, as well as other tubulin disrupting agents. In some cases, auristatins are derivatives of the natural product dolastatin 10. In some cases, auristatins are selected from MMAE (N-methylvaline-valine-dolaisoleuine-dolaproine-norephedrine), MMAF (N-methylvaline-valine-dolaisoleuine-dolaproine-phenylalanine) and AFP. In some cases, a cytotoxic agent can be a topoisomerase inhibitor. In some cases, a drug is an immune modulatory agent, such as a TLR7 and / or TLR8 agonist. In some cases, an immune modulatory agent is a STING agonist. In some cases, a drug is a radioactive atom. In some cases, a drug is a proteolysis targeted chimera (PROTAC).
[0155] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), Formula (A -4), Formula (A-5), or Formula (A-6), D is selected from a Drug unit. In some cases, the Drug unit comprises a drug. In some cases, the Drug unit is a drug. In some cases, the Drug unit is a drug and a spacer. In some cases, D is selected from a drug. In some cases, D is a selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and aWSGR Docket No. 63125-725.601. In some cases, D is selected from and. In some cases, D is selected fromWSGR Docket No. 63125-725.601o
[0156] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-2), Formula (A-3), or Formula (A -4), S3is selected from a spacer. In some cases, the spacer is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker. In some cases, S3is present. In some cases, S3is absent. In some cases, the spacer is selected from: alkylene, heteroalkylene (an alkylene having one or more alkylene units replaced by at least one heteroatom selected from Si, N, O and S, with the appropriate valency); poly ether such as poly alkylene glycol and typically polyethylene glycol; one or more natural or non-natural aminoacids such as glycine, alanine, proline, valine, N- methylglycine; C3- C8heterocyclo; C3-C8carbocyclo; arylene, and any combination thereof. In some cases, a spacer is a divalent linear alkylene group. In some cases, the spacer can be selected from the group consisting of -Ci-Cio alkylene-, -Ci-Cio heteroalkylene-, -C3-C8carbocyclo-, -O-(Ci C8alkyl)-, -arylene-, -Ci-Cio alkylene-arylene-, -arylene-Ci-Cio alkylene-, -Ci-Cio alkylene-(C3- C8carbocyclo)-, -(C3-C8carbocyclo)-Ci-Ci0alkylene-, -C3-C8heterocyclo-, -Ci-Cio alkylene-(C3-C8hetero cyclo)-, -(C3-C8heterocyclo)-Ci-Cio alkylene-, -Ci-Cio alkylene-C(=O)-, -Ci-Cio heteroalkylene-C(=O)-, -C3-C8carbocyclo-C(=O)-, -O-(Ci-C8alkyl)-C(=O)-, -arylene-C(=O)-, -Ci-Cio alkylene-arylene-C(=O)-, -arylene-Ci-Cio alkylene-C(=O)-, -Ci- Cio alkylene-(C3-C8carbocyclo)-C(=O)-, -(C3-C8carbocyclo)-Ci-Cio alkylene-C(=O)-, - C3-C8heterocyclo-C(=O)-, -Ci-Cio alkylene-(C3-C8heterocyclo)-C(=O)-, -(C3-C8heterocyclo)-Ci-Ci0alkylene-WSGR Docket No. 63125-725.601C(=0)-, -C1-C10 alkylene-NH-, -C1-C10 heteroalkylene-NH-, -C3-C8carbocyclo-NH-, -O-(Ci-C8alkyl)-NH-, -arylene-NH-, -C1-C10 alkylene- arylene-NH-, -arylene-Ci-Cw alkylene-NH-, -C1-C10 alkylene-(C3-C8carbocyclo)-NH-, - (C3-C8carbocyclo)-Ci-Cio alkylene-NH-, -C3-C8heterocyclo-NH-, -C1-C10 alkylene-(C3- C8heterocyclo)-NH-, -(C3-C8heterocyclo)-Ci-Cio alkylene-NH-, -C1-C10 alkylene-S-, - C1-C10 heteroalkylene-S -, -C3-C8carbocyclo-S -, -O-(Ci-C8alkyl)-)-S -, -arylene-S-, -Ci- Cio alkylene-arylene-S-, -arylene-Ci-Cio alkylene-S-, -Ci-Cio alkylene-(C3- C8carbocyclo)-S-, -(C3-C8carbocyclo)-Ci-Ci0alkylene-S-, -C3-C8heterocyclo-S-, -Ci- Cio alkylene-(C3-C8heterocyclo)-S-, -(C3-C8h etero cyclo) -Ci- Cio alkylene-S-, -Ci-Cwalkylene-O-C(=O)-, -C3-C8carbocyclo-O-C(=O)-, -O-(C C8alkyl)-O-C(=O)-, -arylene- O-C(=O)-, -C1-C10 alkylene-arylene-O-C(=O)-, -arylene-Ci-Cw alkylene-O-C(=O)-, -Ci- Cio alkylene-(C3-C8carbocyclo)-O-C(=O)-,-(C3-C8carbocyclo)-Ci-Ci0alkylene-O-C(=O)-, -C3-C8heterocyclo-O-C(=O)-, -C1-C10 alkylene-(C3-C8heterocyclo)-O-C(=O)-, and -(C3-C8heterocyclo)-Ci-Cio alkylene-O-C(=O)-. In some cases, S3is optionally substituted with one or more of the substituents selected from (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -O-S(O)2R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN; (ii) CUo alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, C3.io carbocycle and 3-to 10-membered heterocycle; and(iii) C3.io carbocycle and 3 -to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6 alkyl, C2-6alkenyl, and C2.6alkynyl. In some cases, S3is optionally substituted with one or more of the substituents selected from (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -O-S(O)2R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, S3is un substituted. In some cases, S3is substituted. In some cases, S3is a phenylene. In some cases,S3 is
[0157] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-3), Formula (A-4), Formula (A-5), or Formula (A-6), S4is selected from (i) an optionally substituted Ci-C3o alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -WSGR Docket No. 63125-725.601N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, — C(0)0—, -S-, — S(0)—, — S(0)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-. In some cases, S4is selected from (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, -C(O)-. In some cases, S4is selected from (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -O-, and -C(O)-. In some cases, S4is selected from: (i) an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, and -C(O)-. In some cases, S4is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, -S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, or -P(O)(R20)2-. In some cases, S4is selected from: (i) an optionally substituted C6-Ci0alkylene wherein one or more alkylene units of the C6-Ci0alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-. In some cases, S4is an optionally substituted Ci alkylene. In some cases, S4is an optionally substituted C2alkylene. In some cases, S4is an optionally substituted C3alkylene. In some cases, S4is an optionally substituted C4alkylene. In some cases, S4is an optionally substituted C5alkylene. In some cases, S4is an optionally substituted C6alkylene. In some cases, S4is an optionally substituted C7alkylene. In some cases, S4is an optionally substituted C8alkylene. In some cases, S4is an optionally substituted C9alkylene. In some cases, S4is an optionally substituted C10 alkylene. In some cases, S4is an optionally substituted Cn alkylene. In some cases, S4is an optionally substituted Ci2alkylene. In some cases, S4is an optionally substituted C13 alkylene. In some cases, S4is an optionally substituted Ci4alkylene. In some cases, S4is an optionally substituted Ci5alkylene. In some cases, S4is an optionally substituted Ci6alkylene. In some cases, S4is an optionally substituted C17 alkylene. In some cases, S4is an optionally substituted Ci8alkylene. In some cases, S4is an optionally substituted C 19 alkylene. In some cases, S4is an optionally substituted C20alkylene. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, -S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, or -P(O)(R20)2-. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by -N(R20)-. In some cases, the one or more alkylene units of the alkylene of S4are optionallyWSGR Docket No. 63125-725.601and independently replaced by -N(R20)C(O)-. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by -C(O)N(R20)-. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by — C(O)~. In some cases, the one or more alkylene units of the alkylene of S4are optionally and independently replaced by -O-. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S4are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S4are replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene unit has no -N-N- or -O-O-. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of S4are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resulting alkylene has only 1 heteroatom. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 4 heteroatoms, wherein the 4 heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 2 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 3 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 5 replaced units. In some cases, the optional substituents on S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN; (ii) CMO alkyl, C2. io alkenyl, C2-io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle. In some cases, the optional substituents on S4, are independentlyWSGR Docket No. 63125-725.601selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN. In some cases, the optional substituents on S4, are independently selected at each occurrence from: halogen, -OR30, -N(R30)2, =0, and -CN. In some cases, the optional substituents on S4, are independentlyselected at each occurrence from: =0. In some cases, S4is selected fromcases, S4is
[0158] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), Formula (A -4), or Formula (A-7), M2is a connector unit. In some cases, the connector unit refers to a component that connects different parts of the conjugate together. In some cases, the connector unit can connect the Targeting Unit to S3(if present) or to S2. In some cases, the connector unit forms a bond with a sulfur atom of a Targeting unit. In some cases, the connector unit forms a bond with a sulfur atom of a Targeting unit via a maleimide group. In some cases, the sulfur atom can be derived from, for example, a sulfhydryl group of a Targetingunit (e.g., a thiol group of an interchain disulfide bond). In some cases,M2is °. Incases, M2is -CH2-C(0)NH-. In some cases, M2is linked to the Targeting unit via a disulfide bond between a sulfur atom of M2and a sulfur atom of the Targeting unit. In some cases, M2is |_s— I1 •. In some cases, the connector unit forms a bond with a primary or secondary aminoWSGR Docket No. 63125-725.601OHgroup of a Targeting unit. In some cases, M2is selected from, and O OH OH. In some cases, M2is. In some cases, M2isOH
[0159] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XXI), Formula (XXII), Formula (XXIII), Formula (A), Formula (Aa), Formula (Ab), Formula (A-l), Formula (A-3), Formula (A -4), or Formula (A-7), the Targeting unit is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, L is an anti-5T4 antibody. In some cases, the 5T4 antibody is modified with a group capable of reacting to form M2(e.g., to form, N„N 'N N" NN N). In some cases, the PTK7 antibody is modified with a, N„ N 'N N" NN Ngroup capable of a click reaction to form M2(e.g., to form)•
[0160] In some embodiments, a conjugate of Formula (A), is represented by:WSGR Docket No. 63125-725.601DAR L is an anti-5T4 antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, L is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, 5T4 is selected from an antibody from Table 5. In some cases, the 5T4 antibody comprises a sequence described elsewhere herein.
[0161] In some embodiments, a conjugate of Formula (A), is represented by:DAR L is ananti-5T4 antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, L is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, 5T4 is selected from an antibody from Table 5. In some cases, the 5T4 antibody comprises a sequence described elsewhere herein.
[0162] In some embodiments, a conjugate of Formula (A), is represented by:WSGR Docket No. 63125-725.601DAR L isan anti-5T4 antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, L is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, 5T4 is selected from an antibody from Table 5. In some cases, the 5T4 antibody comprises a sequence described elsewhere herein.
[0163] In some embodiments, a conjugate of Formula (A), is represented by:DAR L is ananti-5T4 antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, L is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, 5T4 is selected from an antibody from Table 5. In some cases, the 5T4 antibody comprises a sequence described elsewhere herein.
[0164] In some embodiments, a conjugate of Formula (A), is represented by:WSGR Docket No. 63125-725.601DAR L isan anti-5T4 antibody or an antigen-binding portion thereof, wherein the antibody or portion thereof optionally without the C-terminal lysine, K1is as described elsewhere herein, and DAR is selected from about 1 to about 8. In some cases, L is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the DAR is about 8. In some cases, the DAR is as described elsewhere herein. In some cases, 5T4 is selected from an antibody from Table 5. In some cases, the 5T4 antibody comprises a sequence described elsewhere herein.
[0165] In some embodiments, a conjugate of Formula (A), is represented by:WSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601Conjugateso.oDARDARWSGR Docket No. 63125-725.601Conjugateso | o | o | o | o ^'N^YN'^Nx^fN'^N^YN^N^YN-^N^Y°HWSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601ConjugatesDARWSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601wherein each DAR is independently from about 1 to about 8. In some cases, the DAR is from about 2 to about 8. In some cases, the DAR is about 2. In some cases, the DAR is about 3. In some cases, the DAR is about 4. In some cases, the DAR is about 5. In some cases, the DAR is about 6. In some cases, the DAR is about 7. In some cases, the DAR is about 8. In some cases, L is a Targeting Unit, wherein the Targeting Unit is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the antibody is selected from Table 5.
[0166] In some embodiments, a conjugate of Formula (A), is represented by:WSGR Docket No. 63125-725.601Conjugates0°L- - -SAN'^ANH0.x>HNA'^'NH0, 6 k-N^N^N^N^N^N^¥N^AN^¥N^A0H1NH0HoHoHoH0 OTXF'^'N^k K\ 1.v HO<Z°oD AR 5 0 OL— - AN^^NH1CL%HN^YHI > AH0 UV O^NH H o H 9 H? H? H O / v yka n n n "h- ^UJCN-?k. / °HOTA X O > J )AR 5 0 0L- - -, AN^'^'NH(X%0 Ho O^N^ i o | 9 i 9 i 91?OYO <tfN^N^'N^'N^tfN^“'N^rN^'N^rNv / kOH _^\. NH 010101010 XZ X? N^°VH0AL / °\ 0D AR5WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601ConjugatesDARDARWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601ConjugatesDARDARooWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601Conjugates^DARDARWSGR Docket No. 63125-725.601Conjugateso 1 0 H O I OHONH O O O 0_ L 7 - ‘v- — - A oHo kA^-N'O^NY^-NY0, 0H0 o< NHAAoHO\ o J DAR 5 O 1 O H ° 1 0 H °A p N N^ ]fNA^KN, AA_ ]] N^A. N|AA ]f, N^A. N|AA ]]. N^A. NIUH2NH O O O O- L O H °Y^ - OH0 CVN<- „0 / Qz,. N / , N / 0^0Ho o'NHF'^'N'A\ AAA°vHO<° y DAR 5HO\ A A'fCaV"o ^^0O 7 H o °yNHH0* °YYfNY^NA^°H) NH 01 Hk OBkAHOaXNA O ^. Q^N “y^ °^NyA^OyOHO 0■NHF^-^N^k yA_ / °VH0< 0DAR 5WSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601wherein each DAR is independently from about 1 to about 8. In some cases, the DAR is from about 2 to about 8. In some cases, the DAR is about 2. In some cases, the DAR is about 3. In some cases, the DAR is about 4. In some cases, the DAR is about 5. In some cases, the DAR is about 6. In some cases, the DAR is about 7. In some cases, the DAR is about 8. In some cases, L is a Targeting Unit, wherein the Targeting Unit is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the antibody is selected from Table 5.
[0167] In some embodiments, a conjugate of Formula (A), is represented by:WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601Conjugates0 oL- - - AN^^NHCk%tYN- X\IU HN^YHI0 H 0O^NHH9 H 9 H 9 H 9 H 9 / OVOLYN^N^trN^tN-YN^kN^irN^^N^kNH2^.. NH 0H0HOHOH0F nt hHOT k. A / ° Jt )AR 5-0°L -0°>%, o, 0, 0, 0, o OVO AN^N^N^N^N^N^YN^AN^fNY<oH O 010101O o xwF Nt h\ HO* 1W. z°\ 0c )AR 5L _<0^N'^A0-NHA0°h^0rhhaotNrX, o, =, -, o, oOvo ANh^NYrNh^N^Nh^N^N'~ / U'N'^n'N'^XNH2 / x -NH 0 0101010 Tx xw\ p" Ao t )AR 5WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601ConjugatesLA sAL A DAR 5.- A S )Y" AV iV^N^N^N^N^N^N^N^OH'XXXN'^LHC / HODAR.- A °? A - A s °> %V Z A AHJ A."NH°Y°XXX / A<Ht9A JJAR 9.WSGR Docket No. 63125-725.601ConjugatesooDARo.oDARDARWSGR Docket No. 63125-725.601ConjugatesDARDARWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601Conjugates0 I 0 I 0 I O I o_. O N1O1O101010A - OV A NHV 0 A YA / - -NAA O / ozH OVA— - - L, N. ZZN Z / O OH0 o> ZA'^HAAQ^I\ OHOVoDAR 50 1 0 1 0 I 0 0_. O N ^NA 0N^NA 0N^NA 0N^NA 0N^NA 0NH2- L Y O AAHY O A Zr'Nz XZO,z Q- Z " N Z V. N / — —O OH0 o, Z, NHF'^'-AAy AA_0VH\ O y DAR 59 H 9 t! 9H? H OhA0 HVHAN^NAN^N° °HAN^N°HAN^N°HA°OHL V / NW oHO AHo z>' / Nz zO / ff- zN / . N / O OH0 oA'NHF^A'A AIApLHo\o J DAR 5? H0H 0 H 0 AAN^NAN^NAN^NAN^NAH O H °YNH 0°H°H°H0NH2- L ^'AVYS o H °Y^ — ' - o AHo Z-NAOz^Q^Ny^NY^O^zOHO oA, NHF ^'^V^ANAA^^AtA pH°VoDAR 5WSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601ConjugatesDARDARWSGR Docket No. 63125-725.601 ConjugatesWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601ConjugatesDARWSGR Docket No. 63125-725.601WSGR Docket No. 63125-725.601wherein each DAR is independently from about 1 to about 8. In some cases, the DAR is from about 2 to about 8. In some cases, the DAR is about 2. In some cases, the DAR is about 3. In some cases, the DAR is about 4. In some cases, the DAR is about 5. In some cases, the DAR is about 6. In some cases, the DAR is about 7. In some cases, the DAR is about 8. In some cases, L is a Targeting Unit, wherein the Targeting Unit is an anti-5T4 antibody or an antigen-binding portion thereof. In some cases, the antibody is selected from Table 5.Table A: Specific Conjugates of the DisclosureConjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL 9) L is 5T4-7EL 10) L is 5T4-8EL 11)L is 5T4-9; 12)L is 5T4- 9EL;13)L is 5T4- 10EL;14)L is 5T4- 11 EL;15)L is 5T4- 12EL;16)L is 5T4- 13 EL;17)L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18)L is 5T4- 15EL;19)L is 5T4-16; 20)L is 5T4-17; 21)L is 5T4-18; 22)L is 5T4-19; 23)L is 5T4-20;or24)L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- ^ VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; ' K-NHCQ [H0^7\AOH 11) L is 5T4-9; YYVW rt (£ 12) L is 5T4-9EL;ACHNVt1 13) L is 5T4- ' y 10EL;DAR14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; tr22) L is 5T4-19; 5 > r Q23) L is 5T4-20; IZ ZZ orIZ$ °= 24) L is 5T4-21. rzz 1) L is 5T4-1EL; zz>^ °2) L is 5T4-2EL; rzz 3) L is 5T4-3EL; zz4) L is 5T4-3EL- zz r5 ° VL;zzz z > OO= 5) L is 5T4-4EL;r^or / 6) L is 5T4-5EL; 4O <' °z Ot o=7) L is 5T4-5EL- 1°L- ^, y{°==Vo:VH;zz / K O= 8) L is 5T4-6EL; zz '_ _? k )°= 9) L is 5T4-7EL;10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- 0 0 VH;L- - - __Ck 8) L is 5T4-6EL;% 9) L is 5T4-7EL;11 O I H OYN'TXN'SrN'C] HN^-'NHL 10)L is 5T4-8EL; o A.H0 ANHHO H 0 H o H 0 H ° AOVO OA AANAANAAA -A 11) L is 5T4-9; AH0H0H°H°012)L is 5T4-9EL; XA AM013) L is 5T4- HO-A JDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;ro 0 7) L is 5T4-5EL- L- — _<AN^^“'NHVH;A8) L is 5T4-6EL;%9) L is 5T4-7EL; -<, 0 o, 0, 0, « >OyO ^N^N^fN^'N^['N^N^fN^'N^l'N^OH 10)L is 5T4-8EL;01O10101O11) L is 5T4-9; YXXDM012)L is 5T4-9EL;I / OH0Vo J 13) L is 5T4- DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;r7) L is 5T4-5EL- 0 OL- _ AN^^'NH VH;o. 8) L is 5T4-6EL;%H 0 I H 0 9) L is 5T4-7EL;-< 10)L is 5T4-Y trN, j?.? a r 8EL; o o < ^“'N^rN^'N^fN^'N^rN^“'N^r ^NH2 / \.. NH 010101010 11) L is 5T4-9;U YW 12)L is 5T4-9EL; \ A! / HO'XA0_z_.. _ 13) L is 5T4- DAR10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- 0 0- - (AN''' NH VH; L0% 8) L is 5T4-6EL;^0H o i H 9 \ 9) L is 5T4-7EL;V- N 'N• HN^'NH>0 H 0O NH I 0 1 0 1 0 1 0 1 9 10)L is 5T4-8EL;o o CN^N^N^N^N^N^N^N^N^ANH2. NH 0 H 0HoHOH0 11) L is 5T4-9; nYM° 12)L is 5T4-9EL;V k. / ° J HO-W 13) L is 5T4-0DAR10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- — A S 7 VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;Y / YHNI ^T'O:5 NNHH) y ‘Y AyAy Ay AyA 10)L is 5T4-8EL;11) L is 5T4-9; F^-^N-^ ZY 12)L is 5T4-9EL;H° / 413) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- - A s 1 VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; XXSA-Y 12)L is 5T4-9EL;L n J13) L is 5T4- DAR10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;S8) L is 5T4-6EL; 9) L is 5T4-7EL;A nHNI ^TH>10)L is 5T4-8EL; T11) L is 5T4-9; F 12)L is 5T4-9EL;V J DAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; o o " AL~ - - 7) L is 5T4-5EL- S VH;%8) L is 5T4-6EL; u 0 i H o ^7^vALvy AYH9) L is 5T4-7EL; y ° / SH 0O’SIH o.hAA oYo CANA^N^-OH / \., NHH0N>=O 10)L is 5T4-8EL; SXQWO 11) L is 5T4-9;° -H°OSHY P 9 1 H o 12)L is 5T4-9EL;HOvo O' nN / 0HHO713) L is 5T4- 10EL;DAR14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 0 0 A 7) L is 5T4-5EL- L VH;0AL HOH / 8) L is 5T4-6EL; I_I n o i H O 9 ^ i °1o b'^N- HN^YNHHN / / ° 9) L is 5T4-7EL; °H 0 / OAH o.hHNA y°Y° N XN X 0HX™ ( 10)L is 5T4-8EL; 'NH H°AN H 0.nGyo11) L is 5T4-9; n rN? y / ti s i AHVU\\ 00"• T■ L Ton0o\. LvN>HOHN. O 12)L is 5T4-9EL;HOVO 0 PH0VNSH° ) Lv ^ 13) L is 5T4- DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; o o ■'x 7) L is 5T4-5EL- L— _ AN^AIHVH;l0H2N H 8) L is 5T4-6EL; „ 0, „ 0 S'0° 1?' V9) L is 5T4-7EL; v o A AHV o TIH’JI'' JOANIHH O.H° A HN'H I°Y° 0*'NA< N'<'OH r-A° A 10)L is 5T4-8EL; n-'NH H°rNH o i r\ CM ( 11) L is 5T4-9;0 - H o0A-NH X. N\ n.Wjb Af° o° X? oHAo 12)L is 5T4-9EL; Ao O 'AVo 13) L is 5T4- HO10EL;DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- HNNNNNNH VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;J \ V 10)L is 5T4-8EL;11) L is 5T4-9; AN^N^N^N^N^N^N^N^N'-ADH12)L is 5T4-9EL;O K 13) L is 5T4- V J DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;N = N TCSSSXlw o 7) L is 5T4-5EL- o VH;Ck8) L is 5T4-6EL;1 0. 9) L is 5T4-7EL;1 H 0 | H 0 I'y 10)L is 5T4-8EL;HN^>-‘NH0 H 0fo^hT I o i o | o | o i o 11) L is 5T4-9;OyO <^N^N^N^N^N^N^N^U'NX>['N'-ZU'’OH^\. NH 010101010 12)L is 5T4-9EL; xxxw 13) L is 5T4- th\ PHOVo J 10EL;DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;L07) L is 5T4-5EL- VH;0S CX8) L is 5T4-6EL;^01 0 9) L is 5T4-7EL;10)L is 5T4-8EL; 1 H 0 i H 9HN^-NHf 11) L is 5T4-9;0-XH 0CAA o'N' I o i o i o i o i oo oLVN^N^N^N^N^N^N^N^N^AOH / ^. NH 0 0101010 12)L is 5T4-9EL; O XW 13) L is 5T4- \ L010EL;HO' o JDAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;L— ° O AN N H 8) L is 5T4-6EL;^^^^0 S°>L^ L 9) L is 5T4-7EL;0 / H0! H 9 ' ° 10)L is 5T4-8EL; -4YN- / N\NY^ HN^ 'NHI0 / kHo k^kk o ' N I 0 1 0 1 0 1 9 9 (o, o ^N^N^N^N^N^N^N^AN^¥N^A0H11) L is 5T4-9; / ^. NH 0 010101012)L is 5T4-9EL; li xW13) L is 5T4- \ HO< ' z° y 10EL;DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;\ 9) L is 5T4-7EL;10)L is 5T4-8EL; < V I11) L is 5T4-9; AMNnHMH12)L is 5T4-9EL;, NHy 13) L is 5T4- I HOT\ 10EL;V J DAR14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;H 0 i H 9 0 9) L is 5T4-7EL; JV< ON'IXI1'N" TAYYA H 0 9 H H - I 10)L is 5T4-8EL;I °y°H| 0 | 0 | 0 1 0 I 0 (Y>'NH LYN'A'N^YN'A-N^YN^.N^irN^.N^YN^k0H11) L is 5T4-9;n 010101010IT TWF NY A 12)L is 5T4-9EL;YL0HOVo J 13) L is 5T4- DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;^-L 8) L is 5T4-6EL;9) L is 5T4-7EL;H O i H 9 00 ^NH H > 10)L is 5T4-8EL;°Y°HCT N' I 0 I 0 I 0 I 0 I 0 11) L is 5T4-9;O'NHYN^'N^|fN^'N^|fN^U'N^fN^U'N^fN^'NH2xJA n 010101010TYT'M 12)L is 5T4-9EL; F NAA-,< HO-HOJ 13) L is 5T4- DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;H 0 i H 9 0 9) L is 5T4-7EL;J S X " 5 110)L is 5T4-8EL;] °V°HO^NH u O H ° H 9 H 9 H 9 XxAXn0HOH0H0H0 11) L is 5T4-9; ITTW VJ-A 12)L is 5T4-9EL;P HO^ J13) L is 5T4- DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; H01 H 9 p-<\ 'YN' / 'N\N'TPN 0 < 10)L is 5T4-8EL; ] 0 AH6 UVN^'TNH H(°v°H0^~NHHOHO H 9 H 9 H 9 11) L is 5T4-9; rx™ n in nnhi12)L is 5T4-9EL; W K13) L is 5T4-HOVoJDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;° 0 7) L is 5T4-5EL- L - _ AN'^^NH VH;8) L is 5T4-6EL;X) 9) L is 5T4-7EL;H °! H 0 V° I 10)L is 5T4-8EL; Y / NW J N HN^O1'NNHH O>11) L is 5T4-9; 12)L is 5T4-9EL;^. NH H O'0H13) L is 5T4- 10EL;V_ o JH°Vo DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;L8) L is 5T4-6EL; 9) L is 5T4-7EL;0 / kHO O^NH 1 O 1 0 1 0 1 0 1 Q > 10)L is 5T4-8EL;oYolYN^N^trN^'N^rN^N^IrN^'N^irN^oH<OH0H0HOH0 11) L is 5T4-9;2o xW 12)L is 5T4-9EL;F Nth\,o< H0*W 13) L is 5T4- \ ° _yDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- z ° 0 VH;L^0 S 8) L is 5T4-6EL;u 9) L is 5T4-7EL; I_I 0 ■ H OV-A N HN^'NHy 10)L is 5T4-8EL;0 H° O NH I 0 1 o 1 O 1 0 1,? |0,0 yN^N^N^N^N^N^YN^AN^fN^ANH211) L is 5T4-9;, NH 0H0H0HOHO12)L is 5T4-9EL; Xy5y^°V ^y^z o y 13) L is 5T4-HO\ o DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-0o VH;L_ - 0 S 8) L is 5T4-6EL;% 9) L is 5T4-7EL; JY / AYN AY L 10)L is 5T4-8EL;° W o\H |0H0, 0, 0Ho rOyO <|rN^N^N^N-YN-AN-VN-AN-YN'A> H 11) L is 5T4-9;01010H01012)L is 5T4-9EL;J°AR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- A ° o VH;. AN^^NH8) L is 5T4-6EL;^-^0 S 0.9) L is 5T4-7EL;%J H0I H 0 10)L is 5T4-8EL;5vN' AVrN HN^^ 'o AHo LA JNHO A f^NH | 0H0 | 0 | 0HO0. 0 k N A / \ N A ^-\ N A / \ N A x\ N A 11) L is 5T4-9;UY \N^NAT ^NAf ^NH2 / \ 'NH 01010H010 12)L is 5T4-9EL; 'XXX>^1 JF N^A> 13) L is 5T4- DARH°A° 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; XN^N^N^N^N^N^N^N^OH11) L is 5T4-9;12)L is 5T4-9EL;Xx X13) L is 5T4- p -" DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;- S 8) L is 5T4-6EL;9) L is 5T4-7EL; 10)L is 5T4-8EL;AW cv^:11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- P7 yDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; a:< 22) L is 5T4-19; _ _ A Q23) L is 5T4-20; OA o f'iz o or^o1^ZI 24) L is 5T4-21. J vzs O O#z T 1) L is 5T4-1EL; < zQA> 2) L is 5T4-2EL;3) L is 5T4-3EL; 4) L is 5T4-3EL- AC VL;ZTv5: x ■ 5) L is 5T4-4EL;6) L is 5T4-5EL;r4O oyC rr °°°°7) L is 5T4-5EL- RLJrx° °L— V TZ vM °HVH; / AZT 8) L is 5T4-6EL; / K °Z I 9) L is 5T4-7EL; _ _ J A°10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; r 7) L is 5T4-5EL- ° oVH;L - O 1O8) L is 5T4-6EL; x>H 0 I H 91''7>9) L is 5T4-7EL; < VA\VN HN^VNH11 0Ho " O^NH O.H10)L is 5T4-8EL;o, o CJ^^JA -NY^OH / 11) L is 5T4-9; rrH°n H? i o° -H° O^NHO12)L is 5T4-9EL; V / ° "■ ' 9 1 H o 13) L is 5T4- 1VHOVo 0ANHV'AHo )2J HO y 10EL;DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- Z ° oL VH;0°> 8) L is 5T4-6EL;LH? H p)U n 0 1 H O < 1 °0^! N'6ff'L'lL ■" 9) L is 5T4-7EL; ^yN- / 'N\NY^N HN^Y'NHHN^°°H 0‘^V O NH 0. H HN'^_H< 10)L is 5T4-8EL;o o ' N #N X 0H, / o <n, NH H on H o,oGro 11) L is 5T4-9; I Y VM0 V'XN'TAH n i AHMNA0TCo O ^NH / . 12)L is 5T4-9EL; \ p "" Y 0 | U OHNOIHOVxo 0 AH0NH) / N LAV 13) L is 5T4- HO yDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;^8) L is 5T4-6EL; Y 9) L is 5T4-7EL;HNA^> -NH< 1 Z A IYCX A A 10)L is 5T4-8EL;Y ( 11) L is 5T4-9;A°YYV ACHN%012)L is 5T4-9EL;A / H < 13) L is 5T4- V H^AAOH 10EL;j' DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;oO^N.1O 8) L is 5T4-6EL;9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;O | O 1 O | O 1 op N Y N Y N Y N Y N Y * 8) L is 5T4-6EL;O N O O O O OH 9 I H | _ _ L 9) L is 5T4-7EL; uM Y 0 H — ■ — —J o AH0 UY 'NA^°^o^NyA y ’ V 10)L is 5T4-8EL;A 0, 0HO 0 A, NH 11) L is 5T4-9; F^ UXNXAYUN^L 12)L is 5T4-9EL;HP 13) L is 5T4- Lv\ 0yJnA nDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; _AQ\ ( ) X 23) L is 5T4-20; or° orZI24) L is 5T4-21. r° 1) L is 5T4-1EL; ZI2) L is 5T4-2EL; y xz r Xoorho° 3) L is 5T4-3EL; > IZ 4) L is 5T4-3EL- > xzr o ° VL;<ziJ 5) L is 5T4-4EL; Vv < P<x °*° 6) L is 5T4-5EL; ( z J zxo7) L is 5T4-5EL- ) xz c —x v1VH;^ z>'OZX 8) L is 5T4-6EL; X / °IZ \ 9) L is 5T4-7EL; _ c J10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;9H9 H ° H OHo 8) L is 5T4-6EL;A^N^N^N^N^N^N^fN^N^rNH2H0. H°YNH° °H°H°H° L 9) L is 5T4-7EL;N' A N ' -N0 H 'yO / HO ^ / N- zO / O... N. / , N / i 10)L is 5T4-8EL;A 0, 0Ho o YCY 'NH 11) L is 5T4-9;12)L is 5T4-9EL;\ 9 13) L is 5T4-V x JDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH; t! °«'0Hr Y ° o_ o^NH 0 8) L is 5T4-6EL; H 9 I H 1TNYS o H 9) L is 5T4-7EL; 1 o AHo YV^LV o^oHo o > 10)L is 5T4-8EL; | O 'NH11) L is 5T4-9;12)L is 5T4-9EL; 13) L is 5T4- 10EL;H0Vo )< DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;9Hi? H OHoH08) L is 5T4-6EL; H? I H°YNH’0 1° ’ J1°1O 9) L is 5T4-7EL; V' / NVA o H Vv^- - - 1 O AHO 1OyOHO 0 V 10)L is 5T4-8EL;O ’l^H 11) L is 5T4-9;12)L is 5T4-9EL;A,zo1 “°A J 13) L is 5T4- DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- C" O | O | 0 H O | O VH;ZN N N N N0NH10HO1O10HO 8) L is 5T4-6EL;H 9 iHY „.N” X N 'N, o H Y-^ - - - - 9) L is 5T4-7EL; J O OH0 o k 10)L is 5T4-8EL; ) O'^H111) L is 5T4-9; 12)L is 5T4-9EL;\ oHO\ o 13) L is 5T4-v JDAR10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- 0 | 0 | 0 H o | o " A VH;-^ N N N N N *oNH OHO O OHO 8) L is 5T4-6EL;H 0 iHYYA 9) L is 5T4-7EL; o YA oAHo AA^NA^O^O^ HN¥^ °YNYA^—^ — — ■ —j 0, 0 H o 0 I 10)L is 5T4-8EL;A <nhA11) L is 5T4-9; XEQ412)L is 5T4-9EL; A_J°HO' o 13) L is 5T4-V JDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- C VH;9 9H9 9H98) L is 5T4-6EL; NH1O 0 O 09) L is 5T4-7EL; Ap / X o „ - —J o H o IL10)L is 5T4-8EL; A. o, oHo o A, NH 11) L is 5T4-9; XXXNA? 12)L is 5T4-9EL;13) L is 5T4- LHO<° Jv yDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;p N y N n N n N n NH28) L is 5T4-6EL;NH O 0 0 0H n 9 iH° 1 / _ _ LV / NVYS 9) L is 5T4-7EL;O H\ OH0 LA ^o- _N. y- ’ 1A 0, 0HO 0 V 10)L is 5T4-8EL;y\, NH 11) L is 5T4-9; XTXN^L 12)L is 5T4-9EL;1H°Vo 1 13) L is 5T4-vDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;_ _ \23) L is 5T4-20; or\24) L is 5T4-21.\$\ 1) L is 5T4-1EL;2) L is 5T4-2EL; 3) L is 5T4-3EL;V4) L is 5T4-3EL- V VL;0 5) L is 5T4-4EL; r\t ==7 o6) L is 5T4-5EL; rv 7) L is 5T4-5EL- ynV^- y V VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;_ _ V J10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;,H0\ "x 7) L is 5T4-5EL- r W o A1 HY ° A VH;n ' 0o = H O °, NH8) L is 5T4-6EL;H oyv5 ° ‘ ° 9) L is 5T4-7EL;NH O *HH 0 1 H ° Y y 10)L is 5T4-8EL;o H YA _ (oHo;Z- y-NA^o. - Q' -N Z, N. / - 11) L is 5T4-9;0, 0H0 oL, NH 12)L is 5T4-9EL;13) L is 5T4- HO*M ) 10EL;x-^ DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL; cHO>°VNA P OHNHu5) L is 5T4-4EL; C >- H< N— <H 2NA 6) L is 5T4-5EL;. NHO 7) L is 5T4-5EL- O^NH^5=0VH;°KN ) CA<°OH8) L is 5T4-6EL;>NHoHN>-o9) L is 5T4-7EL; 10)L is 5T4-8EL;HIM -6 yNzHVJ Z 11) L is 5T4-9;) Zo °ANH12)L is 5T4-9EL; r, OV7H 9 I H 1V-A-VYS oHVv— — — —l13) L is 5T4- o A.Ho LA Y- H^0-O'.'NY0^0H0 0 10EL;O'NH14) L is 5T4- 11 EL; XXXN^l15) L is 5T4- IHOVo J 12EL; DAR16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;ZNH OHN 6) L is 5T4-5EL; HN ( / •>? 'L >-■■< 'A HNA.N Oo / \ ° 7) L is 5T4-5EL-. / o NHOVH;O zNHAo0 \FN | 8) L is 5T4-6EL;HN— < HN».Q A ' L>NHoHk ° 9) L is 5T4-7EL; y A _ \ ° y0kjHn —. \.- 0 Q N 10)L is 5T4-8EL; \HN( YNH AASXO=< 11) L is 5T4-9;(NH° NH212)L is 5T4-9EL;H? 1H1 r>v-AVA oH°y _ - L 13) L is 5T4- O^OH0 o 10EL;>NH14) L is 5T4- Xy X / A 11 EL;AL °HO\ O y 15) L is 5T4- DAR 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- r0HVH;HO8) L is 5T4-6EL;H^O ^NH°HMOUAc\HNHO ACHNHN^° 9) L is 5T4-7EL;H o I H ° y / 10)L is 5T4-8EL;J Y' MM oHr11) L is 5T4-9;O<^OH0 0 / x^NH 12)L is 5T4-9EL;13) L is 5T4- XXICA3 -0 1 10EL;LH°'C°JDAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; ° u 6) L is 5T4-5EL; L — _ Z'N'^ANH7) L is 5T4-5EL- 0.VH;H 0 1H0 S*08) L is 5T4-6EL; V' AVn HN^ '™ 9) L is 5T4-7EL; o A " o V / O1NH O0-°N' ''°snn U. 10)L is 5T4-8EL; X > NXHO' °H>11) L is 5T4-9; tr" NHy~yO 12)L is 5T4-9EL; 1 zNyV13) L is 5T4- o’U1 AO NU 10EL;'OH-U° 14) L is 5T4- U HO JDAR11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL;1 °? 2) L is 5T4-2EL;L^0 S 3) L is 5T4-3EL;0.SD 4) L is 5T4-3EL- H o! H o A0VL;'YN' A\N1Y HN^ '™oUAhoUJ. 5) L is 5T4-4EL;CF NH o6) L is 5T4-5EL;A. C H 6OHV7) L is 5T4-5EL- tr 'NH \VH;8) L is 5T4-6EL;0]1O^NA 9) L is 5T4-7EL;10)L is 5T4-8EL;A o 11) L is 5T4-9;\v H0y / DAR 12)L is 5T4-9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL;0 0'AL—^0 S 2) L is 5T4-2EL;Ch% 3) L is 5T4-3EL;H 0 i H 0 4) L is 5T4-3EL- W Y T VL; / k 'N,. o H oH0H0HO 5) L is 5T4-4EL;O NH^<.06) L is 5T4-5EL;Y 7) L is 5T4-5EL- O N'^5°. VH; / N^ / 7HHO " 8) L is 5T4-6EL;DAR9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;°?1 L _ _ AN^^NH 7) L is 5T4-5EL- ^0 So. VH;uH0I H08) L is 5T4-6EL;AW-ort " 9) L is 5T4-7EL;i °Y° J ^^NH2Ay*k (5 H oH0H0Ho 10)L is 5T4-8EL;O NH |,, ',;o 11) L is 5T4-9;12)L is 5T4-9EL;0]O ' N 13) L is 5T4- 10EL;<Hh° J 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; c °? 7) L is 5T4-5EL- L— _ _ y^N^^NHS 0. VH;^0 8) L is 5T4-6EL;H 9 | H 0 ■'°YN' AY'A HN^ 'oA" o IA / XNH„o,H9) L is 5T4-7EL; °Y° A. W 10)L is 5T4-8EL;,. Nh0 „>0” „ I >OANHV¥N^N\NY 11) L is 5T4-9; 'Y^Y° ■ 0 =H0Q7 NH12)L is 5T4-9EL;'' o °«YAO N HO 13) L is 5T4- v NA •' _ A ) 10EL;Hnd "DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10)L is 5T4-8EL; 11) L is 5T4-9; 12)L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.
[0168] In alternative embodiments, the specific conjugates of Table A are also envisioned with no stereochemistry defined.Table A-R: Specific Conjugates of the DisclosureConjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;L^°> 6) L is 5T4-5EL;L7) L is 5T4-5EL- J0Y\0VVH;\ 1 V 8) L is 5T4-6EL; VVV^ z°9) L is 5T4-7EL; <~\ z010) L is 5T4- j 8EL;y DAR11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4-x_ _ < A§ r 12EL;Q16) L is 5T4- r 13 EL;17) L is 5T4- r14EL;)o^18) L is 5T4- r°15EL;r° 19) L is 5T4-16;20) L is 5T4-17; 21) L is 5T4-18;VP4 22) L is 5T4-19; 3 M 23) L is 5T4-20;1V ° or / 24) L is 5T4-21. _ _ A < J° 1) L is 5T4-1EL;2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- L VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;ro 0 -XL- - AN^^NH 4) L is 5T4-3EL- ^^0 SCL VL;^0H 0 ■ H 9 '''T 5) L is 5T4-4EL; -< ^0N,HHN^- A. °NHLoSlH H O H 9 H o H O H O < 6) L is 5T4-5EL;°Y° A_ _ 0HOH0H0H0 7) L is 5T4-5EL- AXXW VH;HO-H J 8) L is 5T4-6EL;DAR9) L is 5T4-7EL; 10) L is 5T4- 8EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL;001 1— ~ - 2) L is 5T4-2EL;S0^ 3) L is 5T4-3EL;% 4) L is 5T4-3EL- H O i H 9V'n' -nHN;NHV VL;°H 0o^hT i o i o i o i o J,? <0,0 \'N^N^N^N^N^N^N^N^N''-'AOH / ^. NH O O101O10 5) L is 5T4-4EL;6) L is 5T4-5EL;1TXWF Nt hy 0 7) L is 5T4-5EL- HO-H JDAR VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL;° o A1 L _ AN^^NH 2) L is 5T4-2EL;^0 S3) L is 5T4-3EL;%H 0 i H 9 4) L is 5T4-3EL- A n HN^ -NHyo / CHo CA-A o^'N'' 1 0 1 0 1 0 1 0 I o ( VL;o. o \-N^N^N^N^N^AN'^Y'N'-AN'^YN'^'NH2 / ^. NH 0 01O1010 5) L is 5T4-4EL; Vy xW 6) L is 5T4-5EL;F NI h< Y / ° } 7) L is 5T4-5EL- "°<° DARVH;8) L is 5T4-6EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL;10J?L _n, s 3) L is 5T4-3EL;00 1 4) L is 5T4-3EL- H 0 i H 9 / NzzN',NHN^'NHVL;0zAH 0O NH 1 0 1 0 1 0 1 0 1 O0, 0 zN-.. N zN-, N / N-,. N / N-, N / QH5) L is 5T4-4EL; zz, NH oH0HoH0H06) L is 5T4-5EL; xxxw\ p —. — 7) L is 5T4-5EL- H°-HODARVH;WSGR Docket No. 63125-725.601Conjugates Antibody (L)8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- _ _ A VL;I5) L is 5T4-4EL;7 6) L is 5T4-5EL;A 7) L is 5T4-5EL- r VH;A8) L is 5T4-6EL; r9) L is 5T4-7EL;A10) L is 5T4-?8EL;11) L is 5T4-9; rc°^^° "4YO\' ° 12) L is 5T4- 9EL;13) L is 5T4-?10EL;_ J 14) L is 5T4- L 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- DARl utL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- DAR10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 0 0 A 7) L is 5T4-5EL- L- VH; 0.LH? H r\ 8) L is 5T4-6EL; |_i n 0 i H O 9 ^ l °0< KT1 N¥ 0^N ‘...^N' ZN^Ny^ HNA- / >'NHHNM° 9) L is 5T4-7EL; °H 0AA OAH oH HA k0. 0 A^AN^OM / 0 A 10) L is 5T4- n, NH H°cNH o i n w>8EL;TY JTNA "nN‘ H AF^Nvjh oNH0A O'AHMN NHAY.\ p "" A O. A OHNO 11) L is 5T4-9;HOvoNA0NH N"HC> 12) L is 5T4- DAR 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;Z°06) L is 5T4-5EL;L — - CX 7) L is 5T4-5EL- L H2N rA VH;u n 0 | H 0 O ^f ° 1 oyfN. JN\NYA 8) L is 5T4-6EL;°H° < O^NH O.H\ IJ > 9) L is 5T4-7EL; niNH H°n °? i o i 10) L is 5T4- I T ri\ p i 9 i Cy oHNo 8EL;ho<o o " n\ M H oNH) LA 11) L is 5T4-9;HO12) L is 5T4- DAR 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- X VH;\ L 8) L is 5T4-6EL;9) L is 5T4-7EL; 10) L is 5T4- w8EL;V J DAR 11) L is 5T4-9;12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- N=NL —OVL;C >~'NY^ANH0 5) L is 5T4-4EL;0.^0 6) L is 5T4-5EL; / \ \ 7) L is 5T4-5EL- ] H 0 i H 9 [ VH;v- AVn HN^ ~NHo / XHo cr 'N'' | o i o i o i o o 8) L is 5T4-6EL;0. 6 <^N^N^N^N^N^N^N^AN^¥N^A0H^.. NH 0 0101010 9) L is 5T4-7EL; 'IX XM010) L is 5T4- Y oHO\ o J 8EL;DAR 11) L is 5T4-9;12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;L 04) L is 5T4-3EL- VL;0s05) L is 5T4-4EL;X)1 \ 6) L is 5T4-5EL;7) L is 5T4-5EL- 1 H 0! H 9, N.N' N HN^'NHI0 H 0VH;o'' N I 0 1 0 1 0 1 0 1 00, 6 ^N-J^N'^N^N'^N^N'^fN'-AN'~YN'-AOH / ^. NH 0 0101010 8) L is 5T4-6EL;9) L is 5T4-7EL; U Y H°V_ HO-H J 10) L is 5T4- DAR 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; o o A 4) L is 5T4-3EL- VL;1°>L L0 5) L is 5T4-4EL; / H 0 > H 9 6) L is 5T4-5EL;HN;NH1oH° cr 'N'' | o i o i o i o o (0, 6 A'N^N^N'~A'N'^fN'A'N'^YN'A'N'^YN'~^'OH 7) L is 5T4-5EL- ^. NH 0 O101O10VH;ITVNA08) L is 5T4-6EL;\ HO'! z° y 9) L is 5T4-7EL;DAR 10) L is 5T4- 8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;NMNNN4) L is 5T4-3EL- NH H Q VL;X5) L is 5T4-4EL; 6) L is 5T4-5EL; V-XVYN HN^T'NH7) L is 5T4-5EL- °Y° SrN^NXrN^NXT'N'^'N'X'N'^k'N'X'N'^k'°HVH;fX^X"^nXM0X yL~\ 8) L is 5T4-6EL;0V J DAR 9) L is 5T4-7EL;10) L is 5T4- 8EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; __-L 4) L is 5T4-3EL- H O i H 9 0JV' AAX'TC'N 0 VO^^N^NA - VL;< o AhSHL°Y°H, 0 | O | O | O 1 O A 5) L is 5T4-4EL; <vNH lyN^ll'N^i'N^u'N^i'Nx / ll'N^rN^l'N^tTN^" OHvVA o0 1 0 1 0 1 0 1 06) L is 5T4-5EL; XX XNAi XP 7) L is 5T4-5EL-HOVo JVH;DAR8) L is 5T4-6EL; 9) L is 5T4-7EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL;L 3) L is 5T4-3EL; 1 4) L is 5T4-3EL- H o i n 9 pN' YN'TCN9 - oy lHo NH H I > VL;0 0 HoXxI 0 I 0 I 0 I 0 I 0 5) L is 5T4-4EL; X ^X. NH V^N^N^N^N^N^N^N^N^NH20 ° ' ° 0 ' 0 0J I XM 6) L is 5T4-5EL; 1 V 0HO-H J 7) L is 5T4-5EL- DAR VH;8) L is 5T4-6EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; H 0 i H 9 P'YN' ZN\'N'1PN OJ OH0 H 1 4) L is 5T4-3EL- 1 O0-NH0 HO N ^H NH^ 0N^HN^ 9N^ HN^9N^ HN^A 9N^YHN^A °OHA VL;X I n 0Ho H o H oH01 1 TM 5) L is 5T4-4EL;06) L is 5T4-5EL;HOVo J7) L is 5T4-5EL- DAR VH;WSGR Docket No. 63125-725.601Conjugates Antibody (L)8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;J H o I H 9 P13) L is 5T4- ] o AHs UvNvy H H z- °v°HonnH0 H ° H 9 H 9 H 0 10EL; <yNHLYN^LN^rN^“'N^trN^LN^rN^N^N^lNH214) L is 5T4- J1JACNA0F Nth11 EL;HO-HO JDAR 15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; ° 0 10) L is 5T4- L 8EL;0. 11) L is 5T4-9; SD 12) L is 5T4- H O >Ho V I9EL;V' A VY^N 'NH>o AH0 UJOANH O13) L is 5T4- ovy o <v / wN^vzO « Sr,~u10EL; / ^. NH H O0H14) L is 5T4-FA^UNC IAjh 11 EL;V v o J15) L is 5T4-H°v° DAR12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; o 9 10) L is 5T4- _ ]L- 8EL;°\ 11) L is 5T4-9; ^N' ^N^^Y^N HN^^>NH12) L is 5T4- °H° ^ Y O^NH 1 0 1 Q 1 9 1 9 1, 9 Y9EL;X £ H o H J H £ H13) L is 5T4- X6JG°F N~tk\ P 10EL;<HOVo J 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; / ° O 10) L is 5T4- L8EL;0^0 11) L is 5T4-9; H 0 > H 9'YN<r-W'NN HNAZN, NHy 12) L is 5T4- O A H oQ* NH I O 1 0 1 9 | o 1 9 f0.6lVNzAN^N^N^NzAN^NzAN'^rNzANH29EL;AH0HO HOHO H013) L is 5T4- VFIXNX IWA J 10EL;Hx o DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- S8EL;A 11) L is 5T4-9;Y A Yr HN^-- VV 12) L is 5T4- 9EL;13) L is 5T4- YJOAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;A ° o A 9) L is 5T4-7EL;L ^ 43 S 10) L is 5T4- °8EL;%J H 9 I H 9 \ 11) L is 5T4-9; AAW N HN^ 'NH(o AHo AA J CA ANH | 0H0 | 0 | oH00^6 Y, N. 12) L is 5T4- Y ^ ^ N ' ^, N. Y1N,N-u N—^, N, -u N-^N. Y^M NUH9 / -^.'NH 01010H010 9EL; AAA J 13) L is 5T4-F NA) DARHopb 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;S 9) L is 5T4-7EL; L °>10) L is 5T4- 1 8EL;11) L is 5T4-9; 12) L is 5T4- XXX / k0 \ 9EL;HC<= DAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; AXX / AI12) L is 5T4- 1z yJDAR 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)17) L is 5T4- 14EL;15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;Q o'N"~ NH 6) L is 5T4-5EL;L — S7) L is 5T4-5EL- X>H O IHo S* VH;¥NN HN^NH18) L is 5T4-6EL;0, 0.,-NJ?. N / OH f9) L is 5T4-7EL; nlH H°CJ °? I oAWUYNYWY°= H° O\HO10) L is 5T4- V 7° I 9 I H o 8EL;1HOVo 0 AVNHVHo )2J HO y 11) L is 5T4-9;DAR 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL; / ° 0 -x5) L is 5T4-4EL; L—06) L is 5T4-5EL;LH? H r\n O <:° °^N’ 1 7) L is 5T4-5EL- 'y^rAN\^NHNA- / Z'NH°0HN^°°X H 0O4H O.H HN\ Io, o C^N'VN^OH / / O°HVH; n, NH H on °H? i n 8) L is 5T4-6EL; HTH0 X NH0 / JN^f n’; z / o TCo oM nA. 9) L is 5T4-7EL;0 '■■' T 0 j Lv OHNO< Z aYCd 10) L is 5T4- HO DAR 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- C0o VL;L- 5) L is 5T4-4EL; l0H2,I H n>H0.HO ° °VX'; V 6) L is 5T4-5EL; v - N' 'N ZN HN'Z'NH 0HN T31°H 0AA OAH 0, H HN'AH < 7) L is 5T4-5EL- o, oLAN7>, N^OH / o IA 'NH H°n ° ° I A VH; n rM0A A lZ nh°'?npF Nj \> p ° -NAon8) L is 5T4-6EL;oM HA.'• T 9 i A oHNo< " A o- 6NHA> J 9) L is 5T4-7EL;HO7DAR 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; C'4) L is 5T4-3EL- ^VL;5) L is 5T4-4EL; j = V > 6) L is 5T4-5EL;V 7) L is 5T4-5EL- A YVV ACHNK00VH;H°Y” 8) L is 5T4-6EL; ACHNVt HQ / "°H9) L is 5T4-7EL;j' DAR 10) L is 5T4- 8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL;O 1 o 1 o 1 o 1 o 3) L is 5T4-3EL; -^ N N N N N *_ O N 0 0 0 0 0 4) L is 5T4-3EL- H 9 I H Y _ _ L^N, 0H- - -yO, ZHO Uy-NA.. O / ^. N / Uy [ VL;A O OHO o A 5) L is 5T4-4EL;YY '^H6) L is 5T4-5EL;Yf p 7) L is 5T4-5EL- HOTY DAR VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; A U? t!?H? H o 3) L is 5T4-3EL;rAN^N^N^N^N^N^N^N^N''V0HHn o n, iHn°YNH H°H°H°H°HO _ — —L4) L is 5T4-3EL- V' / NV A 0 H °Yy^ — — — "VL;Z. 0 0H0 o / *< NH 5) L is 5T4-4EL;6) L is 5T4-5EL; I P1 H0*: _ 7) L is 5T4-5EL-v 0DAR VH;8) L is 5T4-6EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL;A U? t!?H? H o3) L is 5T4-3EL;Hn o TT, iHn°YNH H 0 H°H_ oHoHo __ — — —, L.VYW A O H °YA - -yO ZHO I 4) L is 5T4-3EL- 0 0H0 0 Y VL;. NH5) L is 5T4-4EL; 6) L is 5T4-5EL;\^ / °HOT \V x JDAR 7) L is 5T4-5EL- VH;WSGR Docket No. 63125-725.601Conjugates Antibody (L)8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;H Q OH 11) L is 5T4-9;_ O^NH 0 °H 0 i H Y 12) L is 5T4- \, N, AMYNA, r. 0.Y [ N Y Y Y oHrv^L9EL;1 o AH0Y 0<y-0Ho o > 13) L is 5T4- | YY'NH10EL;14) L is 5T4- F^NY YYzo 11 EL;HOVo J 15) L is 5T4- < DAR 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9;0NH I o 1 O I o ' 0 1 0H 9 i H Y _.u. 12) L is 5T4- Y'AW 0 H °Yv____— - - - Y O^OH0 o Y 9EL;13) L is 5T4- 10EL;Y. PIHOVo \ 14) L is 5T4- ^ DAR 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;O | O | O H O | O 10) L is 5T4- ^ N N N N NoNH 0H0 0 0H0 8EL;H 9 1 H Y „ 1^N, JNVYA Oh- - - 11) L is 5T4-9;) 0, 6HO o V 12) L is 5T4- ) YY'NHI9EL;3,0 13) L is 5T4-HO\ o 10EL;V JDAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;0 | 0 | 0 H 0 | 0^ NNA M N-~NA NN-Y N NNH2Z10) L is 5T4-oNH 0H0 0 0H0H 9 i H Y _. 8EL; V / NW O H °YA ^ - - - '0 / kHO Uy-,NJY-O^--O'^NY^'^Y 11) L is 5T4-9;) OyO H o o UY < Y 'NH\ 12) L is 5T4- 'AOUA 9EL;13) L is 5T4-HOY OV JDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; C 9 O H O 0H9) L is 5T4-7EL;0 ^N^N^N^N^N^N^N^rN^OHNH 0 0 0 0 10) L is 5T4- V JJ f0N^ JUNYJ^CI ° _ _ _ L 8EL;O H - - - J o H o tAy- 'N^o- O^Nv 11) L is 5T4-9;“N 0, 6HO o (. NH 12) L is 5T4- 9EL;Y ° 13) L is 5T4- IH° ’ o Jv yDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9 I 9 H O | OHO ^Ip N Y N Y N Y N Y NH2NH 0 0 0 0 9) L is 5T4-7EL;H O 1 H _ _ L 10) L is 5T4- Y' / NN0 H\ O / H0 rz / N-, O. / oz,. N / , N Y IA 0 6H0 0 A 8EL;z-\. NH 11) L is 5T4-9; YI YNY^ 12) L is 5T4- A, p\HOVo J 9EL;VAAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;Z HO I O 7) L is 5T4-5EL-. I H sn ' O VH;0 = H 0 °. NH8) L is 5T4-6EL;H ° ‘O^L^YNYJV9) L is 5T4-7EL; J 'NA^OHNH O1 H\n 0^ / KH ° I H _ > 10) L is 5T4- ) Y'MNrS oH( 8EL;0,6H0 011) L is 5T4-9;'NH12) L is 5T4- AL / ° 9EL;) HOTA. )DAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;X'HO\ 6) L is 5T4-5EL;( d N_AN.\<NH2 )j j » H i 7) L is 5T4-5EL- n * ^0oHo °Y-NHVH;HSt T°[ / >fNY#'N'V-OH 8) L is 5T4-6EL;NH O1 H9) L is 5T4-7EL; W / NVA O H LA <10) L is 5T4- OyO H o 0LO 'NH8EL;11) L is 5T4-9;\_ PH0*t~C J 12) L is 5T4-s-^DAR 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; C 3) L is 5T4-3EL;Ho°A NA ru> NH OHN „ 4) L is 5T4-3EL- HN— ( / XL HQXVN=ZHNAO A yA Y ° VL;. ^0 NHO 5) L is 5T4-4EL;O^NH^S=O6) L is 5T4-5EL; °VN 1 C>^°oho 'wNA HN. J 7) L is 5T4-5EL- >NH 0HN^O VH;Y 7 A~£>OA" V\ VNH. VA A 8) L is 5T4-6EL;HN' ( )-NH / 9) L is 5T4-7EL;\ oNHn0=O\H0^ / \ 10) L is 5T4- H 9 1 H 7V'AVYS OHL8EL;o<^dHo o 11) L is 5T4-9;O 'NH12) L is 5T4- 9EL;P13) L is 5T4- IHOVo JDAR 10EL;14) L is 5T4- 11 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- <OHVL;HO5) L is 5T4-4EL;H^O NH°HMOUAc\HNHOACHNHN^° 6) L is 5T4-5EL;7) L is 5T4-5EL- J YAVA O „N. 0 AHO Uy-fjA. O^Q^Ny^NY^ ( VH;O<yOH0 OO'NH8) L is 5T4-6EL;9) L is 5T4-7EL; XXXN~f5_ P 1 10) L is 5T4- LH°’<°yDAR 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL;° *U 2) L is 5T4-2EL;1 L3) L is 5T4-3EL;0.4) L is 5T4-3EL- %ho ih9 V VL;V'AV'IA HN-<- Y'NHU " j WO1NH O5) L is 5T4-4EL;°Y° 'JN '.nsnH6) L is 5T4-5EL;1, NXH00H>■7) L is 5T4-5EL- O^NHVH;8) L is 5T4-6EL;0* 31 J.0"^N"\ 9) L is 5T4-7EL;10) L is 5T4-N^vU / < HO JDAR8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL;0? 2) L is 5T4-2EL; L — _ Z'N'^ANH^0 S 3) L is 5T4-3EL;o 4) L is 5T4-3EL- H O I H 0 A0VL;V'ANVYA HN'-^VHo. " 4 VU0iNH 05) L is 5T4-4EL;6) L is 5T4-5EL; AAHo'oHv.7) L is 5T4-5EL- CANH (\ A^o VH;8) L is 5T4-6EL; °1C)A ] ^\ 9) L is 5T4-7EL;10) L is 5T4- A o 8EL;\H0 / vDAR 11) L is 5T4-9;12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL;0 0LS 2) L is 5T4-2EL;Ch% 3) L is 5T4-3EL;Ho IH0 ’5°, N,.; LN / HN^^ 'NH4) L is 5T4-3EL- oHo LAA,-AVL;, °Y° N^N^NHAA 'NX H oH0HoHo A 5) L is 5T4-4EL; O NH6) L is 5T4-5EL; A 7) L is 5T4-5EL- O N,VH;A^ / N^A?HHO " - / 8) L is 5T4-6EL;DAR9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;0? 9) L is 5T4-7EL; L—S 10) L is 5T4- 0u 8EL;H 0.H0HN^-NH11) L is 5T4-9; o AHo UO A12) L is 5T4- J H oH0HOHoCANH 1 9EL;13) L is 5T4-01]CJ N" A 10EL;14) L is 5T4- ■■ ■HHJ ^ J 11 EL;DAR 15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;0? 9) L is 5T4-7EL; LS 10) L is 5T4- CL% 8EL;H 9 | H 0 A°YN‘ / N\N^ HN^ 'o A H o LU ANH11) L is 5T4-9;0 NH 0 ■ u°Y° U-A " TNA0H12) L is 5T4- A AHo Lo AA / N H O! \ AOAH UrNAN 9EL;N('A^0. 0z H0QUNH13) L is 5T4- A AA" A 10EL; Ct Y HOA At??14) L is 5T4- A N^UU )HHO " A_11 EL; DAR15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.Table A-S: Specific Conjugates of the DisclosureConjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- ^ VH;L°>8) L is 5T4-6EL; L9) L is 5T4-7EL; J0VY\0"' f 10) L is 5T4- 1 °Y°\ 1 V 8EL;VVV^ z°11) L is 5T4-9; <~\ z012) L is 5T4- j 9EL;y DAR13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)16) L is 5T4- 13 EL;\17) L is 5T4- ZZ^ / > O= 14EL;O f> y°- 18) L is 5T4- > \O O z 15EL;d t°p / -ox ° vZ Zp— y 19) L is 5T4-16; y b z ioZI 20) L is 5T4-17;So=Z I21) L is 5T4-18; 4 □ ZIV 'o 22) L is 5T4-19;IZ4 o 23) L is 5T4-20; zzVo zz or4 □ zz 24) L is 5T4-21.Vo zz 1) L is 5T4-1EL;4 □ zz 2) L is 5T4-2EL;VoS O k 7 _ _, 3) L is 5T4-3EL; > V7) 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;L7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;0 0 " X 5) L is 5T4-4EL; L- - AN^^NHT3 1CL 6) L is 5T4-5EL;% 7) L is 5T4-5EL- 11 0 | H Q ^7^^N-A V^I HN^ 'NHI VH;0 H° cr 'NH H o H 9 H 9 H 9 H 9 (OyO V^N^N^N^rN^NH2yy. NH 0H0HOH0H0 8) L is 5T4-6EL;9) L is 5T4-7EL; nWF^'^Nv Ai AL,010) L is 5T4- HO*T"< Jx° DAR 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;0 0 4) L is 5T4-3EL- L- - VL;° 5) L is 5T4-4EL;%H O i H 9 6) L is 5T4-5EL; -. N. “ NJ^N ZHN^> 'NHVo / CHookN^0o i o i o o (o, oLVN^N^N^N^N^N^TN^AN^¥N^AOH7) L is 5T4-5EL- o O101O10VH;XXTN^08) L is 5T4-6EL; k V PHO^ 7 9) L is 5T4-7EL;DAR 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; o o AL _ Z N ' / NH 4) L is 5T4-3EL- °0VL;%H 0 i H 9 5) L is 5T4-4EL;A n HN^-NHyo / CHo O^N'' 1 0 1 0 1 0 1 0 | o ( 6) L is 5T4-5EL;0,0 yN^N^N^N^N^N^N^N'''YN''->NH20 01O1010 7) L is 5T4-5EL- 'XXYW VH;F Ni h< / ° } 8) L is 5T4-6EL;"°<° DAR9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL;r 00 2) L is 5T4-2EL; 1 1—^0 S 3) L is 5T4-3EL;0.^0 4) L is 5T4-3EL- H 0 1 H 9 ° \'YN-ZN\NY^ HN^>NH\ VL;0 H 0O NH I 0 1 0 1 0 1 0 1 00, 0 CN^N^N^N^N^N^¥N^AN^YN^ANH25) L is 5T4-4EL;, NH 0 H 0H0H0H06) L is 5T4-5EL;TO WV k. / ° y 7) L is 5T4-5EL- H0<~<0DAR VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; L— A S 7 2) L is 5T4-2EL;3) L is 5T4-3EL; H HrrNfANriHN4) L is 5T4-3EL- J^ANHH) °Y° V^NA "-A^Y " AY-AH A VL;5) L is 5T4-4EL; 'XXX / 1\ ° 6) L is 5T4-5EL;H°A°7) L is 5T4-5EL- DAR VH;8) L is 5T4-6EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4-13 EL;17) L is 5T4- 14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;WSGR Docket No. 63125-725.601Conjugates Antibody (L)8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 0 0 AL- 9) L is 5T4-7EL;0. 10) L is 5T4- LH? H r\n O ^°0< KTN¥^N...|_i 0 i 9 l10 A^A- 8EL;^N' ZN^Ny^A oHA 11) L is 5T4-9; o. o / -y° (n, NH H°cNo i n CM 12) L is 5T4- A "nN‘ H A A MoNH0A 9EL;A p "’A O. A OHNOH° VoN■ ' K0NH N" 13) L is 5T4- HC>10EL;DAR14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;Z°08) L is 5T4-6EL;L — - CX 9) L is 5T4-7EL;L H2N rA 10) L is 5T4- u n 0 | H 0 O ^f ° 1 oyfN. JN\NYA 8EL;°H° O^NH O. H \ IJ > 11) L is 5T4-9; niNH H°n °? i o i 12) L is 5T4- I T ri\ p i 9 i Cy oHNo 9EL;ho<o o " n\ M H oNH) LA 13) L is 5T4- HO10EL;DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL;N^N'" YN^'N'^YN^NH9) L is 5T4-7EL; y10) L is 5T4- J \ L 8EL;v W n 11) L is 5T4-9;12) L is 5T4- XUCM0^ 9EL;V J DAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;DAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;L06) L is 5T4-5EL;7) L is 5T4-5EL-0s0.VH;%1 0 8) L is 5T4-6EL;\0V 9) L is 5T4-7EL;1 H0I H 9 ';° / VR, HN^'NHf 10) L is 5T4- O / L.H0 O N 1 0 1 0 1 0 1 0 1 00, 0 krN^N^N^N^N^N--YN^AN^YN^A0H^.. NH 0 0101010 8EL;11) L is 5T4-9;F U l M \0—\ Y_ PH0*W 7 12) L is 5T4- DAR 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;° 0 6) L is 5T4-5EL;7) L is 5T4-5EL- S VH;L^X° 0 / H 0! H 9 ' ° 8) L is 5T4-6EL; AYN' HN^^'NHI0-"-" CH° Ck'y-J O^N'' i o i o i 9 i 9 9 {0^,0 ^N^N^N^N'^YN'^XN'krN^AN'krN'-A0H 9) L is 5T4-7EL;^.. NH 0 O101O1010) L is 5T4- 'XXSTM08EL;\ V / °H0Vo J 11) L is 5T4-9;DAR 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;< V >v HN^-™ 8) L is 5T4-6EL;\'N^N^N'-^~N'~YN'-^U'N'~YN'-^'N'^B'N'^'OH 9) L is 5T4-7EL;O W 10) L is 5T4- HOTA 8EL;V J DAR11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;_.. LH° i H 9 p 6) L is 5T4-5EL; / Y’AV'fN 9< s AH0 H I 7) L is 5T4-5EL- I °Y°HO^bG I 0 I 0 1 0 I 0 I 0 (YY'NHSfN^LN^rN^N^rN^N^fN^“'Nx>rN^1'oH VH;n 010101010YYXV<F"xy'NY A 8) L is 5T4-6EL;,oHO-H I 9) L is 5T4-7EL;DAR 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- L VL;1 5) L is 5T4-4EL; H o i n 9 pN' YN'TCN9 - oy lHo.N.... NH H I > 6) L is 5T4-5EL;° °HoXxI 0 I 0 I 0 I 0 I 0 7) L is 5T4-5EL- X ^X. NH V^N^N^N^N^N^N^N^N^NH20 ° ' ° 0 ' 0 0J I XM VH;1 V 0HO-H J 8) L is 5T4-6EL;DAR 9) L is 5T4-7EL;10) L is 5T4- 8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;H 0 i H 9 P> TN' / 'NAYN'7PN 0J O AHo H 1 5) L is 5T4-4EL;) ° °HCT NHO-NH ^NH0 H 9 H 9 H P H 0 >^N^N^N^N^N^¥N^AN^¥N^A0H6) L is 5T4-5EL;,, n 0HO H o H o H oX 7) L is 5T4-5EL-FXNXM L A VH;L \ ° J8) L is 5T4-6EL; DAR 9) L is 5T4-7EL;10) L is 5T4- 8EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- J H0I H 9 P VL;P AHO NH H < 5) L is 5T4-4EL; / XJHHO^~N CHHN^OtN^IfHNy9iN^ HNy9tN^HNy 9tN^fHNy 9tNH26) L is 5T4-5EL;. 1 1 n oHoH0H0H0TYTH7) L is 5T4-5EL- i z°^VoJVH;DAR 8) L is 5T4-6EL;9) L is 5T4-7EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- ° o 8EL;L _ / 'N'^XANH 11) L is 5T4-9;o. 12) L is 5T4- % 9EL;H 0 iH0Lxf° I13) L is 5T4- V' M YN HN^ >NH>o AH0o4 o 10EL;0^,0YvN. S nu / ^. NH H O'0H14) L is 5T4- 11 EL; u XHt 15) L is 5T4- V \ o JHO12EL;Vo DAR16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- <00_ ] 8EL;L- CL 11) L is 5T4-9;%H O i H 9 ^4* 12) L is 5T4- 'YN'AN\'N> PN HNJ^^|'NHIO / CH 0O^NH 1 0 1 0 1 o 1 0 | o S- 9EL;°Y in nN'A> H| 13) L is 5T4- 10EL;FXTnXYYYi k0\ PHO14) L is 5T4- < tt JDAR 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- z ° oL 8EL;0° 11) L is 5T4-9;X)H 0 i H 9 12) L is 5T4-N' AN\'N> PN HN >'NHy°H° C / NH 1 O 1 0 1 0 1 0 1 0 < 9EL;0, 0 ^N^N^N^N^N'^'N'^YN'-ANyfN'-^'NH2^. NH 0HOHOHOH0 13) L is 5T4- IXxW 10EL; VF NJHx o DAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;— \11) L is 5T4-9; AVTS 12) L is 5T4- VyV S ^ ^ ^ ^ ^ ^ 9EL;13) L is 5T4- 10EL;yJOAR14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; r ° o10) L is 5T4- L— S0. 8EL;% 11) L is 5T4-9;J H 9 | H 9 V V.N- / NNNNHN^^ ~NH\0 / L H 0 k. Jk J -X 12) L is 5T4- O^NH | 0H0 I 0 I 0H0CK o L N A ^ N A / \ N A ^ N A X^ N A0 0 0H0 0 9EL;13) L is 5T4- yxx>kt JFDAR 10EL; Ho^no14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;S 10) L is 5T4- L °>8EL;1 11) L is 5T4-9;f12) L is 5T4- 9EL;XXX / k0 \ 13) L is 5T4-H0^ o DAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL; ¥Z 'Z T IV V ^N^NZ -N- YN^N- ZN^NH2 11) L is 5T4-9;12) L is 5T4- F' -' N' ' / / ~~\9EL;IHO*H) )z yDAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- ° O_ _ / N ^H VH;S0. 8) L is 5T4-6EL;%9) L is 5T4-7EL;H 0 i H 9vW n0 H0 O NH 0.H. 10) L is 5T4- 0. 0 kAN\, N^OH <8EL;rrH°o H? i oXTVM00 - H A OOXXNH 11) L is 5T4-9;V 7° "" T 0 I H 0HO\ O oxYr*™ 12) L is 5T4- HO J9EL;DAR13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; r ° o 6) L is 5T4-5EL;'N'" NH 7) L is 5T4-5EL- L - " SCX VH;U H O i H 908) L is 5T4-6EL; AYNW N HN^'NH" A O / AH0 >f.-" CANFI o.hV 9) L is 5T4-7EL;o. o kANA^N^OH (10) L is 5T4- HIH HA H? I OFUNAk0; H° O\HO8EL;Y Z° " ’ 9 1 H o 11) L is 5T4-9; 1HOVo 0 HV'AHJ°HO^ y 12) L is 5T4- DAR 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; / 0 0-xN"" A 6) L is 5T4-5EL; L SOx 7) L is 5T4-5EL- toHp>n o:°Ny- NH 0 i H 9 l * 0 VH;>fN' ZN\N-pN HN^'NHHN^-0°H 0kA / OAH o.H HN-S < 8) L is 5T4-6EL;o o N rN X 0H, / o (n, NH H on H? i nZA 9) L is 5T4-7EL; YTTN? ANYN\NY YNH°A A10) L is 5T4- \ p0■O OKHA f A 9 ^ j AN? oHN.oH°Vo 0 YNHN "Ix H0 ) Lv 8EL;HO / DAR 11) L is 5T4-9;12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;0° 5) L is 5T4-4EL; L- _ / ^ NH0°> 6) L is 5T4-5EL;L H2N H O7) L is n O ° O^NYLNH 0 i H 9 116, / -< 5T4-5EL- V' ZN\'NY^N HN^-01 VH; °H 0AyJ O NH 0.HHN'AU A0 0NAN<°H; / oOH8) L is 5T4-6EL; rrNH H°n H? i n CMJ AFN4-° A l 'WJ FWIL 0 - H o0^NHXN;. 9) L is 5T4-7EL;-'V 0° OHNO10) L is 5T4- < " A o »VT6 J HO78EL; DAR11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- C'VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- J f Y >VH;_ HOLA*ACH 7NX\° 8) L is 5T4-6EL; LALH X” 9) L is 5T4-7EL;ACHNX- HOVOH 10) L is 5T4- A°' -> DAR 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;O 1 o 1 o 1 o 1 o 4) L is 5T4-3EL- -^ N N N N N *_ O N 0 0 0 0 0 VL;H 9 I H Y _ _ L^N, 0H- - - 5) L is 5T4-4EL;A O OHO o A 6) L is 5T4-5EL;YY '^H7) L is 5T4-5EL- Yf p VH;HOTY DAR 8) L is 5T4-6EL;9) L is 5T4-7EL; 10) L is 5T4- 8EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; A U? t!?H? H orAN^N^N^N^N^N^N^N^N''V0H4) L is 5T4-3EL-Hn o n, iHn°YNH H°H°H°H°HO _ — —LV' / NV A 0 H °Ay^ — — — " VL;A o oHo o A 5) L is 5T4-4EL;< NH6) L is 5T4-5EL; A o 7) L is 5T4-5EL- 1 H07 -v 0DAR VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 9 t!?H? H oH0 3) L is 5T4-3EL; H 0, H °YNH° °H°H°H° L 4) L is 5T4-3EL-yYN- -A | N N A Y<N' YYXY1n oH°v T-zHY\ — — — — —O O i VL;Y o,oHo o Yzx, NH 5) L is 5T4-4EL;6) L is 5T4-5EL; Y pHOTY 7) L is 5T4-5EL-x JDAR VH;8) L is 5T4-6EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;H Q OH 11) L is 5T4-9;_ O^NH 0 °H 0 i H Y 12) L is 5T4- \, N, AMYNA, r. 0.Y [ N Y Y Y oHrv^L9EL;1 o AH0Y 0<y-0Ho o > 13) L is 5T4- | YY'NH10EL;14) L is 5T4- F^NY YYzo 11 EL;HOVo J 15) L is 5T4- < DAR 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;J ^OH 11) L is 5T4-9;0NH I o 1 O I o ' 0 I oVNH9, A\ I -HY o iNv4. n Ck ______ - - - 12) L is 5T4- T 1 N n T n 9 H TA _ _L1 oHo 1T QyOH0 0 T 9EL;O 'NH13) L is 5T4- XXXJN-? 10EL;\_ p1 HO-M 1 14) L is 5T4- - DAR 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL;O | O | O H O | O 10) L is 5T4-oNH 0H0 0 0H0 8EL;H 9 1 H Y „ 1^N, JNVYA Oh- - - 11) L is 5T4-9;) 0, 0HO o V 12) L is 5T4- ) YY'NHI9EL;3,0 13) L is 5T4-HO\ o 10EL;V JDAR 14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 0 | 0 | 0 H 0 | 0^ N N N N NZ10) L is 5T4-oNH 0H0 0 0H0H 9 i H Y _. 8EL;V'AVA O H °YA ^ - - - 'o / kHO 11) L is 5T4-9; ) O O H o o IY, >nhY 12) L is 5T4- 9EL;YY° 13) L is 5T4-H°YoV JDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; C 9 O H O 0H9) L is 5T4-7EL;0 ^N^N^N^N^N^N^N^rN^OHNH 0 0 0 0 10) L is 5T4- Y JJ' / 0'N' JYUNJC ° _ _ _ L 8EL;'A O H - - - J o H o tAy-N- o o-NY^N. I11) L is 5T4-9;“N 0, 0HO O, NH 12) L is 5T4- 9EL;Y ° 13) L is 5T4- IH° ’ o Jv yDAR 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9 I 9 H O | OHO ^Ip N Y N Y N Y N Y NH2NH 0 0 0 0 9) L is 5T4-7EL;H O 1 H _ _ L 10) L is 5T4- Y' / NN0 H\ OH0 / N^, O. / oz „N / , N Y IA 0 0H0 0 A 8EL; / " AH 11) L is 5T4-9; 'XAAQ^L 12) L is 5T4- A, p\HOVo J 9EL;vDAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;Z HO I O 7) L is 5T4-5EL-. I H sn ' O VH;0 = H 0 °. NH8) L is 5T4-6EL;H ° ‘O^L^YNY 9) L is 5T4-7EL; JJV'NA^OHNH O1 Hi 10) L is 5T4- vi uao H0 AHo C 8EL;0,0H0 011) L is 5T4-9;'NH12) L is 5T4- AL / ° 9EL;) HOTA. )DAR 13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; tr20) L is 5T4-17; _ _ A? 21) L is 5T4-18;CMX lz 22) L is 5T4-19;>o / =zx o 23) L is 5T4-20;$- / / XZo=X)O 1= or / 1 y / HO\ 1T24) L is 5T4-21.0 O\ °H1) L is 5T4-1EL;$ >o—=o=xz xz 2) L is 5T4-2EL;5?p O 9 ZX C. ° 3) L is 5T4-3EL;% $A °JrO J o*oo14) L is 5T4-3EL- VL;y ynta 5) L is 5T4-4EL; ^ y{°== ( xz> — 'z x< M °6) L is 5T4-5EL; °<,= zx7) L is 5T4-5EL- > 2Z '_ _ < J VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; C 3) L is 5T4-3EL;Ho°A NA ru> NH OHN „ 4) L is 5T4-3EL- HN— ( / XL HQXVN=ZHNAO A yA Y ° VL;. ^0 NHO 5) L is 5T4-4EL;O^NH^S=O6) L is 5T4-5EL; °VN 1 C>^°oho 'wNA HN. J 7) L is 5T4-5EL- >NH 0HN^O VH;Y 7 A~£>OA" V\ VNH. VA A 8) L is 5T4-6EL;HN' ( )-NH / 9) L is 5T4-7EL;\ oNHn0=O\H0^ / \ 10) L is 5T4- H 9 1 H 7V'AVYS OHL8EL;0<^0Ho o 11) L is 5T4-9;O 'NH12) L is 5T4- p 9EL;13) L is 5T4- IHOVo JDAR 10EL;14) L is 5T4- 11 EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- < 13 EL;17) L is 5T4- 14EL;\ o <18) L is 5T4- 15EL;1 c- 19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; <°r X > o\ o °T22) L is 5T4-19;23) L is 5T4-20; X 4K ri " orok124) L is 5T4-21. y iz e ' — CJH °^ / < O== 1) L is 5T4-1EL; ZIO< / = 2) L is 5T4-2EL; IZ '_ _ J?°= 3) L is 5T4-3EL;4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL;° *U 2) L is 5T4-2EL;1 L3) L is 5T4-3EL;0.4) L is 5T4-3EL- %ho ih9 V VL;V'AV'IA HN-<- Y'NHU " jOJ.NH O5) L is 5T4-4EL;°Y° 'JN '.nsnH6) L is 5T4-5EL;1, NXH00H>■7) L is 5T4-5EL- O^NHVH;8) L is 5T4-6EL;0* 31 J.0"^N"\ 9) L is 5T4-7EL;10) L is 5T4-N^vU / < HO JDAR8EL;11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.WSGR Docket No. 63125-725.601Conjugates Antibody (L)1) L is 5T4-1EL;0? 2) L is 5T4-2EL; L — _ Z'N'^ANHA S 3) L is 5T4-3EL;o 4) L is 5T4-3EL- H O I H 0 A0VL;V' AVri HN'-^VHU H S L.R 0JN„05) L is 5T4-4EL;10' °1 N' °SOH \ 6) L is 5T4-5EL; AAHo'oHv.7) L is 5T4-5EL- CANH (\rAf>° VH;8) L is 5T4-6EL;1cAlW 9) L is 5T4-7EL;10) L is 5T4- A o 8EL;\H0 / vDAR 11) L is 5T4-9;12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; orWSGR Docket No. 63125-725.601Conjugates Antibody (L)24) L is 5T4-21.1) L is 5T4-1EL;0 0LS 2) L is 5T4-2EL;Ch% 3) L is 5T4-3EL;Ho IH0 ’5°, N,.; LN / HN^^ 'NH4) L is 5T4-3EL- oHo LAA,-AnX ° NH 1 O 1 O 1 0 1 0 1 0 VL;, °Y° N^N^NHAA 'NX H oH0HoHo A 5) L is 5T4-4EL; O NH6) L is 5T4-5EL; A 7) L is 5T4-5EL- O N,VH;A^ / N^A?HHO " - / 8) L is 5T4-6EL;DAR9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19;WSGR Docket No. 63125-725.601Conjugates Antibody (L)23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4- 10EL;14) L is 5T4- 11 EL;DAR 15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18;WSGR Docket No. 63125-725.601Conjugates Antibody (L)22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4- 9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4- 12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16; 20) L is 5T4-17;WSGR Docket No. 63125-725.601Conjugates Antibody (L)21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL-VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4- 8EL;11) L is 5T4-9; 12) L is 5T4-9EL;13) L is 5T4-10EL;14) L is 5T4- 11 EL;15) L is 5T4-12EL;16) L is 5T4- 13 EL;17) L is 5T4-14EL;18) L is 5T4-15EL;19) L is 5T4-16;WSGR Docket No. 63125-725.601Conjugates Antibody (L)20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.
[0169] Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 1 to about 8. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 2 to about 8. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 2. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 3. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 4. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 5. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 6. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 7. Conjugates of Table A, Table A-S, and Table A-R, each independently have a DAR of about 8.Table B: Specific Conjugates of the DisclosureConjugates Antibody (L)1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL 9) L is 5T4-7EL 10) L is 5T4-8EL 11)L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12)L is 5T4- 9EL;13)L is 5T4- 10EL;14)L is 5T4- 11 EL;15)L is 5T4- 12EL;16)L is 5T4- 13EL;17)L is 5T4- 14EL;18)L is 5T4- 15EL;19)L is 5T4-16; 20)L is 5T4-17; 21)L is 5T4-18; 22)L is 5T4-19; 23)L is 5T4-20;or 24)L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; c °? 3) L is 5T4-3EL;- 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;J iX Ov S: % IV 6) L is 5T4-5EL;H< QSA0HYW ACHNX 7) L is 5T4-5EL- W E Y VH;p HO^AOHXA° 8) L is 5T4-6EL;' y DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9;WSGR Docket No. 63125-725.601Conjugates Antibody (L)12) L is 5T4-9EL; 13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; o 0 4) L is 5T4-3EL- L— - ^N^ANHCk VL;% 5) L is 5T4-4EL; 0 0 VHO'UY°'r-°Y^ HNJ^^r'NHI 6) L is 5T4-5EL; HO' Y '" OH ^ V °XHH 9 H 0 H o H 9 tj? f. NH oHOH0Ho H o 7) L is 5T4-5EL- Trxw VH;F NthV.HO-HOJ 8) L is 5T4-6EL;DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4-, ' _ _ Q A 12EL;CM X16) L is 5T4- zz13EL;zx17) L is 5T4- xzr° 14EL;zx$ °= 18) L is 5T4- xzf°zx 15EL;xz 19) L is 5T4-16; zx 20) L is 5T4-17; xz 21) L is 5T4-18; q i x >o=22) L is 5T4-19; r rV ■G°°VW< o=( z o J o= 23) L is 5T4-20;1°1or ZA_ \ / E00=\7= oo 24) L is 5T4-21.O oo u- '( o b=o * 1) L is 5T4-1EL;_ X,2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- L VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;O oL- - - 4) L is 5T4-3EL- o.VL;X)0 o V 5) L is 5T4-4EL;Ho\V^ HN^ 'NHLH0'" I O^t< 1 O 1 O 1 o | O J.? fOH O^O ^N^**'N^I1'N^U'N^|fN^U'N^n'N^'N^rN^OH 6) L is 5T4-5EL;^X, NH O10101O1O 7) L is 5T4-5EL- n wVH;< AL / °HOT? J 8) L is 5T4-6EL;DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;r0 0_ (AN'' — “'NH 4) L is 5T4-3EL- L- CL VL;%O 0 S*05) L is 5T4-4EL; HO^°Y°'Y^] HNA^>'NHyHO1' Y "0H CANXI 0 1 0 1 0 1 0 I 0 <0H6) L is 5T4-5EL;OyO k^N^N^NAkN^fN^>tNx\tI, N^ltN^I, Nv>lNH2010101010 7) L is 5T4-5EL- IYYW VH;F NU~Ai A P J 8) L is 5T4-6EL; HO*M. _DAR9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- - -0?L NH VL;05) L is 5T4-4EL; O O VHOJUo^O^ HN^^r'NH6) L is 5T4-5EL; HO- Y ’" OH T °"NHi 9 i 919 J,? J,?OHOH0,0 ^N^NYrN^N'YN^N'~YN^NYrN'-A°H7) L is 5T4-5EL- f^H o H 0 H o H o HOVH;8) L is 5T4-6EL; HOV DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;0 0L 4) L is 5T4-3EL-0VL;u0 o -O 0 U V 1 \ 5) L is 5T4-4EL;HOTI \> HN^ 'NH>H0 0HOANH I 0 1 0 1 0 1 0 1 9 6) L is 5T4-5EL;o o CN^N^N^N^N^N^N'-^'N'~YN'-ANH2.^H 0HOH0HOH0 7) L is 5T4-5EL- XCCM0VH;f^nvKV / ° yHO-W 8) L is 5T4-6EL;0DAR9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; L — — A S 7 4) L is 5T4-3EL- VL;HOVY°> A 5) L is 5T4-4EL; <H0" ™0H°AH6) L is 5T4-5EL;7) L is 5T4-5EL- VH;H0 / l8) L is 5T4-6EL;DAR9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; ° o- 4) L is 5T4-3EL- ^0 S0 VL;ko00 5) L is 5T4-4EL;Ho^°T°>n HNA^.- 9 9 9 9 6) L is 5T4-5EL;> KTN1H O1111O11H O1111O11H O117) L is 5T4-5EL- ^XJACNALhoV / ° VH;< / \> JDAR 8) L is 5T4-6EL;9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;tr 15) L is 5T4-, <_ _ Q A 12EL;o / = 1 ) O 16) L is 5T4- xz o13EL;zx< o= 17) L is 5T4- y)z-A ''14EL;C: °18) L is 5T4- 15EL;19) L is 5T4-16; ^ro'-" A20) L is 5T4-17; zx21) L is 5T4-18; 22) L is 5T4-19;r4 i oO. / v ° r rV o°- ^°°z J o< o= 23) L is 5T4-20; Am 1°1or { P 1 \= O ro* / °\ / I x U. ' — 24) L is 5T4-21. / V\ ° °( I o b= 1) L is 5T4-1EL; _ _ J y x o12) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- c X° Xx 10EL;) QO=□ 14) L is 5T4- X H 9A= 11EL;15) L is 5T4- f >?0 o12EL;X0v 16) L is 5T4- iz 13EL;^0 ^Vzzz, 17) L is 5T4- ( o=°ZI0, 14EL;V '1oxz18) L is 5T4-?~ o=O V 15EL;H c 19) L is 5T4-16;>0xz20) L is 5T4-17; ^'O=XZI O>o= 21) L is 5T4-18; z 1 r J \ X \ y M 22) L is 5T4-19; O - - Y23) L is 5T4-20; 7)or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;L— 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- I \ / 1q z> qo= 10EL;X o □ \ / Z _ 14) L is 5T4- ( 4 ) °=D / x y f°c / = 11EL; f ° xo15) L is 5T4- d t '°pz° 12EL;X ° v16) L is 5T4- zz13EL;Qz x\ Yp o 17) L is 5T4- o. 14EL;IZX O > VO—p X OZI O 18) L is 5T4- 15EL;p°OY>y yo 19) L is 5T4-16;h X °M ° °<° i o 20) L is 5T4-17;21) L is 5T4-18; O< v k )\v y o _ _ _o V 22) L is 5T4-19;23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; L- 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL;0JL 3) L is 5T4-3EL;L—CL 4) L is 5T4-3EL- U H2NHr\VL;o o vHO^r°y°'Y^ HNJ1^>'NH° HN- / * 5) L is 5T4-4EL;HO- Y " OH CT>|H o,H HN'S IOH °Y° CANJyNY~OH _> OOH / > 6) L is 5T4-5EL;n-'NH HVN H o i n CM [ 7) L is 5T4-5EL- F n^NSVvL 30N^ - HT 0 ^1NH oJlfT " VVjb --V 0° X?0HN^0VH;HOVO OA6ONH / C 8) L is 5T4-6EL;HO9) L is 5T4-7EL; DAR 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;J \ 6) L is 5T4-5EL;^HNA^. NH7) L is 5T4-5EL- VH;HYW8) L is 5T4-6EL;V J DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL;N=N «=\LVy o 3) L is 5T4-3EL;0 4) L is 5T4-3EL- (L% VL;J % 5) L is 5T4-4EL; y % >- \ °0yo < 6) L is 5T4-5EL;HO'“v°y°\^ HN^'NHHO- Y'OH o^tr. 0 1 0 1 0 1 0 1 0 7) L is 5T4-5EL- °HO^oLYN'^'N">rN'^N^YN^'N^YN'^l'N'VN'^'OH010101010 VH;U YW 8) L is 5T4-6EL;F Nth,oHOVo J 9) L is 5T4-7EL;DAR 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL;L03) L is 5T4-3EL;4) L is 5T4-3EL-0SCX VL;^01 0 5) L is 5T4-4EL;-<^ x> \ 6) L is 5T4-5EL;1 0 o V >HO ^ O HN^'NH7) L is 5T4-5EL- H(TY'nH O^hT 1 0 I 0 1 0 1 0 1 0OH OVO k-N^N^N^N^N^N^N^AN^YN^A0H / X. NH 0 0101010 VH; 1J XM° 8) L is 5T4-6EL;\ L / °HO< y 9) L is 5T4-7EL;\ oDAR 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- L — 0 o~ ' — — Z N" \Hs VL;5) L is 5T4-4EL;) 0 0 V36) L is 5T4-5EL; <H0i° r Vi HN^> 'NHI HO'" 'OH o^N'' 1 0 1 0 1 0 1 0 O I (0H7) L is 5T4-5EL- 0 0 \fN^N^N^N^N^N^N^N^N'-AoH / x. NH 0 0101010 VH; V rN^° 8) L is 5T4-6EL; \ L / °H°V J 9) L is 5T4-7EL;DAR 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL;5 V 7) L is 5T4-5EL- 1 Y VHN^INH1VH;1TXM° 8) L is 5T4-6EL;9) L is 5T4-7EL;V J DAR10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;j?no 9 o 5) L is 5T4-4EL; sH°' VHYr tex > 6) L is 5T4-5EL;°YUO^N I 0 1 0 I 0 I 0 I 0 (^.. NH YN^N^N^N^N^N^N'At'N''YN'^'OH 7) L is 5T4-5EL- 0T T T iw0 1 0 1 0 1 0 1 0V )~\ VH;YL / °HOVo J 8) L is 5T4-6EL;DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL-VL;5) L is 5T4-4EL;A. n 0 9 P) HoY Y* 0 V'0^'°' / 'N;'^'N-V^^ I 6) L is 5T4-5EL; ) HC / Y OH'OH UnC I^NH^'-YINHxH° rOyU O^N I 0, 0 I 0 I 0 | 0 I7) L is 5T4-5EL- <vNHSrN^NYrN^I'NY'N^ll'NY'N^l'NYrN^l'NH2n0'0 1 0'0 10I YTV< VH;F NA k< HO-HOJ 8) L is 5T4-6EL;DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;j?no 9 p _____ — - Hc / yy y^N 05) L is 5T4-4EL; 7 HO-V'OH UyNVyNH H / - / I]HO<_OH0^~NH o H ° H 9 H 9 H ° < 6) L is 5T4-5EL;<s-NH CNx>1'N^NjkN^, NjilN^rN^N^fNxA0H7) L is 5T4-5EL- 0 °H°H°H°H°f niX VH;HOVo J 8) L is 5T4-6EL;DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; o 0 o< HO-J*Y°Y-°'^No YO^^N^NA^^^ II HOMOH U^ A^. NH H > 6) L is 5T4-5EL;°V°MQA-NHO H 0 H0 H 0 H O 7) L is 5T4-5EL- XX.^NH CNAYAY^NV^NV^MxJU. n 0H°H°H°H°ITTH VH;8) L is 5T4-6EL;H°VoJDAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; ° 0 3) L is 5T4-3EL; L - _ AN'^ANH4) L is 5T4-3EL- Ck VL;5) L is 5T4-4EL; A o AL 9 T < 6) L is 5T4-5EL;H0I X HN^ >NH>H0'-V-'0HUy AH O 7) L is 5T4-5EL-0HCK 0 k A 0 9VH;°XH8) L is 5T4-6EL; 9) L is 5T4-7EL; V_ o )10) L is 5T4-8EL;HO-Vo DAR11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; a o4) L is 5T4-3EL- L- _ '<r VL;%o O V55) L is 5T4-4EL;HO^Y°Y*°'^PN HN^>-NHtHO'' Y^OH O^NH | O | O | O | O 1 O S- 6) L is 5T4-5EL;OH 0^0 ^N^N^N^N^N^N^trN^'NxVN^'OH[^.. NH 0H0H□H0H0 7) L is 5T4-5EL- YTXW VH;Y. P 8) L is 5T4-6EL;<H°Vo JDAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; < °? A 4) L is 5T4-3EL- Ls<x VL;x> 5) L is 5T4-4EL; o?Ho^ o ^ONHN^^r'NHV 6) L is 5T4-5EL;HO'V'OH O^NH 0 | 0 | 0 | O 1 9 fOH 0 0 ^N^N^N^N^N^N^N^y-¥N^ANH27) L is 5T4-5EL- 0H0HOHOH0VH;xxxwV o y 8) L is 5T4-6EL;HOVo DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; X" ° o 4) L is 5T4-3EL- VL;L' —0\^0 5) L is 5T4-4EL; H0 lY°6) L is 5T4-5EL; AH0VX°YXHJNA / YH>HO- Y-'°H O-^NH! 0Ho! o, oHo°H°Y° YN^N-YN'-AN-YN-AN-YN-AN^IrN-AOH 7) L is 5T4-5EL- 0 1 0 1 0H0 1 0VH;8) L is 5T4-6EL; YJDAR / °9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;A ° o 4) L is 5T4-3EL- _ AN^^NH^-^0 S VL;0.% 5) L is 5T4-4EL;J 9no V >H06) L is 5T4-5EL;A N HN^^y'NHHO" Y"OHYyJ0YHoH0 0 0H0 f7) L is 5T4-5EL- / \.'NH 01010H010 VH; XXXN^_ J 8) L is 5T4-6EL;FDARHo^no9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;V ^ ^ 6) L is 5T4-5EL;^N^N^N^N^N^N^N^N^OH7) L is 5T4-5EL- VH;8) L is 5T4-6EL;^n -^DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; ° 0 _4) L is 5T4-3EL- VL;5) L is 5T4-4EL; J HO^°Y°\^NHN^^ A-'NH0vAA L A J J I A 6) L is 5T4-5EL;0HY A ^ 7) L is 5T4-5EL- VH;AX ANA8) L is 5T4-6EL; IH7 / 0yJ DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;° o " A_ AN^^NH 4) L is 5T4-3EL- ^0 Sex VL;%0 0 5) L is 5T4-4EL;HN^VNH1HO” V'OH O^NH 0.H> 6) L is 5T4-5EL;OH 0^0 k><NX, N-^-OH <. XX... NHH0.2=0 7) L is 5T4-5EL- VH;’ A oY P " ' 9 1 H 0HOVo 0 H YA 8) L is 5T4-6EL;H0?jDAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL;C o O_ AN^^SIH 4) L is 5T4-3EL- L - ' '" S? SCL VL;%o o 5) L is 5T4-4EL;J HO-\°Y*O'^pN HN-M'NH1A HO-V-OH W O NH 0.h> 6) L is 5T4-5EL;OH °yO ^N\Nyr-OH (^, NHHr, 7) L is 5T4-5EL- Y9X> A° O - H 0QANHoVH;V P " I 9 1 H o 8) L is 5T4-6EL;1HO\ o 0 nV' / HHO' y 9) L is 5T4-7EL;DAR 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; z °_(AN'^A 0NH X 4) L is 5T4-3EL- L—0\ VL;k)H9H00 nN,... 5) L is 5T4-4EL;H0WNHN^'NH 0°0°H°-V;OHUy o4 o,HHN\HI 6) L is 5T4-5EL;0, 0 zNCN / °H, / 0 fn, NH H o0°? i o 0° 7) L is 5T4-5EL-0-H° O0OAOV VH;\ 0 T 0 j L7 oHN. OIHOVVxO yNHH0 ) NHO y? - 8) L is 5T4-6EL;0DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL; 6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;8) L is 5T4-6EL; 9) L is 5T4-7EL; 10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- VL;5) L is 5T4-4EL;J k Y X JHO^ OH 6) L is 5T4-5EL;V f7) L is 5T4-5EL- NHHOTAAOH YVV, / ° ACHN V0VH;W H ”3$” 8) L is 5T4-6EL;O HO > / -OH 9) L is 5T4-7EL;\ -X DAR 10) L is 5T4-8EL;11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- O I O I O I O I oO^N.1O1O1O1O1O VL;o rHO 5) L is 5T4-4EL;6) L is 5T4-5EL; 7) L is 5T4-5EL- VH;o 8) L is 5T4-6EL;^ DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- O 1 o 1 o 1 o 1 oA ^ NrNA NNA NNA N N""NN NH2ZVL;„ O, N 0 0 0 0 0o Y _L5) L is 5T4-4EL;HoVr°Vl? H V - - - J HO'Y ’OH I 6) L is 5T4-5EL;A OH 0, 0HO o YrA 'NH7) L is 5T4-5EL- F'^AI'A A VH;AAoHOTA 8) L is 5T4-6EL;DAR 9) L is 5T4-7EL;10) L is 5T4-8EL; 11) L is 5T4-9; 12) L is 5T4-9EL;WSGR Docket No. 63125-725.601Conjugates Antibody (L)13) L is 5T4- 10EL;14) L is 5T4- 11EL;15) L is 5T4- 12EL;16) L is 5T4- 13EL;17) L is 5T4- 14EL;18) L is 5T4- 15EL;19) L is 5T4-16; 20) L is 5T4-17; 21) L is 5T4-18; 22) L is 5T4-19; 23) L is 5T4-20; or24) L is 5T4-21.1) L is 5T4-1EL; 2) L is 5T4-2EL; 3) L is 5T4-3EL; 4) L is 5T4-3EL- A M? t!?H9 VL;0 O NH H Q H0H o ...
Claims
1. WSGR Docket No. 63125-725.6012.CLAIMS WHAT IS CLAIMED IS:
1. A conjugate of the Formula (XX):4.L'M25.I6.S27.S28.Si.9.Y (K1)m11.
12. D Formula (XX)13.or a pharmaceutically acceptable salt thereof, wherein;14.L is a Targeting Unit, wherein the Targeting Unit is an anti-5 T4 antibody or an antigenbinding portion thereof;15.(K2-(S4)p)n16.R40is independently selected from hydrogen, Y17.
18. , and19.D is selected from a Drug unit;20.n is selected from 0 and 1;21.m is selected from 0 and 1;22.wherein at least n or m is 1;23.p is selected from 0 and 1;24.z is selected from 0 and 1;25.X is selected from CH and N;26.Y is a -0-T1and -NH-T2;27.T1IS a sugar cleavable unit;28.2 is peptide cleavable unit;29.s1IS selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C3o alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino WSGR Docket No. 63125-725.60130.acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;31.S2is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;32.53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;33.54is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;34.wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4are independently selected at each occurrence from:35.(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;36.(ii) Ci-io alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10 carbocycle and 3-to 10-membered heterocycle; and37.(iii) C3.10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6alkynyl;38.M2is a connector unit;39.K1is selected from: WSGR Docket No. 63125-725.60140.(i) a peptide unit,41.(ii) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)--S(O)2- or -P(O)(R20)2-;42.(iii) an oligosaccharide; and43.(iv) a polyether;44.K2is selected from:45.(i) a peptide unit,46.(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, -S(O)2- or -P(O)(R20)2-;47.(iii) an oligosaccharide; and48.(iv) a polyether;49.each R20is independently selected from hydrogen; and Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.12 carbocycle, and 3- to 12-membered heterocycle; and50.each R30is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3.i2carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci.10 alkyl, -Ci.10 haloalkyl, -O-C O alkyl, oxo, C3-12 carbocycle, and 3- to 12-membered heterocycle.
2. The conjugate or salt of claim 1, wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.
3. The conjugate or salt of claims 1 or 2, wherein Formula (XX) is represented byL'M253.S 1254.S255.(K,1)m56.°Y°57.D Formula (XXI) or WSGR Docket No. 63125-725.60158.L'M259.l60.S361.s262.T (K1)m63.0^ / 065.
66. D Formula (XXII)67.or a pharmaceutically acceptable salt thereof.
4. The conjugate or salt of any one of claims 1 to 3, wherein Formula (XX) is represented by70.
71. Formula (XXIII)72.or a pharmaceutically acceptable salt thereof.
5. The conjugate or salt of any one of claims 1 to 3, wherein Formula (XX) is represented by74.(K2-(S4)D) M275.l76.S377.S278.k,79.(K1)m81.
82. D Formula (A)83.or a pharmaceutically acceptable salt thereof.
6. The conjugate or salt of any one of claims 1 to 3, wherein Formula (A) is represented by86.
87. D Formula (A-l)88.or a pharmaceutically acceptable salt thereof.
7. The conjugate or salt of any one of claims 1 to 6, wherein S1is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -WSGR Docket No. 63125-725.60190.N(R20)S(O)2- - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0- -S-, -S(0)-, -S(0)2- or -P(O)(R20)2-.
8. The conjugate or salt of any one of claims 1 to 7, where S1is selected from: (i) an optionally substituted Ce-Cio alkylene wherein one or more alkylene units of the Ce-Cio alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, or -C(O)-.
9. The conjugate or salt of any one of claims 1 to 8, wherein S1is a branched alkylene.
10. The conjugate or salt of any one of claims 1 to 9, wherein S1is represented by NH HN11. The conjugate or salt of any one of claims 1 to 10, wherein S1is represented by95.NH HN97.
98. O O12. The conjugate or salt of any one of claims 1 to 11, wherein S2is selected from: (i) an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, and -C(O)-.
13. The conjugate or salt of any one of claims 1 to 12, wherein S2is a linear alkylene.
14. The conjugate or salt of any one of claims 1 to 13, wherein S2is represented by101.NH103.
104. WSGR Docket No. 63125-725.60115. The conjugate or salt of any one of claims 1 to 14, wherein S2is represented by107.
16. The conjugate or salt of any one of claims 1 to 15, wherein M2is selected from111.
17. The conjugate or salt of any one of claims 1 to 16, wherein M2is selected from115.
18. The conjugate or salt of any one of claims 1 to 17, wherein M118. 119.2is19. The conjugate or salt of any one of claims 1 to 17, wherein M121. 122.2is20. The conjugate or salt of any one of claims 1 to 17, wherein M124. 125.2is 21. The conjugate or salt of claim 18, wherein Formula (A) is represented by WSGR Docket No. 63125-725.601127.
128. Formula (A -2) or a pharmaceutically acceptable salt thereof.
22. The conjugate or salt of any one of claims 1 to 21, wherein X is CH.
23. The conjugate or salt of any one of claims 1 to 21, wherein X is N.
24. The conjugate or salt of any one of claims 1 to 23, wherein S3is present and is a phenylene.
25. The conjugate or salt of any one of claims 1 to 23, wherein S3is absent.
26. The conjugate or salt of any one of claims 1 to 25, wherein Formula (A) is represented by135. 137.Formula (A-7) wherein DAR is a drug to antibody ratio,138.or a pharmaceutically acceptable salt thereof.
27. The conjugate or salt of any one of claims 1 to 26, wherein Formula (A) is represented byWSGR Docket No. 63125-725.601141.
142. DAR Formula (A-8), wherein DAR is a drug to antibody ratio,143.or a pharmaceutically acceptable salt thereof.
28. The conjugate or salt of any one of claims 1 to 27, wherein each K1is selected from a peptide unit.
29. The conjugate or salt of any one of claims 1 to 28, wherein the peptide unit of K1has 1 to 50 amino acids.
30. The conjugate or salt of any one of claims 1 to 29, wherein the amino acids of K1is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine.
31. The conjugate or salt of any one of claims 1 to 30, wherein the amino acids of K1is selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and P -Alanine.
32. The conjugate or salt of any one of claims 1 to 31, wherein the peptide unit of K1has a terminus unit.
33. The conjugate or salt of any one of claims 1 to 32, wherein K1is selected from151.
152. WSGR Docket No. 63125-725.601153., and155.
156. wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.
34. The conjugate or salt of any one of claims 1 to 33, wherein K1is selected from159.
160. , wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.
35. The conjugate or salt of any one of claims 1 to 33, wherein K1is selected from163.
164. WSGR Docket No. 63125-725.601165., and167.
168. wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.
36. The conjugate or salt of any one of claims 1 to 33, wherein K1is selected from171.
172.
37. The conjugate or salt of any one of claims 1 to 33, wherein K1is selected from174.
38. The conjugate or salt of any one of claims 1 to 33, wherein K1is selected from177.w179.
180. J, wherein j is selected from 5 to 15.
39. The conjugate or salt of any one of claims 1 to 33, wherein K1is selected from183.
184. J, wherein j is selected from 3 to 8. WSGR Docket No. 63125-725.60140. The conjugate or salt of any one of claims 1 to 33, wherein K1is selected from187.
188. , wherein j is selected from 3 to 8.
41. The conjugate or salt of any one of claims 33 to 40, wherein R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10 alkyl, C2-io alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =s, =N(R30), -CN, C3.10 carbocycle and 3- to 10-membered heterocycle.
42. The conjugate or salt of any one of claims 33 to 41, wherein R6is selected from -OH, -191.N193.
43. The conjugate or salt of any one of claims 33 to 41, wherein R6is -OH.
44. The conjugate or salt of any one of claims 33 to 41, wherein R6is -NH2.197.N45. The conjugate or salt of any one of claims 33 to 41, wherein R6is199. 200.n 046. The conjugate or salt of any one of claims 1 to 32, wherein K1is selected from201.10 10 10 10202.N N H H203.N N H H205.
206. WSGR Docket No. 63125-725.601208.
209. WSGR Docket No. 63125 -725.601211.
48. The conjugate or salt of any one of claims 1 to 32, wherein K1is selected from215.
216. WSGR Docket No. 63125-725.601218.
219. WSGR Docket No. 63125-725.601220., and221.
222.
50. The conjugate or salt of any one of claims 1 to 32, wherein K1is224.
51. The conjugate or salt of any one of claims 1 to 32, wherein K1is selected from228.
52. The conjugate or salt of any one of claims 1 to 32, wherein K1is53. The conjugate or salt of any one of claims 1 to 32, wherein K1is233.
234. WSGR Docket No. 63125-725.60154. The conjugate or salt of any one of claims 1 to 32, wherein K1is selected from237.
55. The conjugate or salt of any one of claims 1 to 32, wherein K1is240. 241.0 556. The conjugate or salt of any one of claims 1 to 32, wherein K1is243.
244.
57. The conjugate or salt of any one of claims 1 to 32, wherein K1is selected from246.
58. The conjugate or salt of any one of claims 1 to 32, wherein249.
250. K1is59. The conjugate or salt of any one of claims 1 to 32, wherein252.
253. K1is60. The conjugate or salt of any one of claims 1 to 32, wherein255.
256. K1is 61. The conjugate or salt of any one of claims 1 to 32, wherein K1is258.
62. The conjugate or salt of any one of claims 1 to 32, wherein K1is262.
263. WSGR Docket No. 63125-725.60163. The conjugate or salt of any one of claims 1 to 32, wherein K1is266.
64. The conjugate or salt of any one of claims 1 to 32, wherein K1is269.AN- "270.
65. The conjugate or salt of any one of claims 1 to 10, wherein S1is represented by273.H HN N275.
276. O66. The conjugate or salt of claim 65, wherein eachK1is selected from: an oligosaccharide.
67. The conjugate or salt of claim 66, wherein each K1is selected from:278.OH280.
281.
368. The conjugate or salt of claim 1, wherein Formula (A) is represented by284. 285.DFormula (A-3)286.or a pharmaceutically acceptable salt thereof.
69. The conjugate or salt of claim 1, wherein Formula (A) is represented byWSGR Docket No. 63125-725.601288.I289.s3290.(X r>292.
293. Formula (A-4)294.or a pharmaceutically acceptable salt thereof.
70. The conjugate or salt of any one of claims 68 to 69, wherein S1is selected from: (i) an optionally substituted Ci-C2alkylene wherein one or more alkylene units of the Ci-C2alkylene are optionally and independently replaced by -N(R20)-.
71. The conjugate or salt of any one of claims 68 to 70, wherein S1is represented by N298.
72. The conjugate or salt of any one of claims 68 to 71, wherein S2is selected from: (i) an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, and -C(O)-.
73. The conjugate or salt of any one of claims 68 to 72, wherein S2is a linear alkylene.
74. The conjugate or salt of any one of claims 68 to 73, wherein S2is represented by303.N305.
306. O75. The conjugate or salt of any one of claims 68 to 74, wherein S'-S2is represented by308.N309.N311.
76. The conjugate or salt of any one of claims 68 to 75, wherein S3is present and is a phenylene.
77. The conjugate or salt of any one of claims 68 to 75, wherein S3is absent.WSGR Docket No. 63125-725.60178. The conjugate or salt of any one of claims 68 to 77, wherein M2is selected from317.
318.
80. The conjugate or salt of any one of claims 68 to 78, wherein M2is selected from320.
81. The conjugate or salt of any one of claims 68 to 78, wherein M323. 324.
282. The conjugate or salt of any one of claims 68 to 78, wherein M326. 327.
283. The conjugate or salt of any one of claims 68 to 78, wherein328.
329. M2is WSGR Docket No. 63125-725.60184. The conjugate or salt of any one of claims 68 to 81, wherein S1-S2-M2-L is represented332.
85. The conjugate or salt of any one of claims 68 to 81, wherein Formula (A) is represented by336.
337. Formula (A-5) or a pharmaceutically acceptable salt thereof.
86. The conjugate or salt of any one of claims 68 to 81, wherein Formula (A) is represented by340.
341. Formula (A-6) or a pharmaceutically acceptable salt thereof.
87. The conjugate or salt of any one of claims 68 to 86, wherein p is 1.
88. The conjugate or salt of any one of claims 68 to 87, wherein S4is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, or -C(O)-.
89. The conjugate or salt of any one of claims 68 to 88, wherein S4is selected from: (i) an optionally substituted C1-C5 alkylene wherein one or more alkylene units of the C1-C5 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -O-, or -C(O)-.
90. The conjugate or salt of any one of claims 68 to 89, wherein S4is selected from: (i) an optionally substituted C1-C3 alkylene wherein one or more alkylene units of the Ci-C5alkylene are optionally and independently replaced by -N(H)-, -N(CH3)-, -O-, or -C(O)-.WSGR Docket No. 63125-725.601346.o 91. The conjugate or salt of any one of claims 68 to 90, wherein S4is selected from347.
349.
92. The conjugate or salt of any one of claims 68 to 90, wherein S4is352.
93. The conjugate or salt of any one of claims 68 to 90, wherein S4is355.
94. The conjugate or salt of any one of claims 68 to 90, wherein S4is358.
359.
95. The conjugate or salt of any one of claims 68 to 94, wherein each K2is selected from a peptide unit.
96. The conjugate or salt of any one of claims 68 to 95, wherein the peptide unit of K2has 1 to 50 amino acids.
97. The conjugate or salt of claim 96, wherein the amino acids of K2is selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine.
98. The conjugate or salt of claim 97, wherein the amino acids of K2is selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and P -Alanine.
99. The conjugate or salt of any one of claims 68 to 98, wherein the peptide unit of K2has a terminus unit.
100. The conjugate or salt of any one of claims 68 to 99, wherein K2is selected from366.
367. WSGR Docket No. 63125-725.601368., and370.
101. The conjugate or salt of any one of claims 68 to 99, wherein K2is selected from373., and375.
376. wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.
102. The conjugate or salt of any one of claims 68 to 98, wherein K2is selected from379.
380. WSGR Docket No. 63125-725.601382.
383. , wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.
103. The conjugate or salt of any one of claims 100 to 102, wherein R6is selected from -OR7and -NHR7, wherein R7is selected from hydrogen; C1-10 alkyl, C2-io alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =s, =N(R30), -CN, C3.10 carbocycle and 3- to 10-membered heterocycle.
104. The conjugate or salt of any one of claims 100 to 103, wherein R6is selected from -OH, - z386.N387.
388. H2, and H O0H.
105. The conjugate or salt of any one of claims 100 to 104, wherein R6is -OH.
106. The conjugate or salt of any one of claims 100 to 104, wherein R6is -NH2.391.Z z\ '°392.LJ107. The conjugate or salt of any one of claims 100 to 104, wherein R6is0 / S'0H108. The conjugate or salt of any one of claims 68 to 99, wherein K2is selected from395.
396. WSGR Docket No. 63125-725.601398.
399. WSGR Docket No. 63125-725.601401.
402. WSGR Docket No. 63125-725.601111. The conjugate or salt of any one of claims 68 to 99, wherein K2is404.° s°406.
407. 6'0H112. The conjugate or salt of any one of claims 68 to 99, wherein K2is selected from410.
113. The conjugate or salt of any one of claims 68 to 99, wherein K2is114. The conjugate or salt of any one of claims 68 to 99, wherein K2is415.
115. The conjugate or salt of any one of claims 68 to 99, wherein K2is selected from419. 421.I °\ ^N^lfN^ 70H116. The conjugate or salt of any one of claims 68 to 99, wherein K2is422. 423.5117. The conjugate or salt of any one of claims 68 to 99, wherein K2is425.
118. The conjugate or salt of any one of claims 68 to 99, wherein K2is selected from429.
119. The conjugate or salt of any one of claims 68 to 99, wherein432.
433. K2is WSGR Docket No. 63125-725.601120. The conjugate or salt of any one of claims 68 to 99, wherein435.
436. K2is121. The conjugate or salt of any one of claims 68 to 99, wherein438.
439. K2is 122. The conjugate or salt of any one of claims 68 to 99, wherein K2is441.
123. The conjugate or salt of any one of claims 68 to 99, wherein K2is445.
124. The conjugate or salt of any one of claims 68 to 99, wherein K2is449.
125. The conjugate or salt of any one of claims 68 to 99, wherein K2is453.
454.
126. The conjugate or salt of any one of claims 68 to 99, wherein K2is selected from: an oligosaccharide.
127. The conjugate or salt of claim 126, wherein each K2is selected from:
457.
458. wherein k is selected from 2 to 10. WSGR Docket No. 63125-725.601128. The conjugate or salt of claim 127, wherein each K2is selected from:
461.
129. The conjugate or salt of any one of claims 1 to 128, wherein the sugar cleavable unit of T1includes a sugar.
130. The conjugate or salt of claim 129, wherein the sugar is glucuronide.465.O^OH466.H° I0HO / N / '''OX / 131. The conjugate or salt of any one of claims 1 to 130, wherein467.
468. Y isOH132. The conjugate or salt of any one of claims 1 to 128, wherein the peptide unit of T2includes one or more amino acids selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and P-Alanine.
133. The conjugate or salt of any one of claims 1 to 128, or 132, wherein the peptide unit of T2includes a dipeptide or tripeptide.
134. The conjugate or salt of claim 1 to 128, or 132 to 133, wherein the peptide unit of T2includes a dipeptide.
135. The conjugate orsaltof any one of claims 1 to 128, or 132to 134, wherein the dipeptide is selected from Val-Cit, Vai-Ala and Phe-Lys.
136. The conjugate or salt of any one of claims 1 to 128, or 132 to 135, wherein the peptide unit of T2includes a capping moiety.473.O137. The conjugate or salt of claim 136, wherein the capping moiety is475.
476. .
138. The conjugate or salt of any one of claims 1 to 128, or 132 to 137, wherein Y is479.
480. WSGR Docket No. 63125-725.601139. The conjugate or salt of any one of claims 1 to 138, wherein D is a selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand.
140. The conjugate or salt of any one of claims 1 to 138, wherein D is selected from a cytotoxic agent, camptothecin derivative, and an immune modulatory agent.
141. The conjugate or salt of any one of claims 1 to 138, wherein D is a selected from a cytotoxic agent, and an immune modulatory agent.
142. The conjugate or salt of any one of claims 1 to 138, wherein D is selected from exatecan, SN-38, MMAF, and monomethyl auristatin E (MMAE).
143. The conjugate or salt of any one of claims 1 to 138, wherein D is selected from exatecan and monomethyl auristatin E (MMAE).
144. The conjugate or salt of any one of claims 1 to 138, wherein D is MMAE.
145. The conjugate or salt of any one of claims 1 to 138, wherein D is exatecan.
146. The conjugate or salt of any one of claims 1 to 138, wherein D is490.
147. A conjugate selected from Table A, Table A-S, Table A-R, Table B, Table B-S, and Table B-R.
148. A conjugate selected from Table A, Table A-S, and Table A-R.
149. A conjugate selected from Table B, Table B-S, and Table B-R.
150. The conjugate or salt of any one of claims 1 to 149, having a DAR (drug to antibody ratio) of about 1 to about 8.
151. The conjugate or salt of any one of claims 1 to 148, having a DAR of about 4 to about 8.
152. The conjugate or salt of any one of claims 1 to 149, having a DAR of about 8.
153. A conjugate represented by the Formula (Aa) or Formula (Ab):
500.
501. Formula (Aa), WSGR Docket No. 63125-725.601503.
504. D Formula (Ab), or505.or a pharmaceutically acceptable salt thereof, wherein;506.L is a Targeting Unit, wherein the Targeting Unit is an anti-5T4 antibody or an antigenbinding portion thereof;507.D is selected from a Drug unit;508.n is selected from 0 and 1;509.m is selected from 0 and 1;510.wherein at least n or m is 1;511.p is selected from 0 and 1;512.X is selected from CH and N;513.Y is a -O-T1and -NH-T2;514.T1is a sugar cleavable unit;515.T2is peptide cleavable unit;516.S1is selected from: (i) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, — S(O)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-Ci0carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;517.S2is selected from: (i) an optionally substituted Ci-C3o alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C30alkenylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-,-S(O)-, WSGR Docket No. 63125-725.601518.— S(0)2—, or -P(O)(R20)2-; (iii) one or more amino acid(s); (iv) one ormoreN-substituted amino acid(s); (v) optionally substituted poly ether; (vi) optionally substituted C3-C10 carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene;519.53is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;520.54is selected from: (i) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the C1-C30 alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, — S(O)—, — S(O)2—, 5- to 6-membered heterocyclene, or -P(O)(R20)2-;521.wherein the optional substituents on M2, K1, K2, S1, S2, S3, and S4, are independently selected at each occurrence from:522.(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =0, =S, =N(R30), and -CN;523.(ii) Ci-io alkyl, C2-io alkenyl, C2.io alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, C3.10 carbocycle and 3-to 10-membered heterocycle; and524.(iii) C3.10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -N02, =0, =S, =N(R30), -CN, Ci.6alkyl, C2.6alkenyl, and C2-6 alkynyl;525.M2is a connector unit;526.K1is selected from:527.(i) a peptide unit,528.(ii) an optionally substituted C1-C30 alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2-, - S(O)2N(R20)-, -0-, -C(0)-, -0C(0)-, -C(0)0-, -S-,-S(O)-, -S(0)2- or -P(O)(R20)2-;529.(iii) an oligosaccharide; and530.(iv) a polyether;531.K2is selected from:532.(i) a peptide unit, WSGR Docket No. 63125-725.601533.(ii) an optionally substituted Ci-C30alkylene wherein one or more alkylene units of the Ci-C30alkylene are optionally and independently replaced by -N(R20)-, -N(R20)C(O)-, -C(O)N(R20)-, -N(R20)S(O)2- - S(O)2N(R20)-, -O-, -C(O)-, -OC(O)-, -C(O)O- -S-, -S(O)--S(O)2- or -P(O)(R20)2-;534.(iii) an oligosaccharide; and535.(iv) a polyether;536.each R20is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3.i2carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6 alkyl)2, Ci.10 alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.i2 carbocycle, and 3- to 12-membered heterocycle; and537.each R30is independently selected from hydrogen; and Ci.6alkyl, C2.6alkenyl, C2.6alkynyl, C3.i2 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(CI-6alkyl)2, Cuo alkyl, -Cuo haloalkyl, -O-C O alkyl, oxo, C3.i2carbocycle, and 3- to 12-membered heterocycle.
154. The conjugate or salt of claim 153, wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K1is a polysarcosine, the polysarcosine contains 2-9 sarcosines or 13-30 sarcosines.
155. The conjugate or salt of any one of claims 1 to 154, wherein the antibody or portion thereof comprises a heavy chain CDR (HCDR) 1 -3 and a light chain CDR (LCDR) 1 -3 comprising SEQ ID NOs:65, 70, 75, 78, 81, and 84, respectively.
156. The conjugate or salt of any one of claims 1 to 154, wherein the antibody or portion thereof comprises a heavy chain CDR (HCDR) 1 -3 and a light chain CDR (LCDR) 1 -3 comprising SEQ ID NOs:67, 72, 76, 78, 81, and 84, respectively.
157. The conjugate or salt of claims 155 or 156, wherein the antibody or portion thereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VL) comprising SEQ ID NOs:20 and 21, respectively.
158. The conjugate or salt of any one of claims 1 to 154, wherein the antibody or portion thereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VHand the VLcomprise:543.SEQ ID NOs:4 and 5, respectively;544.SEQ ID NOs:6 and 7, respectively;545.SEQ ID NOs:8 and 9, respectively;546.SEQ ID NOs:10 and 11, respectively; WSGR Docket No. 63125-725.601547.SEQ ID NOs:10 and 12, respectively;548.SEQ ID N0s:13 and 14, respectively;549.SEQ ID N0s:15 and 17, respectively;550.SEQ ID N0s:16 and 17, respectively;551.SEQ ID N0s:18 and 19, respectively;552.SEQ ID NOs:20 and 21, respectively;553.SEQ ID NOs:22 and 23, respectively;554.SEQ ID NOs:24 and 25, respectively;555.SEQ ID NOs:26 and 27, respectively;556.SEQ ID NOs:28 and 29, respectively;557.SEQ ID NOs:30 and 31, respectively;558.SEQ ID NOs:32 and 33, respectively;559.SEQ ID NOs:34 and 35, respectively;560.SEQ ID NOs:36 and 37, respectively;561.SEQ ID NOs:38 and 39, respectively;562.SEQ ID NOs:40 and 41, respectively;563.SEQ ID NOs:42 and 43, respectively;564.SEQ ID NOs:44 and 45, respectively; or565.SEQ ID NOs:46 and 47, respectively..
159. The conjugate or salt of any one of claims 1 to 158, wherein the antibody comprises a human IgGl constant region.
160. The conjugate or salt of claim 159, wherein the human IgGi constant region comprises SEQ ID NO:1, optionally without the C-terminal lysine.
161. The conjugate or salt of claim 159, wherein the human IgGi constant region comprises SEQ ID NO:2, optionally without the C-terminal lysine.
162. The conjugate or salt of any one of claims 1 to 161, wherein the antibody comprises a human light chain constant region that comprises SEQ ID NO: 3.
163. The conjugate or salt of any one of claims 1 to 154, wherein the antibody is selected from 5T4-1EL, 5T4-2EL, 5T4-3EL, 5T4-3EL-VL, 5T4-4EL, 5T4-5EL, 5T4-5EL-VH, 5T4-6EL, 5T4-7EL, 5T4-8EL, 5T4-9, 5T4-9EL, 5T4-10EL, 5T4-11EL, 5T4-12EL, 5T4-13EL, 5T4-14EL, 5T4-15EL, 5T4-16, 5T4-17, 5T4-18, 5T4-19, 5T4-20, and 5T4-21.
164. The conjugate or salt of any one of claims 1 to 154, wherein the antibody or antigenbinding portion comprises a heavy (HC) and a light chain (LC) comprising572.SEQ ID NOs:l and 3, respectively or573.SEQ ID NOs:2 and 3, respectively. WSGR Docket No. 63125-725.601165. The conjugate or salt of claim 164, wherein the antibody or portion thereof comprises a heavy chain CDR (HCDR) 1 -3 and a light chain CDR (LCDR) 1 -3 comprising SEQ ID NOs:65, 70, 75, 78, 81, and 84, respectively.
166. The conjugate or salt of any one of claims 1 to 154, wherein the antibody or portion thereof comprises a heavy chain CDR (HCDR) 1 -3 and a light chain CDR (LCDR) 1 -3 comprising SEQ ID NOs:67, 72, 76, 78, 81, and 84, respectively.
167. A pharmaceutical composition comprising a conjugate of any one of claims 1 to 166 and a pharmaceutically acceptable excipient.
168. A method of treating a subject with a disease or disorder, comprising administering to the subject in need thereof a conjugate of any one of claims 1 to 166 or a pharmaceutical composition of claim 167.
169. The method of claim 168, wherein the disease or disorder is a cancer.
170. A method of treating a subject with a cancer, comprising administering to the subject in need thereof a conjugate of any one of claims 1 to 166 or a pharmaceutical composition of claim 167.
171. A method of treating a subject with a 5T4-positive cancer, comprising administering to the subject in need thereof a conjugate of any one of claims 1 to 166 or a pharmaceutical composition of claim 167.
172. The method of any one of claims 169 to 171, wherein the cancer is selected from: melanoma, skin basal cell cancer, glioblastoma, glioma, gliosarcoma, astrocytoma, meningioma, neuroblastoma, adrenocortical cancer, head and neck cancer (e.g., cancer of the head, neck, nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, and / or salivary glands, and paragangliomas), oral cancer, salivary gland cancer, nasopharyngeal cancer, breast cancer (e.g., triple negative breast cancer), lung cancer (e.g., non-small cell lung cancer (NSCLC), small cell lung cancer, or squamous cell lung cancer), esophageal cancer, gastroesophageal junction cancer, gastric cancer, gastrointestinal cancer, primary peritoneal cancer, liver cancer, hepatocellular carcinoma, gallbladder cancer, biliary tract cancer, cholangiocarcinoma, colon cancer, rectal cancer, colorectal carcinoma, ovarian cancer, fallopian tube cancer, bladder cancer, upper urinary tract cancer, urothelial cancer, renal cell carcinoma, kidney cancer, genitourinary cancer, cervical cancer, testicular cancer, prostate cancer, fibrosarcoma, liposarcoma, rhabdomyosarcoma (e.g., embryonal rhabdomyosarcoma), leiomyosarcoma, neurofibrosarcoma, synovial sarcoma, liposarcoma, alveolar soft part sarcoma, osteosarcoma, histiocytoma (e.g., malignant fibrous histiocytoma), pancreatic cancer, endometrial cancer, cancer of the appendix, thyroid cancer, advanced Merkel cell cancer, multiple myeloma, sarcomas, choriocarcinoma, leukemia (e.g., erythroleukemia, acuteWSGR Docket No. 63125-725.601582.lymphoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, acute myeloid leukemia, acute myelogenous leukemia, chronic myeloid leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, or mast cell leukemia), lymphoma (e.g., small lymphocytic lymphoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, non -Hodgkin’s lymphoma, diffuse large B cell lymphoma, lymphoplasmacytoid lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, T-cell anaplastic large cell lymphoma, follicular lymphoma, monocytic lymphoma, or HTLV-associated T cell leukemia / lymphoma), or mesothelioma. In certain embodiments, the cancer is selected from the group consisting of head and neck cancer, bone cancer (e.g., osteosarcoma), Ewing sarcoma, squamous cell carcinoma, lung cancer (e.g., non-small cell lung cancer or small cell lung cancer), kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, cervical cancer, pancreatic cancer, breast cancer (e.g., triple negative breast cancer), melanoma, liver cancer, bladder cancer, stomach cancer, esophageal cancer, and chronic myelogenous leukemia. In particular embodiments, the cancer is selected from the group consisting of head and neck cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, hepatic cancer, pancreatic cancer, colorectal cancer, breast cancer, endometrial cancer, ovarian cancer, soft-tissue sarcoma, bladder cancer, prostate cancer, renal cancer, and melanoma.
173. The method of any one of claims 169 to 171, wherein the cancer is selected from cell lymphoma, non-small cell lung cancer, large-cell lung cancer, breast cancer, and small-cell lung cancer.
174. The method of any one of claims 169 to 171, wherein the cancer is cell lymphoma.
175. The method of any one of claims 169 to 171, wherein the cancer is non-small cell lung cancer.
176. The method of any one of claims 169 to 171, wherein the cancer is large-cell lung cancer.
177. The method of any one of claims 169 to 171, wherein the cancer is breast cancer.
178. The method of any one of claims 169 to 171, wherein the cancer is small-cell lung cancer.
179. Use of a conjugate, for treating a subject with a disease or disorder, comprising administering to the subject in need thereof a conjugate of any one of claims 1 to 166 or a pharmaceutical composition of claim 167.
Citation Information
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