US2010056762A1PendingUtilityA1

Specific binding proteins and uses thereof

Individually held — no corporate assignee on recordPriority: May 11, 2001Filed: Feb 18, 2009Published: Mar 4, 2010

Est. expiryMay 11, 2021(expired)· nominal 20-yr term from priority

A61P 35/00A61P 43/00A61K 51/103C07K 2317/732C07K 2317/24C07K 2317/77A61K 51/1045C07K 16/40C07K 2317/51C07K 2317/515A61K 31/495C07K 2317/734C07K 2317/73A61K 39/39541C07K 2317/34C07K 16/2863C07K 16/4258A61K 2039/505C07K 2317/92C07K 2317/52A61K 39/39558A61K 51/1078C07K 2317/565C07K 16/30A61K 2300/00A61K 47/6871C07K 2317/56C07K 2317/622C07K 2317/54A61K 47/68A61K 39/395G01N 33/575A61K 47/6849

PatentIndex Score

Cited by

References

Claims

Abstract

The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.

Claims

exact text as granted — not AI-modified

1 . An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO:13, wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEQ ID NO:14) of human wild-type EGFR, and wherein said antibody does not comprise a heavy chain variable region sequence having the amino acid sequence set forth in SEQ ID NO:2 and does not comprise a light chain variable region sequence having the amino acid sequence set forth in SEQ ID NO:4.

2 . (canceled)

3 . An isolated antibody according to claim 1 , wherein said antibody comprises a heavy chain and a light chain, said heavy chain having the amino acid sequence set forth in SEQ ID NO:129, and said light chain having the amino acid sequence set forth in SEQ ID NO:134.

4 . An isolated antibody according to claim 1 , wherein said antibody comprises a heavy chain and a light chain, said heavy chain having the amino acid sequence set forth in SEQ ID NO:22, and said light chain having the amino acid sequence set forth in SEQ ID NO:27.

5 . An isolated antibody according to claim 1 , wherein said antibody comprises a heavy chain and a light chain, said heavy chain having the amino acid sequence set forth in SEQ ID NO:32, and said light chain having the amino acid sequence set forth in SEQ ID NO:37.

6 . (canceled)

7 . (canceled)

8 . An isolated antibody according to claim 1 , wherein said antibody comprises a heavy chain and a light chain, wherein the variable region of said heavy chain comprises polypeptide binding domain regions having amino acid sequences highly homologous to the amino acid sequences set forth in SEQ ID NOS:130, 131, and 132.

9 . An isolated antibody according to claim 1 , wherein said antibody comprises a heavy chain and a light chain, wherein the variable region of said light chain comprises polypeptide binding domain regions having amino acid sequences highly homologous to the amino acid sequences set forth in SEQ ID NOS:135, 136, and 137.

10 . (canceled)

11 . (canceled)

12 . (canceled)

13 . (canceled)

14 . An isolated antibody according to claim 1 , wherein said isolated antibody is the form of an antibody F(ab′)2, scfv fragment, diabody, triabody or tetrabody.

15 . An isolated antibody according to claim 1 , further comprising a detectable or functional label.

16 . An isolated antibody according to claim 15 , wherein said detectable or functional label is a covalently attached drug.

17 . An isolated antibody according to claim 15 , wherein said label is a radiolabel.

18 . An isolated antibody according to claim 1 , wherein said isolated antibody is peglyated.

19 . (canceled)

20 . (canceled)

21 . (canceled)

22 . (canceled)

23 . (canceled)

24 . (canceled)

25 . (canceled)

26 . (canceled)

27 . (canceled)

28 . (canceled)

29 . (canceled)

30 . (canceled)

31 . (canceled)

32 . (canceled)

33 . (canceled)

34 . (canceled)

35 . (canceled)

36 . (canceled)

37 . (canceled)

38 . (canceled)

39 . (canceled)

40 . An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody comprises a heavy chain and a light chain, said heavy chain having an amino acid sequence that is substantially homologous to the amino acid sequence set forth in SEQ ID NO: 129, and said light chain having an amino acid sequence that is substantially homologous to the amino acid sequence set forth in SEQ ID NO: 134.

41 . An isolated antibody according to claim 40 , wherein said heavy chain of said antibody comprises the amino acid sequence set forth in SEQ ID NO:129, and wherein said light chain of said antibody comprises the amino acid sequence set forth in SEQ ID NO: 134.

42 . An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody comprises a heavy chain and a light chain, wherein the variable region of said heavy chain comprises polypeptide binding domain regions having amino acid sequences highly homologous to the amino acid sequences set forth in SEQ ID NOS:130, 131, and 132, and wherein the variable region of said light chain comprises polypeptide binding domain regions having amino acid sequences highly homologous to the amino acid sequences set forth in SEQ ID NOS: 135, 136, and 137.

43 . (canceled)

44 . (canceled)

45 . (canceled)

46 . (canceled)

47 . (canceled)

48 . (canceled)

49 . An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO: 13, wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEO ID NO:14) of human wild-type EGFR,
said antibody comprising a light chain and a heavy chain, wherein the variable region of said light chain comprises a first polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula I:

HSSQDIX aa1 SNIG (I),

wherein X aa1 is an amino acid residue having an uncharged polar R group;
a second polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula II:

HGTNLX aa2 D (IL),

wherein X aa2 is an amino acid residue having a charged polar R group;
and a third polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula III:

VQYX aa3 QFPWT (III),

wherein X aa3 is selected from the group consisting of A, G, and an amino acid residue which is conservatively substituted for A or G; and
wherein the variable region of said heavy chain comprises a first polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula IV:

SDX aa4 AWN (IV),

wherein X aa4 is selected from the group consisting of F, Y, and an amino acid residue which is conservatively substituted for F or Y;
a second polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula V, Formula VI, or Formula VII:

YISYSGNTRYX aa5 PSLKS (V),

wherein X aa5 is an amino acid residue having an uncharged polar R group,

YISYSX aa6 NTRYNPSLKS (VI),

wherein X aa6 is selected from the group consisting of G, A, and an amino acid residue which is conservatively substituted for G or A,

YISYSGNTRYNPSLX aa7 S (VII),

and X aa7 is a basic amino acid residue; and
a third polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula VIII:

X aa8 TAGRGFPY (VIII),

wherein X aa8 is selected from the group consisting of V, A, and an amino acid residue which is conservatively substituted for V or A,
and wherein said antibody does not comprise a heavy chain variable region sequence having the amino acid sequence set forth in SEQ ID NO:2 and does not comprise a light chain variable region sequence having the amino acid sequence set forth in SEQ ID NO:4.

50 . An isolated antibody according to claim 49 , wherein X aa1 is N; X aa2 is D; X aa3 is A; X aa4 is F; X aa5 is an amino acid residue having an uncharged polar R group; X aa6 is G; X aa7 is K; and X aa8 is V.

51 . An isolated antibody according to claim 50 , wherein Xaa 5 is N or Q.

52 . An antibody according to claim 49 , wherein X aa1 is N or S.

53 . An antibody according to claim 49 , wherein X aa2 is D or E.

54 . An antibody according to claim 49 , wherein X aa3 is A or G.

55 . An antibody according to claim 49 , wherein X aa4 is F or Y.

56 . An antibody according to claim 49 , wherein X aa5 is N or Q.

57 . An antibody according to claim 49 , wherein X aa6 is G or A, and X aa7 is independently K or R.

58 . An antibody according to claim 49 , wherein X aa8 is V or A.

59 . (canceled)

60 . (canceled)

61 . (canceled)

62 . (canceled)

63 . (canceled)

64 . (canceled)

65 . (canceled)

66 . (canceled)

67 . (canceled)

68 . (canceled)

69 . (canceled)

70 . (canceled)

71 . (canceled)

72 . (canceled)

73 . (canceled)

74 . (canceled)

75 . (canceled)

76 . (canceled)

77 . (canceled)

78 . (canceled)

79 . (canceled)

80 . (canceled)

81 . (canceled)

82 . An isolated antibody capable of binding EGFR on tumors containing amplifications of the EGFR gene, wherein cells of said tumors contain multiple copies of the EGFR gene, and on tumors that express the truncated version of the EGFR receptor de2-7, wherein said antibody does not bind to the de2-7 EGFR junctional peptide consisting of the amino acid sequence of SEQ ID NO:13, wherein said antibody binds to an epitope within the sequence of residues 273-501 of human wild-type EGFR,
said antibody comprising a light chain and a heavy chain, wherein the variable region of said light chain comprises a first polypeptide binding domain region having the amino acid sequence HSSQDINSNIG (SEQ ID NO:18); a second polypeptide binding domain region having the amino acid sequence HGTNLDD (SEQ ID NO:19); and a third polypeptide binding domain region having the amino acid sequence VQYAQFPWT (SEQ ID NO:20), wherein the variable region of said heavy chain comprises a first polypeptide binding domain region having the amino acid sequence SDFAWN (SEQ ID NO:15); a second polypeptide binding domain region having an amino acid sequence corresponding to the amino acid sequence set forth in Formula IX:

YISYSGNTRYX aa9 PSLKS (IX),

wherein X aa9 is an amino acid residue having an uncharged polar R group; and
a third polypeptide binding domain region having the amino acid sequence

VTAGRGFPY.
(SEQ ID NO: 17)

83 . An isolated antibody according to claim 82 , wherein said antibody binds to an epitope within the sequence of residues 287-302 (SEQ ID NO:14) of human wild-type EGFR.

84 . An isolated antibody according to claim 82 , wherein X aa9 is N or Q.

85 . An isolated antibody according to claim 82 , wherein said binding domain regions are carried by a human antibody framework.

86 . An isolated antibody according to claim 85 , wherein said human antibody framework is a human IgG1 antibody framework.

Join the waitlist — get patent alerts

Track US2010056762A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.