received by the International Bureau on 04 December 2017 (04.12.2017)

1. An isolated anti-B7H3 antibody wherein the antibody comprises a heavy chain variable region comprising

a CDR1 having the amino acid sequence of SEQ ID NO: 10, SEQ ID NO: 33, or SEQ ID

NO: 25;

a CDR2 having the amino acid sequence of SEQ ID NO: 140, SEQ ID NO: 34, SEQ ID NO:

11, or SEQ ID NO: 26;

a CDR3 having the amino acid sequence of SEQ ID NO: 12, SEQ ID NO: 35, SEQ ID NO:

12, or SEQ ID NO: 27; and

a light chain variable region comprising

a CDR1 having the amino acid sequence of SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 37, SEQ ID NO: 14, or SEQ ID NO: 29;

a CDR2 having the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 38, or SEQ ID

NO: 30;

a CDR3 having the amino acid sequence of SEQ ID NO: 15, SEQ ID NO: 39, or SEQ ID

NO: 31.

2. The antibody according to claim 1, wherein the antibody further comprises a human acceptor

framework, said human acceptor framework comprising an amino acid sequence selected from the group consisting of SEQ ID Nos: 155, 156, 157, 158, 164, 165, 166, and 167.

3. The anti-hB7-H3 antibody according to claim 1, wherein the antibody comprises a heavy chain variable domain comprising an amino acid sequence set forth in SEQ ID NO: 139 or 147 and a light chain variable domain comprising an amino acid sequence set forth in SEQ ID NO: 135, SEQ ID NO: 137, or SEQ ID NO: 144.

4. The anti-hB7-H3 antibody according to claim 1, wherein the antibody comprises a sequence set selected from the group consisting of

a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 168 and a light chain comprising the amino acid sequence of SEQ ID NO: 169;

b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 170 and a light chain comprising the amino acid sequence of SEQ ID NO: 171; and

c) a heavy chain comprising the amino acid sequence of SEQ ID NO: 172 and a light chain comprising the amino acid sequence of SEQ ID NO: 173.

5. A pharmaceutical composition comprising the anti-hB7-H3 antibody of any one of claims 1-4, and a pharmaceutically acceptable carrier.

6. An anti-hB7-H3 Antibody Drug Conjugate (ADC) comprising an anti-hB7-H3 antibody of any one of claims 1 -4 conjugated to a drug via a linker.

7. An anti-hB7-H3 antibody drug conjugate (ADC) comprising a drug linked to an anti-human B7-H3 (hB7-H3) antibody via a linker, wherein the drug is a Bcl-xL inhibitor according to structural formula (Ila):

and is optionally substituted with one or more substituents independently selected from halo, cyano, methyl, and halomethyl;

Z¹ is selected from N, CH and C-CN;

Z² is selected from NH, CH₂, O, S, S(O), and S(0)₂;

R¹ is selected from methyl, chloro, and cyano;

R² is selected from hydrogen, methyl, chloro, and cyano;

R⁴ is hydrogen, wherein the R⁴ Ci_4 alkanyl, C₂-4 alkenyl, C₂-4 alkynyl, C^ haloalkyl and C^ hydroxyalkyl are optionally substituted with one or more substituents independently selected from OCH₃, OCH₂CH₂OCH₃, and OCH₂CH₂NHCH₃;

R^10a, R^10b, and R^10c are each, independently of one another, selected from hydrogen, halo, Ci₆ alkanyl, C₂_6 alkenyl, C₂_6 alkynyl, and Ci_₆ haloalkyl;

R^lla and R^nb are each, independently of one another, selected from hydrogen, methyl, ethyl, halomethyl, hydroxyl, methoxy, halo, CN and SCH₃;

n is 0, 1, 2 or 3; and

# represents a point of attachment to a linker.

8. The ADC of claim 7, which is a compound according to structural formula (I): (I) ( D L LK-)-Ab wherein:

D is the Bcl-xL inhibitor drug of formula (Ila);

L is the linker;

Ab is the anti-hB7-H3 antibody;

LK represents a covalent linkage linking the linker (L) to the anti-hB7-H3 antibody (Ab); and m is an integer ranging from 1 to 20.

9. The ADC of claim 8 in which:

D is the Bcl-xL inhibitor selected from the group consisting of the following compounds modified in that the hydrogen corresponding to the # position of structural formula (Ila) is not present forming a monoradical:

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-[l-({3,5- dimethyl-7- [2-(methylamino)ethoxy] tricyclo [3.3.1. l³'⁷]dec- 1 -yl} methyl)-5 -methyl- ΙΗ-pyr azol-4- yl]pyridine-2-carboxylic acid;

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-(l- { [(lr,3R,5S,7s)-3,5-dimemyl-7-(2-{2-[2-(memylamino)ethoxy]emoxy}emoxy)tricyclo[3.3.1.1³'⁷]dec-l- yl]methyl}-5-methyl-lH-pyrazol-4-yl)pyridine-2-carboxylic acid;

3-(l-{ [3-(2-aminoemoxy)-5 -dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl]methyl}-5-methyl-lH- pyrazol-4-yl)-6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]pyridine-2-carboxylic acid;

3-[l-({3-[2-(2-aminoethoxy)ethoxy]-5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl}methyl)-5- methyl-lH-pyrazol-4-yl]-6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]pyrM 2-carboxylic acid;

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-{ l-[(3-{2-[(2- methoxyethyl)amino]emoxy}-5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl)memyl]-5-methyl-lH-pyrazol-4- yl}pyridine-2-carboxylic acid;

3-(l-{ [3-(2-aminoethoxy)-5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl]methyl}-5-methyl-lH- pyrazol-4-yl)-6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-5-fluoro-3,4-dihydroisoquinolin-2(lH)-yl]pyridine-2- carboxylic acid;

3-(l-{ [3-(2-aminoemoxy)-5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl]methyl}-5-methyl-lH- pyrazol-4-yl)-6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-6-fluoro-3,4-dihydroisoquinolin-2(lH)-yl]pyridine-2- carboxylic acid; and 3-(l-{ [3-(2-aminoemoxy)-5,7-dimethyltricycto^

pyrazol-4-yl)-6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-7-fluoro-3,4-dihydroisoquinolin-2(lH)-yl]pyridin carboxylic acid;

L is selected from the group consisting of linkers IVa.l-IVa.8, IVb.l-IVb.19, IVc.l-IVc.7, IVd.l- IVd.4, Va.l-Va.12, Vb.l-Vb.lO, Vc.l-Vc.l l, Vd.l-Vd.6, Ve.l-Ve.2, Vla.l, VIc.l-Vlc.2, VId.l-VId.4, VIIa.l-VIIa.4, VIIb.l-VIIb.8, VIIc.l-VIIc.6 wherein each linker has reacted with the anti-hB7-H3 antibody, Ab, forming a covalent attachment;

LK is thioether; and

m is an integer ranging from 1 to 8.

10. The ADC of any one of claims 7-9, wherein the anti-hB7-H3 antibody comprises

a heavy chain CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 12 or SEQ ID NO: 35,

a heavy chain CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 140 or SEQ ID NO: 34, and

a heavy chain CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 33;

a light chain CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 15 or SEQ ID NO: 39,

a light chain CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 7 or SEQ ID NO: 38, and

a light chain CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 136, 138, or SEQ ID NO: 37.

11. The ADC of any one of claims 7-9, wherein the antibody comprises

a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 139 or SEQ ID NO: 147, and

a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 135, SEQ ID NO: 137 or SEQ ID NO: 144.

12. A pharmaceutical composition comprising an effective amount of an ADC according to any one of claims 7-11, and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising an ADC mixture comprising a plurality of the ADC of any one of claims 7-1, and a pharmaceutically acceptable carrier.

14. A method for treating cancer, comprising administering a therapeutically effective amount of the ADC of any one of claims 7-13 to a subject in need thereof.

15. A method for inhibiting or decreasing solid tumor growth in a subject having a solid tumor, said method comprising administering an effective amount of the ADC of any one of claims 7-13 to the subject having the solid tumor, such that the solid tumor growth is inhibited or decreased.

16. The method of any one of claims 14-15, wherein the ADC is administered in combination with an additional agent or an additional therapy.

17. A process for the preparation of an ADC according to claim 8, wherein

Ab is the hB7-H3 antibody, wherein the hB7-H3 antibody comprises the heavy and light chain CDRs of huAb5v2.5, huAb5v2.6, of huAbl3vl ; the process comprising:

treating an antibody in an aqueous solution with an effective amount of a disulfide reducing agent at 30-40 °C for at least 15 minutes, and then cooling the antibody solution to 20-27 °C;

adding to the reduced antibody solution a solution of water/dimethyl sulfoxide comprising a synthon selected from the group of 2.1 to 2.63 (Table B);

adjusting the pH of the solution to a pH of 7.5 to 8.5; and

allowing the reaction to run for 48 to 80 hours to form the ADC;

wherein the mass is shifted by 18 + 2 amu for each hydrolysis of a succinimide to a succinamide as measured by electron spray mass spectrometry; and

wherein the ADC is optionally purified by hydrophobic interaction chromatography.

18. An ADC of any one of claims 7-13, formed by contacting an antibody that binds a hB7-H3 cell surface receptor or tumor associated antigen expressed on a tumor cell with a drug-linker synthon under conditions in which the synthon covalently links to the antibody through a maleimide moiety as shown in formulae (lid) and (He),

wherein D is the Bcl-xL inhibitor drug of formula (Ila) or (lib); and L¹ is the portion of the linker not formed from the maleimide upon attachment of the synthon to the antibody; and wherein the drug-linker synthon is selected from the list below: N-[19-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)- 17-oxo-4,7, 10, 13-tetraoxa-16-azanonadecan-l-oyl]- L-valyl-N-{4-[({ [2-({ 3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl] (methyl) carbamoyl}oxy)methyl]phenyl}-N⁵-carbamoyl-L-ornithinamide;

N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]-L-valyl-N-{4-[({ [2-({3-[(4-{6-[8-(l,3- benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-memyl-lH pyrazol- 1 -yl)methyl] -5,7-dimethyltricyclo[3.3.1.1³'⁷]dec- 1 - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]phenyl}-N⁵-carbamoyl-L-ornithin amide;

N-[19-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)- 17-oxo-4,7, 10, 13-tetraoxa-16-azanonadecan-l-oyl]- L-alanyl-N-{4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl }oxy)ethyl] (methyl)carbamoyl }oxy) methyl]phenyl } -L-alaninamide;

N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]-L-alanyl-N-{4-[({ [2-({3-[(4-{6-[8-(l,3- benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl-lH- pyrazol- 1 -yl)methyl] -5,7-dimethyltricyclo[3.3.1.1³'⁷]dec- 1 - yl }oxy)ethyl] (methyl)carbamoyl }oxy)methyl]phenyl } -L-alaninamide;

N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]-L-valyl-N-{4-[12-({ (ls,3s)-3-[(4-{6-[8-(l,3- benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl-lH- pyrazol- l-yl)methyl]tricyclo[3.3. l. l³'⁷]dec-l-yl}oxy)-4-methyl-3-oxo-2,7,10-trioxa-4-azadodec-l- yl]phenyl}-N⁵-carbamoyl-L-ornithinamide;

N-[19-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)- 17-oxo-4,7, 10, 13-tetraoxa-16-azanonadecan-l-oyl]- L-valyl-N-{4-[12-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-l-yl)methyl]tricyclo[3.3. l.l³'⁷]dec-l-yl}oxy)-4-methyl-3-oxo- 2,7,10-trioxa-4-azadodec-l-yl]phenyl}-N⁵-carbamoyl-L-ornithinamide;

N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]-L-valyl-N-{4-[12-({ 3-[(4-{6-[8-(l,3- benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl-lH- pyrazol- l-yl)methyl]-5,7-dimethyltricyclo[3.3. l .l³'⁷]dec-l-yl}oxy)-4-methyl-3-oxo-2,7,10-trioxa-4- azadodec-l-yl]phenyl}-N⁵-carbamoyl-L-ornithin amide;

N-({2-[2-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)ethoxy]ethoxy}acetyl)-L-valyl-N-{4-[12-({ 3-[(4- {6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5- methyl-lH-pyrazol-l-yl)methyl]-5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl}oxy)-4-methyl-3-oxo-2,7,10- trioxa-4-azadodec-l-yl]phenyl}-N⁵-carbamoyl-L-ornithinamide;

N-[3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)propanoyl]-L-valyl-N-{4-[({ [2-({3-[(4-{6-[8-(l,3- benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl-lH- pyrazol- 1 -yl)methyl] -5,7-dimethyltricyclo[3.3.1.1³'⁷]dec- 1 - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]phenyl}-N⁵-carbamoyl-L-ornithin amide; N-[3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)propanoyl]-L-alanyl-N-{4-[({ [2-({3-[(4-{6-[8-(l,3- benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2( 1 H)-yl] -2-carboxypyridin-3-yl } -5 -methyl- 1H- pyrazol- 1 -yl)methyl] -5,7-dimethyltricyclo[3.3.1.1³'⁷]dec- 1 - yl }oxy)ethyl] (methyl)carbamoyl }oxy)methyl]phenyl } -L-alaninamide;

N-[(2R)-4-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)-2-sulfobutanoyl]-L-valyl-N-{4-[({ [2-({3-[(4-{6- [8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl- lH-pyrazol- 1 -yl)methyl] -5,7-dimethyltricyclo [3.3.1. l³'⁷]dec- 1 - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]phenyl}-N⁵-carbamoyl-L-ornithin amide;

N-[(2S)-4-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)-2-sulfobutanoyl]-L-valyl-N-{4-[({ [2-({3-[(4-{6- [8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl- lH-pyrazol- 1 -yl)methyl] -5,7-dimethyltricyclo [3.3.1. l³'⁷]dec- 1 - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]phenyl}-N⁵-carbamoyl-L-ornithin amide;

N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]-3-sulfo-L-alanyl-L-valyl-N-{4-[({ [2-({3-[(4- {6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5- methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl } oxy)ethyl] carbamoyl } oxy) methyl] phenyl } -L-alaninamide;

4-[(lE)-3-({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl }oxy)ethyl] (methyl)carbamoyl }oxy)prop- 1 -en- 1 -yl] -2-({N- [6-(2,5 -dioxo-2,5 -dihydro- 1 H-pyrrol- 1 - yl)hexanoyl] -beta-alanyl } amino)phenyl beta-D-glucopyranosiduronic acid;

4-{(lE)-3-[({2-[2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)- yl] -2-carboxypyridin-3 -yl } -5 -methyl- 1 H-pyrazol- 1 -yl) methyl] -5,7 -dimethyltricyclo [3.3.1.1^3,7] dec- 1 - yl }oxy)ethoxy] ethyl } carbamoyl)oxy]prop- 1 -en- 1 -yl} -2-({ N- [3-(2,5 -dioxo-2,5 -dihydro- 1 H-pyrrol- 1 - yl)propanoyl] -beta-alanyl } amino)phenyl beta-D-glucopyranosiduronic acid;

4-{(lE)-3-[({2-[2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)- yl]-2-carboxypyridin-3-yl}-5-memyl-lH-pyrazol-l-yl)methyl]-5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l- yl }oxy)ethoxy] ethyl } carbamoyl)oxy]prop- 1 -en- 1 -yl} -2-({ N- [6-(2,5 -dioxo-2,5 -dihydro- 1 H-pyrrol- 1 - yl)hexanoyl] -beta-alanyl } amino)phenyl beta-D-glucopyranosiduronic acid;

4-[(lE)-14-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-l-yl)methyl]-5,7-dimethyltricyclo[3.3. l.l³'⁷]dec-l-yl}oxy)-6- methyl-5-oxo-4,9, 12-trioxa-6-azatetradec-l -en- 1 -yl]-2-({N-[6-(2,5-dioxo-2,5-dihydro- lH-pyrrol- 1 - yl)hexanoyl] -beta-alanyl } amino)phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-3-[2-(2-{ [6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)hexanoyl]amino}ethoxy)ethoxy]phenyl beta-D-glucopyranosiduronic acid; 4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)emyl](methyl)carbamoyl}oxy)methyl]-3-[2-(2-{ [3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanoyl] amino } ethoxy)ethoxy]phenyl beta-D-glucopyranosiduronic acid;

6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-{ l-[(3-{2-[({ [3-({N-[6- (2,5 -dioxo-2,5 -dihydro- 1 H-pyrrol- 1 -yl)hexanoyl] -beta-alanyl } amino)-4-(beta-D- galactopyranosyloxy)benzyl]oxy}carbonyl)(memyl)amino]emoxy}-5,7-dimemyltricyclo[3.3.1.1³'⁷]dec-l- yl)methyl] -5-methyl- lH-pyrazol-4-yl}pyridine-2-carboxylic acid;

2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-[2-(2-{ [6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)hexanoyl]amino}ethoxy)ethoxy]phenyl beta-D-glucopyranosiduronic acid;

2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl]carbamoyl}oxy)methyl]-5-[2-(2-{ [3-(2,5 -dioxo-2,5 -dihydro- lH-pyrrol-1- yl)propanoyl] amino } ethoxy)ethoxy]phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-3-(3-{ [6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)hexanoyl] amino }propoxy)phenyl beta-D-glucopyranosiduronic acid;

l-0-({4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-2-[2-(2-{ [6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)hexanoyl]amino}ethoxy)ethoxy]phenyl}carbamoyl)-beta-D-glucopyranuronic acid;

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-(l-{ [3-(2-{ [({3-[(N-{ [2- ({N-[19-(2,5 -dioxo-2,5 -dihydro- lH-pyrrol-l-yl)- 17-oxo-4,7, 10, 13-tetraoxa-16-azanonadecan-l-oyl]-3- sulfo-D-alanyl}amino)ethoxy]acetyl}-beta-alanyl)amino]-4-(beta-D- galactopyranosyloxy)benzyl}oxy)carbonyl](memyl)amino}emoxy)-5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l- yl]methyl} -5-methyl- lH-pyrazol-4-yl)pyridine-2-carboxylic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-3-[3-({N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)hexanoyl]-3-sulfo-L-alanyl}amino)propoxy]phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-2-({N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]- beta-alanyl }amino)phenyl beta-D-glucopyranosiduronic acid; 4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)emyl](memyl)carbamoyl}oxy)methyl]-2-({N-[19-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)-17-oxo- 4,7,10,13-tetraoxa-16-azanonadecan-l-oyl]-beta-alanyl}amino)phenyl beta-D-glucopyranosiduronic acid;

4- [({ [2-({ 3 -[(4- { 6-[8-( 1 ,3 -benzothiazol-2-ylcarbamoyl)-3 ,4-dihydroisoquinolin-2( 1 H)-yl] -2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)emyl](memyl)carbamoyl}oxy)methyl]-2-({N-[4-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)butanoyl]- beta-alanyl}amino)phenyl beta-D-glucopyranosiduronic acid;

4-[12-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-l-yl)methyl]-5,7-dimethyltricyclo[3.3. l.l³'⁷]dec-l-yl}oxy)-4- methyl-3-oxo-2,7, lO-trioxa-4-azadodec- 1 -yl] -2- { [N-({ 2- [2-(2,5 -dioxo-2,5 -dihydro- 1 H-pyrrol- 1 - yl)ethoxy]ethoxy}acetyl)-beta-alanyl]amino}phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl } oxy)ethyl] (methyl)carbamoyl } oxy)methyl] -2- [(N- { 6- [(ethenylsulfonyl)amino]hexanoyl } -beta- alanyl)amino]phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-2-({N-[6-(ethenylsulfonyl)hexanoyl]-beta- alanyl}amino)phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-5-fluoro-3,4-dihydroisoquinolin-2(lH)-yl]- 2-carboxypyridin-3-yl} -5-methyl- lH-pyrazol-l-yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l- yl}oxy)ethyl]carbamoyl}oxy)methyl]-3-[2-(2-{ [3-(2,5 -dioxo-2,5 -dihydro- lH-pyrrol-1- yl)propanoyl] amino } ethoxy)ethoxy]phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl } oxy)ethyl] (methyl)carbamoyl } oxy)methyl] -3-{2-[2-({N-[3-(2,5-dioxo-2,5 -dihydro- lH-pyrrol- 1 - yl)propanoyl]-3-sulfo-L-alanyl}amino)ethoxy]ethoxy}phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl } oxy)ethyl] (methyl)carbamoyl } oxy)methyl] -3-{2-[2-({N-[6-(2,5-dioxo-2,5 -dihydro- lH-pyrrol- 1 - yl)hexanoyl]-3-sulfo-L-alanyl}amino)ethoxy]ethoxy}phenyl beta-D-glucopyranosiduronic acid;

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-{ l-[(3-{ [22-(2,5-dioxo- 2,5-dihydro-lH-pyrrol-l-yl)-3-methyl-4,20-dioxo-7,10,13,16-tetraoxa-3,19-diazadocos-l-yl]oxy}-5,7- dimemyltricyclo[3.3.1.1³'⁷]dec-l-yl)methyl]-5-methyl-lH-pyrazol-4-yl}pyridine-2-carboxylic acid; 6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-{ l-[(3-{ [28-(2,5-dioxo- 2,5-dihydro-lH-pyrrol-l-yl)-9-methyl-10,26-dioxo-3,6,13,16,19,22-hexaoxa-9,25-diazaoctacos-l-yl]oxy}- 5,7-dimethyltricyclo[3.3.1.l³'⁷]dec-l-yl)methyl]-5-methyl-lH-pyrazol-4-yl}pyridine-2-carboxylic acid;

6-[8-(l,3-benzomiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-{ l-[(3-{2-[2-(2-{ [6- (2,5 -dioxo-2,5 -dihydro- 1 H-pyrrol- 1 -yl)hexanoyl] (methyl) amino } ethoxy)ethoxy] ethoxy } -5 ,7 - dimemyltricyclo[3.3.1.1³'⁷]dec-l-yl)methyl]-5-methyl-lH-pyrazol-4-yl}pyridine-2-carboxylic acid;

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-(l-{ [3-(2-{ [4-(2,5- dioxo-2,5-dihydro- lH-pyrrol- 1 -yl)-2-sulfobutanoyl] (methyl)amino } ethoxy)-5 ,7- dimethyltricyclo [3.3.1.1^3,7] dec- 1 -yl] methyl } -5 -methyl- 1 H-pyrazol-4-yl)pyridine-2-carboxylic acid ;

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-{ l-[(3-{ [34-(2,5-dioxo- 2,5-dihydro-lH-pyrrol-l-yl)-3-methyl-4,32-dioxo-7, 10, 13, 16, 19,22,25 ,28-octaoxa-3,31-diazatetratriacont-l- yl] oxy } -5 ,7-dimethyltricyclo [3.3.1.1^3,7] dec- 1 -yl)methyl] -5 -methyl- 1 H-pyrazol-4-yl }pyridine-2-carboxylic acid;

6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-3-{ l-[(3-{ [28-(2,5-dioxo- 2,5-dihydro-lH-pyrrol-l-yl)-3-methyl-4,26-dioxo-7,10,13,16,19,22-hexaoxa-3,25-diazaoctacos-l-yl]oxy}- 5,7-dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl)methyl]-5-methyl-lH-pyrazol-4-yl}pyridine-2-carboxylic acid;

2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl } oxy)ethyl] (methyl)carbamoyl } oxy)methyl] -5 - { 2- [2-( { N- [6-(2,5 -dioxo-2,5 -dihydro- lH-pyrrol- 1 - yl)hexanoyl]-3-sulfo-L-alanyl}amino)ethoxy]ethoxy}phenyl beta-D-glucopyranosiduronic acid;

N²- [6-(2,5 -dioxo-2,5-dihydro- 1 H-pyrrol- 1 -yl)hexanoyl] -N⁶-(37-oxo- 2,5,8,11, 14,17,20,23,26,29,32,35-dodecaoxaheptatriacontan-37-yl)-L-lysyl-L-alanyl-L-valyl-N-{4-[({ [2- ({ 3- [(4- { 6- [8-( 1 ,3 -benzothiazol-2-ylcarbamoyl)-3 ,4-dihydroisoquinolin-2( lH)-yl] -2-carboxypyridin-3 -yl } - 5 -methyl- 1 H-pyrazol- 1 -yl) methyl] -5 ,7-dimethyltricyclo [3.3.1.1^3,7] dec- 1 - yl } oxy)ethyl] carbamoyl } oxy) methyl] phenyl } -L-alaninamide;

2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-[2-(2-{ [3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanoyl] amino } ethoxy)ethoxy]phenyl beta-D-glucopyranosiduronic acid;

4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-3-[3-({N-[3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanoyl]-3-sulfo-L-alanyl}amino)propoxy]phenyl beta-D-glucopyranosiduronic acid;

N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]-L-valyl-N-{4-[({ [2-({3-[(4-{6-[8-(l,3- benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl-lH- pyrazol-l-yl)methyl]-5,7-dimethyltricyclo[3.3.1.l³'⁷]dec-l-yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-3- [3-(3-sulfopropoxy)prop- 1 -yn- 1 -yl]phenyl } -L-alaninamide;

520 (6S)-2,6-anhydro-6-({2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4- dmydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-memyl-lH-pyrazol- l-yl)methyl]-5,7- dimethyltricyclo[3.3.1.l³'⁷]dec-l-yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-({N-[6-(2,5-dioxo-2,5- dihydro- lH-pyrrol- 1 -yl)hexanoyl] -L-valyl-L-alanyl } amino)phenyl }ethynyl)-L-gulonic acid;

N-[6-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)hexanoyl]-L-valyl-N-{4-[({ [2-({3-[(4-{6-[8-(l,3- benzomiazol-2-ylcarbamoyl)-3,4-dmydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-memyl-lH- pyrazol-l-yl)methyl]-5,7-dimethyltricyclo[3.3.1.l³'⁷]dec-l-yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-3- [3-(3-sulfopropoxy)propyl]phenyl}-L-alaninamide;

2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-(5-{ [3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)propanoyl] amino }pentyl)phenyl beta-D-glucopyranosiduronic acid;

2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-[16-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)-14-oxo-4,7,10- trioxa-13-azahexadec-l-yl]phenyl beta-D-glucopyranosiduronic acid;

(6S)-2,6-anhydro-6-(2-{2-[({ [2-({ 3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4- dmydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl-lH-pyrazol- l-yl)methyl]-5,7- dimethyl tricyclo [3.3.1.1^3,7] dec- 1 -yl } oxy)ethyl] (methyl)carbamoyl } oxy)methyl] -5 -( { N- [6-(2,5 -dioxo-2,5 - dihydro- lH-pyrrol- 1 -yl)hexanoyl] -L-valyl-L-alanyl } amino)ph en yl } ethyl) -L-gulonic acid;

2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-(3-{ [(2,5-dioxo-2,5-dihydro-lH-pyrrol-l- yl)acetyl] amino }propyl)phenyl D-glucopyranosiduronic acid;

2- [({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-{4-[({(3S,5S)-3-(2,5-dioxo-2,5-dihydro-lH-pyrrol-l-yl)-2- oxo-5-[(2-sulfoethoxy)methyl]pyrrolidin-l-yl}acetyl)amino]butyl}phenyl beta-D-glucopyranosiduronic acid;

3- {(3-{4-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(lH)-yl]-2- carboxypyridin-3-yl} -5-methyl- lH-pyrazol-1 -yl)methyl]-5,7-dimethyltricyclo[3.3.1. l³'⁷]dec-l - yl }oxy)ethyl] (methyl)carbamoyl }oxy)methyl] -3 -(beta-D-glucopyranuronosyloxy)phenyl Jpropyl) [(2,5- dioxo-2,5-dihydro-lH-pyrrol-l-yl)acetyl]amino}-N,N,N-trimemylpropan-l-aminium; and

(6S)-2,6-anhydro-6-[2-(2-[({ [2-({3-[(4-{6-[8-(l,3-benzothiazol-2-ylcarbamoyl)-3,4- dihydroisoquinolin-2(lH)-yl]-2-carboxypyridin-3-yl}-5-methyl-lH-pyrazol- l-yl)methyl]-5,7- dimethyltricyclo[3.3.1.1³'⁷]dec-l-yl}oxy)ethyl](methyl)carbamoyl}oxy)methyl]-5-{ [N-({(3S,5S)-3-(2,5-

521 dioxo-2,5-dihydro-lH-pyrrol-l-yl)-2-oxo-5-[(2-sulfoemoxy)^

alanyl] amino } phenyl)ethyl] -L-gulonic acid .

19. An ADC prepared by the process of claim 18.

20. An anti-human Epidermal Growth Factor Receptor (hEGFR) antibody drug conjugate (ADC) selected from the group consisting of formulae (i) or (ii):

(ii), wherein m is an integer from 1 to 6, optionally from 2 to 6; and

wherein Ab is is an anti-hB7-H3 antibody comprising a heavy chain variable region and a light chain variable region selected from the group consisting of

a) a heavy chain variable region comprising a heavy chain CDRl comprising an amino acid sequence as set forth in SEQ ID NO: 33, a heavy chain CDR2 comprising an amino acid sequence as set forth in SEQ ID NO: 34, a heavy chain CDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 35, and a light chain variable region comprising a light

522 chain CDRl comprising an amino acid sequence as set forth in SEQ ID NO: 37, a light chain CDR2 comprising an amino acid sequence as set forth in SEQ ID NO: 38, and a light chain CDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 39;

b) a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:

147, and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 144;

c) a heavy chain variable region comprising a heavy chain CDRl comprising an amino acid sequence as set forth in SEQ ID NO: 10, a heavy chain CDR2 comprising an amino acid sequence as set forth in SEQ ID NO: 140, a heavy chain CDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 12, and a light chain variable region comprising a light chain CDRl comprising an amino acid sequence as set forth in SEQ ID NO: 136, a light chain CDR2 comprising an amino acid sequence as set forth in SEQ ID NO: 7, and a light chain CDR3 comprising an amino acid sequence as set forth in SEQ ID NO: 15; and

d) a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:

139, and a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO: 135.

523