IP Library › Patent Application 19574218
Patent Application
App. No. 19/574,218

ANTIGEN BINDING PROTEINS

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Patent No.
US None
App. No.
19/574,218
Abstract

The present disclosure relates to antigen binding proteins. More particularly the present disclosure relates to pregnancy associated plasma protein-A (PAPPA) binding proteins, even more particularly PAPPA binding proteins that inhibit cleavage of insulin like growth factor binding protein-2 (IGFBP-2), insulin like growth factor binding protein-4 (IGFBP-4) and insulin like growth factor binding protein-5 (IGFBP-5). The present disclosure further relates to the use of said binding proteins in medicine.

Claims (43)

1 . A PAPPA binding protein comprising a variable heavy chain (VH) region comprising three heavy chain CDR sequences, CDRH1, CDRH2, and CDRH3, and a variable light chain (VL) region comprising three light chain CDR sequences, CDRL1, CDRL2, and CDRL3, wherein:

a) CDRH1 comprises SEQ ID NO: 47; CDRH2 comprises SEQ ID NO: 48; CDRH3 comprises SEQ ID NO: 49; CDRL1 comprises SEQ ID NO: 53; CDRL2 comprises SEQ ID NO: 54; and CDRL3 comprises SEQ ID NO: 55; or

b) CDRH1 comprises SEQ ID NO: 71; CDRH2 comprises SEQ ID NO: 72; CDRH3 comprises SEQ ID NO: 73; CDRL1 comprises SEQ ID NO: 77; CDRL2 comprises SEQ ID NO: 78; and CDRL3 comprises SEQ ID NO: 79; or

c) CDRH1 comprises SEQ ID NO: 95; CDRH2 comprises SEQ ID NO: 96; CDRH3 comprises SEQ ID NO: 97; CDRL1 comprises SEQ ID NO: 101; CDRL2 comprises SEQ ID NO: 102; and CDRL3 comprises SEQ ID NO: 103; or

d) CDRH1 comprises SEQ ID NO: 107; CDRH2 comprises SEQ ID NO: 108; CDRH3 comprises SEQ ID NO: 109; CDRL1 comprises SEQ ID NO: 113; CDRL2 comprises SEQ ID NO: 114; and CDRL3 comprises SEQ ID NO: 115.

2 . The PAPPA binding protein of claim 1 , wherein said binding protein comprises a VH region that is 100% identical to SEQ ID NO: 45, SEQ ID NO: 69, SEQ ID NO: 93, or SEQ ID NO: 105.

3 . The PAPPA binding protein of claim 1 , wherein said binding protein comprises a VL region that is 100% identical to SEQ ID NO: 51, SEQ ID NO: 75, SEQ ID NO: 99, or SEQ ID NO: 111.

4 . The PAPPA binding protein of claim 1 , wherein said binding protein comprises a) a VH region that is 100% identical to SEQ ID NO: 45 and a VL region that is 100% identical to SEQ ID NO: 51; or b) a VH region that is 100% identical to SEQ ID NO: 69 and a VL region that is 100% identical to SEQ ID NO: 75; or c) a VH region that is 100% identical to SEQ ID NO: 93 and a VL region that is 100% identical to SEQ ID NO: 99; or d) a VH region that is 100% identical to SEQ ID NO: 105 and a VL region that is 100% identical to SEQ ID NO: 111.

5 . The PAPPA binding protein of claim 1 , wherein said binding protein comprises a heavy chain constant region as shown in SEQ ID NO: 17 and a light chain constant region as shown in SEQ ID NO: 19.

6 . The PAPPA binding protein of claim 4 , wherein said binding protein comprises a heavy chain and a light chain, wherein:

a) the amino acid sequence of the heavy chain is shown in SEQ ID NO: 44 and the amino acid sequence of the light chain is shown in SEQ ID NO: 50; or

b) the amino acid sequence of the heavy chain is shown in SEQ ID NO: 68 and the amino acid sequence of the light chain is shown in SEQ ID NO: 74; or

c) the amino acid sequence of the heavy chain is shown in SEQ ID NO: 92 and the amino acid sequence of the light chain is shown in SEQ ID NO: 98; or

d) the amino acid sequence of the heavy chain is shown in SEQ ID NO: 104 and the amino acid sequence of the light chain is shown in SEQ ID NO: 110.

7 . A PAPPA binding protein that binds to an epitope within the central M region of human PAPPA.

8 . The PAPPA binding protein of claim 7 , wherein said binding protein binds to an epitope within the M1/M2 region of human PAPPAs corresponding to amino acids 673-1213 of SEQ ID NO: 1.

9 . The PAPPA binding protein of claim 8 , wherein said epitope comprises one or more amino acids within residues 1067-1079 of SEQ ID NO: 1.

10 . The PAPPA binding protein of claim 1 , wherein said binding protein inhibits cleavage of IGFBP-2, IGFBP-4 and IGFBP-5.

11 . The PAPPA binding protein of claim 1 , wherein said binding protein binds to human PAPPA with an affinity (KD) of less than 1 nM, wherein affinity (KD) is measured using surface plasmon resonance (SPR) at 25° C. or 37° C.

12 . The PAPPA binding protein of claim 1 , wherein said PAPPA binding protein is a human or humanized PAPPA binding protein.

13 . The PAPPA binding protein of claim 1 , wherein said PAPPA binding protein is an antibody or an antigen binding fragment thereof.

14 . The PAPPA binding protein of claim 7 , wherein said binding protein inhibits cleavage of IGFBP-2, IGFBP-4 and IGFBP-5.

15 . The PAPPA binding protein of claim 7 , wherein said binding protein binds to human PAPPA with an affinity (KD) of less than 1 nM, wherein affinity (KD) is measured using surface plasmon resonance (SPR) at 25° C. or 37° C.

16 . The PAPPA binding protein of claim 7 , wherein said PAPPA binding protein is a human or humanized PAPPA binding protein.

17 . The PAPPA binding protein of claim 7 , wherein said PAPPA binding protein is an antibody or an antigen binding fragment thereof.

18 . A nucleic acid sequence that encodes a PAPPA binding protein comprising a variable heavy chain (VH) region comprising three heavy chain CDR sequences, CDRH1, CDRH2, and CDRH3, and a variable light chain (VL) region comprising three light chain CDR sequences, CDRL1, CDRL2, and CDRL3, wherein:

a) CDRH1 comprises SEQ ID NO: 47; CDRH2 comprises SEQ ID NO: 48; CDRH3 comprises SEQ ID NO: 49; CDRL1 comprises SEQ ID NO: 53; CDRL2 comprises SEQ ID NO: 54; and CDRL3 comprises SEQ ID NO: 55; or

b) CDRH1 comprises SEQ ID NO: 71; CDRH2 comprises SEQ ID NO: 72; CDRH3 comprises SEQ ID NO: 73; CDRL1 comprises SEQ ID NO: 77; CDRL2 comprises SEQ ID NO: 78; and CDRL3 comprises SEQ ID NO: 79; or

c) CDRH1 comprises SEQ ID NO: 95; CDRH2 comprises SEQ ID NO: 96; CDRH3 comprises SEQ ID NO: 97; CDRL1 comprises SEQ ID NO: 101; CDRL2 comprises SEQ ID NO: 102; and CDRL3 comprises SEQ ID NO: 103; or

d) CDRH1 comprises SEQ ID NO: 107; CDRH2 comprises SEQ ID NO: 108; CDRH3 comprises SEQ ID NO: 109; CDRL1 comprises SEQ ID NO: 113; CDRL2 comprises SEQ ID NO: 114; and CDRL3 comprises SEQ ID NO: 115.

19 . An expression vector comprising the nucleic acid sequence of claim 18 .

20 . A recombinant host cell comprising the nucleic acid sequence of the expression vector of claim 19 .

21 . A method for the production of a PAPPA binding protein, said method comprising culturing the host cell of claim 20 under conditions suitable for expression, whereby a PAPPA binding protein is produced.

22 . A PAPPA binding protein produced by the method of claim 21 .

23 . A cell line engineered to express the PAPPA binding protein of claim 1 .

24 . A pharmaceutical composition comprising the PAPPA binding protein of claim 1 .

25 . A method for the treatment of a disease in a subject in need thereof comprising administering to said subject a therapeutically effective amount of the PAPPA binding protein as defined in claim 1 or the pharmaceutical composition of claim 24 .

26 . A method for the treatment of a polycystic kidney disease (PKD) in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a PAPPA binding protein comprising a variable heavy chain (VH) region comprising three heavy chain CDR sequences, CDRH1, CDRH2, and CDRH3, and a variable light chain (VL) region comprising three light chain CDR sequences, CDRL1, CDRL2, and CDRL3, wherein:

a) CDRH1 comprises SEQ ID NO: 47; CDRH2 comprises SEQ ID NO: 48; CDRH3 comprises SEQ ID NO: 49; CDRL1 comprises SEQ ID NO: 53; CDRL2 comprises SEQ ID NO: 54; and CDRL3 comprises SEQ ID NO: 55; or

b) CDRH1 comprises SEQ ID NO: 71; CDRH2 comprises SEQ ID NO: 72; CDRH3 comprises SEQ ID NO: 73; CDRL1 comprises SEQ ID NO: 77; CDRL2 comprises SEQ ID NO: 78; and CDRL3 comprises SEQ ID NO: 79; or

c) CDRH1 comprises SEQ ID NO: 95; CDRH2 comprises SEQ ID NO: 96; CDRH3 comprises SEQ ID NO: 97; CDRL1 comprises SEQ ID NO: 101; CDRL2 comprises SEQ ID NO: 102; and CDRL3 comprises SEQ ID NO: 103; or

d) CDRH1 comprises SEQ ID NO: 107; CDRH2 comprises SEQ ID NO: 108; CDRH3 comprises SEQ ID NO: 109; CDRL1 comprises SEQ ID NO: 113; CDRL2 comprises SEQ ID NO: 114; and CDRL3 comprises SEQ ID NO: 115.

27 . The method of claim 26 wherein the PKD is autosomal dominant PKD (ADPKD).