Neutralizing prolactin receptor antibodies and their therapeutic use

1. Antibody 005-C04, 005-C04-10-3, 005-C04-11-5, 005-C04-18-10-2, 005-C04-18-10-4, 005-C04-19-2, 005-C04-2-2, 005-C04-2-7, 005-C04-20-12-7, 005-C04-20-2, 005-C04-21-1, 005-C04-21-2, 005-C04-25-6, 005-C04-29-0, 005-C04-29-17-0, 005-C04-29-17-2, 005-C04-29-17-3, 005-C04-29-17-7, 005-C04-35-3, 005-C04-36-0, 005-C04-37-2, 005-C04-37-7, 005-C04-4-3-7, 005-C04-40-4, 005-C04-41-2, 005-C04-42-1, 005-C04-44-25-1, 005-C04-45-1, 005-C04-46-0, 005-C04-46-1, 005-C04-47-3, 005-C04-48-1, 005-C04-5-5, 005-C04-50-28-3, 005-C04-50-28-7, 005-C04-51-29-0, 005-C04-52-29-0, 005-C04-52-29-7, 005-C04-53-31-7, 005-C04-55-32-0, 005-C04-58-33-1, 005-C04-8-2, 005-C04-8-6, 005-C04-9-2, 005-C04-L2-1-11-0, 005-C04-L2-1-11-3, 005-C04-L2-1-12-2, 005-C04-L2-1-12-4, 005-C04-L2-1-16-4, 005-C04-L2-1-16-5, 005-C04-L2-1-2-3, 005-C04-L2-1-20-0, 005-C04-L2-1-20-1, 005-C04-L2-1-21-7, 005-C04-L2-1-23-7, 005-C04-L2-1-25-0, 005-C04-L2-1-25-4, 005-C04-L2-1-25-5, 005-C04-L2-1-25-7, 005-C04-L2-1-28-7, 005-C04-L2-1-3-2, 005-C04-L2-1-31-4, 005-C04-L2-1-31-7, 005-C04-L2-1-32-4, 005-C04-L2-1-33-7, 005-C04-L2-1-36-6, 005-C04-L2-1-38-3, 005-C04-L2-1-4-5, 005-C04-L2-1-40-2, 005-C04-L2-1-40-7, 005-C04-L2-1-42-0, 005-C04-L2-1-47-0, or 005-C04-L2-1-48-3 or antigen-binding fragments thereof.

2. Antibody or antigen-binding fragments according to claim 1 whereby the antibodies antagonize prolactin receptor-mediate signaling in human and mouse.

3. Antibody or antigen-binding fragment wherein

a. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12 and 17 and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, and 33, or

b. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 104, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

c. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 105, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or

d. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 139, 33; or

e. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or

f. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 106, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 138, 33; or

g. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 106, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

h. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 108, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 137, 28, 33; or

i. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 138, 33; or

j. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 114, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or

k. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 104, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

l. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 111, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or

m. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 116, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

n. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 118, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 138, 33; or

o. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 143; or

p. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 145; or

q. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 144; or

r. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 146; or

s. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 110, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

t. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 110, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or

u. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 127, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or

v. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 127, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or

w. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or

x. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 117, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

y. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or

z. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 115, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 138, 33; or

aa. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

bb. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or

cc. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 116, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

dd. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 107, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or

ee. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 108, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or

ff. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or

gg. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 133, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 138, 33; or

hh. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 123, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

ii. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 120, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

jj. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 125, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

kk. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 134, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

ll. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

mm. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 128, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

nn. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 122, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

oo. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 124, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or

pp. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 106, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or

qq. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 118, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 135, 28, 33; or

rr. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 120, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 142, 33; or

ss. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 117, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 140, 33; or

tt. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 130, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 139, 33; or

uu. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 111, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 140, 33; or

vv. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 114, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or

ww. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 116, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or

xx. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 140, 33; or

yy. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 112, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or

zz. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 116, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 140, 33; or

aaa. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 120, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or

bbb. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 116, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 138, 33; or

ccc. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 109, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or

ddd. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 120, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or

eee. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 105, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 138, 33; or

fff. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 132, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 138, 33; or

ggg. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 120, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or

hhh. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 129, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 140, 33; or

iii. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 117, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 140, 33; or

jjj. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 129, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 142, 33; or

kkk. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 104, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 142, 33; or

lll. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 107, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 142, 33; or

mmm. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 113, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 140, 33; or

nnn. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 131, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 142, 33; or

ooo. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 115, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or

ppp. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or

qqq. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 109, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 138, 33; or

rrr. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 121, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 142, 33; or

sss. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 126, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 142, 33; or

ttt. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 105, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or

uuu. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 108, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 138, 33.

4. Antibody or antigen-binding fragment comprising

a. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 39, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 45,

b. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 187, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 259,

c. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 188, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 260,

d. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 189, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 261,

e. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 190, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 262,

f. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 191, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 263,

g. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 192, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 264,

h. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 193, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 265,

i. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 194, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 266,

j. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 195, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 267,

k. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 196, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 268,

l. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 197, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 269,

m. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 198, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 270,

n. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 199, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 271,

o. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 200, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 272,

p. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 201, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 273,

q. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 202, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 274,

r. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 203, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 275,

s. a variable heavy chain domain corresponding an amino acid sequence according to SEQ ID NO: 204, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 276,

t. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 205, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 277,

u. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 206, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 278,

v. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 207, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 279,

w. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 208, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 280,

x. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 209, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 281,

y. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 210, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 282,

z. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 211, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 283,

aa. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 212, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 284,

bb. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 213, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 285,

cc. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 214, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 286,

dd. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 215, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 287,

ee. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 216, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 288,

ff. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 217, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 289,

gg. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 218, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 290,

hh. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 219, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 291,

ii. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 220, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 292,

jj. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 221, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 293,

kk. a variable heavy chain domain corresponding an amino acid sequence according to SEQ ID NO: 222, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 294,

ll. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 223, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 295,

mm. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 224, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 296,

nn. a variable heavy chain domain corresponding an amino acid sequence according to SEQ ID NO: 225, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 297,

oo. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 226, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 298,

pp. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 227, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 299,

qq. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 228, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 300,

rr. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 229, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 301,

ss. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 230, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 302,

tt. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 231, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 303,

uu. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 232, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 304,

vv. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 233, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 305,

ww. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 234, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 306,

xx. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 235, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 307,

yy. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 236, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 308,

zz. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 237, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 309,

aaa. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 238, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 310,

bbb. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 239, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 311,

ccc. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 240, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 312,

ddd. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 241, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 313,

eee. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 242, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 314,

fff. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 243, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 315,

ggg. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 244, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 316,

hhh. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 245, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 317,

iii. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 246, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 318,

jjj. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 247, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 319,

kkk. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 248, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 320,

lll. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 249, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 321

mmm. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 250, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 322,

nnn. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 251, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 323,

ooo. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 252, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 324,

ppp. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 253, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 325,

qqq. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 254, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 326,

rrr. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 255, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 327,

sss. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 256, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 328,

ttt. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 257, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 329,

uuu. a variable heavy chain domain corresponding to an amino acid sequence according to SEQ ID NO: 258, and a variable light chain domain with an amino acid sequence according to SEQ ID NO: 330.

5. Antibody and antigen-binding fragment according to claim 1 , whereby the antibody consists of an antigen-binding region that binds specifically to or has a high affinity of for one or more regions of PRLR, whose amino acid sequence is depicted by SEQ ID NO: 70 and human polymorphic variants of SEQ ID NO: 70, amino acid position 1 to 210, whereby the affinity is at least 30 nM, more preferred with an affinity of less than about 10 nM, or even more preferred with an affinity of less than 1 nM.

6. Antibody of claim 1 wherein the heavy constant is a modified or unmodified IgG1, IgG2, IgG3 or IgG4.

7. An isolated nucleic acid sequence encoding an antibody or antigen-binding fragment according to claim 1 .

8. An isolated nucleic acid sequence according to claim 7 , whereby the nucleic acid sequences are according to table 5.

9. Expression vector comprising a nucleic acid sequence of claim 7 .

10. Host cell comprising the vector of claim 9 .

11. A method of producing an antibody or antigen-binding fragment, comprising culturing the host cell of claim 10 under suitable conditions and recovering said antibody.

12. A method for treating endometriosis, adenomyosis (endometriosis interna), hot flashes, benign breast disease, mastalgia, benign prostate hyperplasia, hyper- and normoprolactinemic hair loss comprising the step of administering to a patient in need thereof an antibody according to claim 1 .

13. A method of contraception or for preventing pregnancy comprising the step of administering to a patient in need thereof an antibody according to claim 1 .

14. A method for inhibition of lactation comprising the step of administering to a patient in need thereof an antibody according to claim 1 .

15. Antibody 005-C04-10-3, 005-C04-11-5, 005-C04-18-10-2, 005-C04-18-10-4, 005-C04-19-2, 005-C04-2-2, 005-C04-2-7, 005-C04-20-12-7, 005-C04-20-2, 005-C04-21-1, 005-C04-21-2, 005-C04-25-6, 005-C04-29-0, 005-C04-29-17-0, 005-C04-29-17-2, 005-C04-29-17-3, 005-C04-29-17-7, 005-C04-35-3, 005-C 04-36-0, 005-C04-37-2, 005-C04-37-7, 005-C04-4-3-7, 005-C04-40-4, 005-C04-41-2, 005-C04-42-1, 005-C04-44-25-1, 005-C04-45-1, 005-C04-46-0, 005-C04-46-1, 005-C04-47-3, 005-C04-48-1, 005-C04-5-5, 005-C04-50-28-3, 005-C04-50-28-7, 005-C04-51-29-0, 005-C04-52-29-0, 005-C04-52-29-7, 005-C04-53-31-7, 005-C04-55-32-0, 005-C04-58-33-1, 005-C04-8-2, 005-C04-8-6, 005-C04-9-2, 005-C04-L2-1-11-0, 005-C04-L2-1-11-3, 005-C04-L2-1-12-2, 005-C04-L2-1-12-4, 005-C04-L2-1-16-4, 005-C04-L2-1-16-5, 005-C04-L2-1-2-3, 005-C04-L2-1-20-0, 005-C04-L2-1-20-1, 005-C04-L2-1-21-7, 005-C04-L2-1-23-7, 005-C04-L2-1-25-0, 005-C04-L2-1-25-4, 005-C04-L2-1-25-5, 005-C04-L2-1-25-7, 005-C04-L2-1-28-7, 005-C04-L2-1-3-2, 005-C04-L2-1-31-4, 005-C04-L2-1-31-7, 005-C04-L2-1-32-4, 005-C04-L2-1-33-7, 005-C04-L2-1-36-6, 005-C04-L2-1-38-3, 005-C04-L2-1-4-5, 005-C04-L2-1-40-2, 005-C04-L2-1-40-7, 005-C04-L2-1-42-0, 005-C04-L2-1-47-0, or 005-C04-L2-1-48-3, or antigen-binding fragments thereof which antagonize prolactin receptor-mediated signalling.

16. Antibody 005-C04 or an antigen-binding fragment thereof.