US2006039906A1PendingUtilityA1
Humanized antibodies that sequester abeta peptide
Est. expiryFeb 24, 2020(expired)· nominal 20-yr term from priority
Inventors:David HoltzmanRonald DemattosKelly R. BalesSteven M. PaulNaoya TsurushitaMaximiliano Vasquez
A61P 25/28A61P 25/00C07K 2317/24C07K 2317/34C07K 2317/76C07K 2317/567A61K 2039/505C07K 16/18C07K 2317/565A61K 39/39533C07K 2317/92
55
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Claims
Abstract
A method to treat conditions characterized by formation of amyloid plaques both prophylactically and therapeutically is described. The method employs humanized antibodies which sequester soluble Aβ peptide from human biological fluids or which preferably specifically bind an epitope contained within position 13-28 of the amyloid beta peptide Aβ.
Claims
exact text as granted — not AI-modified1 - 45 . (canceled)
46 . An immunologically effective fragment of a humanized antibody, wherein the humanized antibody comprises:
a. a light chain comprising three light chain complementarity determining regions (CDRs) having the following amino acid sequences: light chain CDR1: (SEQ ID NO:1) 1 5 10 15 Arg Ser Ser Gln Ser Leu Ile Tyr Ser Asp Gly Asn Ala Tyr Leu His; or (SEQ ID NO:15) 1 5 10 15 Arg Ser Ser Gln Ser Leu Val Tyr Ser Asp Gly Asn Ala Tyr Leu His light chain CDR2: 1 5 Lys Val Ser Asn Arg Phe Ser (SEQ ID NO:2) and, light chain CDR3: 1 5 Ser Gln Ser Thr His Val Pro Trp Thr (SEQ ID NO:3) and a light chain framework sequence from a humanized immunoglobulin light chain; and b. a heavy chain comprising three heavy chain CDRs having the following amino acid sequences: heavy chain CDR1: 1 5 Arg Tyr Ser Met Ser (SEQ ID NO:4) heavy chain CDR2: (SEQ ID NO:5) 1 5 10 15 Gln Ile Asn Ser Val Gly Asn Ser Thr Tyr Tyr Pro Asp Thr Val Lys Gly; or (SEQ ID NO:16) 1 5 10 15 Gln Ile Asn Ser Val Gly Asn Ser Thr Tyr Tyr Pro Asp Ser Val Lys Gly and, heavy chain CDR3: 1 Gly Asp Tyr (SEQ ID NO:6) and a heavy chain framework sequence from a humanized immunoglobulin heavy chain.
47 . The fragment of claim 46 , wherein light chain CDR1 is:
(SEQ ID NO:1)
1 5 10 15
Arg Ser Ser Gln Ser Leu Ile Tyr Ser Asp Gly Asn Ala Tyr Leu His,
and
heavy chain CDR2 is:
(SEQ ID NO:5)
1 5 10 15
Gln Ile Asn Ser Val Gly Asn Ser Thr Tyr Tyr Pro Asp Thr Val Lys Gly
48 . The fragment of claim 46 , wherein the humanized antibody comprises a humanized light chain variable region comprising the following sequence:
(SEQ ID NO:7)
1 5 10 15
Asp Xaa Val Met Thr Gln Xaa Pro Leu Ser Leu Pro Val Xaa Xaa
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Xaa
35 40 45
Tyr Ser Asp Gly Asn Ala Tyr Leu His Trp Phe Leu Gln Lys Pro
50 55 60
Gly Gln Ser Pro Xaa Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe
65 70 75
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
80 85 90
Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Xaa Gly Val
95 100 105
Tyr Tyr Cys Ser Gln Ser Thr His Val Pro Trp Thr Phe Gly Xaa
110
Gly Thr Xaa Xaa Glu Ile Lys Arg
wherein:
Xaa at position 2 is Val or lie;
Xaa at position 7 is Ser or Thr;
Xaa at position 14 is Thr or Ser;
Xaa at position 15 is Leu or Pro;
Xaa at position 30 is lie or Val;
Xaa at position 50 is Arg, Gln, or Lys;
Xaa at position 88 is Val or Leu;
Xaa at position 105 is Gln or Gly;
Xaa at position 108 is Lys or Arg; and
Xaa at position 109 is Val or Leu;
and a heavy chain variable region comprising the following sequence:
(SEQ ID NO:8)
1 5 10 15
Xaa Val Gln Leu Val Glu Xaa Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
35 40 45
Arg Tyr Ser Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Xaa Leu Val Ala Gln Ile Asn Ser Val Gly Asn Ser Thr Tyr Tyr
65 70 75
Pro Asp Xaa Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Xaa
80 85 90
Xaa Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Xaa Asp
95 100 105
Thr Ala Val Tyr Tyr Cys Ala Ser Gly Asp Tyr Trp Gly Gln Gly
110
Thr Xaa Val Thr Val Ser Ser
wherein:
Xaa at position 1 is Glu or Gln;
Xaa at position 7 is Ser or Leu;
Xaa at position 46 is Glu, Val, Asp, or Ser;
Xaa at position 63 is Thr or Ser;
Xaa at position 75 is Ala, Ser, Val, or Thr;
Xaa at position 76 is Lys or Arg;
Xaa at position 89 is Glu or Asp; and
Xaa at position 107 is Leu or Thr.
49 . The fragment of claim 46 , the humanized antibody having a light chain variable region of the sequence given by SEQ ID NO:9 and a heavy chain variable region given by SEQ ID NO:10.
50 . The fragment of claim 49 , the humanized antibody having a light chain of the sequence given by SEQ ID NO:11 and a heavy chain of the sequence given by SEQ ID NO:12.
51 . The fragment of claim 46 , wherein the fragment is a F ab , F ab′ , or F (ab′) 2 fragment.
52 . The fragment of claim 47 , wherein the fragment is a F ab , F ab′ , or F (ab′) 2 fragment.
53 . The fragment of claim 48 , wherein the fragment is a F ab , F ab′ , or F (ab′) 2 fragment.
54 . The fragment of claim 49 , wherein the fragment is a F ab , F ab′ , or F (ab′) 2 fragment.
55 . The fragment of claim 50 , wherein the fragment is a F ab , F ab′ , or F (ab′) 2 fragment.
56 . The fragment of claim 46 , wherein the humanized antibody is an IgG 1 immunoglobulin isotype.
57 . The fragment of claim 47 , wherein the humanized antibody is an IgG 1 immunoglobulin isotype.
58 . The fragment of claim 48 , wherein the humanized antibody is an IgG 1 immunoglobulin isotype.
59 . The fragment of claim 49 , wherein the humanized antibody is an IgG 1 immunoglobulin isotype.
60 . The fragment of claim 50 , wherein the humanized antibody is an IgG 1 immunoglobulin isotype.
61 . The fragment of claim 46 , wherein the fragment is produced in a host cell selected from the group consisting of a myeloma cell, a chinese hamster ovary cell, a syrian hamster ovary cell, and a human embryonic kidney cell.
62 . A pharmaceutical composition that comprises the fragment of claim 46 and a pharmaceutically acceptable excipient.
63 . A pharmaceutical composition that comprises the fragment of claim 47 and a pharmaceutically acceptable excipient.
64 . A pharmaceutical composition that comprises the fragment of claim 48 and a pharmaceutically acceptable excipient.
65 . A pharmaceutical composition that comprises the fragment of claim 50 and a pharmaceutically acceptable excipient.Cited by (0)
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