Patent EP0451216B1 successfully refreshed from Google Patents.
EP0451216B1
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Humanized immunoglobulins and their production and use
Assignee: PDL Biopharma Inc
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Filing: 1989-12-28
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Granted: 1996-01-24
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Expires: 2009-12-28
Abstract
Abstract Compsn. comprises a pure human-like immunoglobulin (Ig) which (a) reacts specifically with p55 Tac protein and/or (b) inhibits binding of human interleukin-2 (IL-2) to its receptor. Also new are (1) human-like Ig having 2 pairs of light/heavy chains and able to react specifically with an epitope of a human IL-2 receptor with affinity at least 10 power 8 per mole, the chains including complementarily determg. regions (CDR's) and human-like framework regions (FR's), the CDR's being from different Ig molecules than FR's; (2) humanised Ig (hIg) which can bind to IL-2 receptors and contain at least one CDR from anti-Tac antibody in a human-like FR contg. at least one amino acid from the anti-Tac antibody; (3) nucleic acid encoding for human-like FR and at least one murine CDR, and (4) cells transfected with nucleic acid.
Inventors
- 👤 Cary L. Queen
- 👤 Harold Edwin Selick
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-09 14:12
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/08; C07K16/081; C07K16/085; C07K16/087; A; A61; A61P; A61P19/00; A61P19/02; A61P21/00; A61P21/04; A61P25/00; A61P29/00; A61P3/00; A61P3/08; A61P3/10; A61P37/00; A61P37/02; A61P37/06; C07K16/088; C07K16/18; C07K16/24; C07K16/249; C07K16/28; C07K16/2803; C07K16/2866; C07K16/2896; C07K16/46; C07K16/461; C07K16/464; C07K16/465; A61K; A61K38/00; C07K2317/00; C07K2317/20; C07K2317/24; C07K2317/70; C07K2317/73; C07K2317/732; C07K2319/00; C07K2319/01; C07K2319/02; C07K2319/30
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
122 words
The use of at least one amino acid substitution outside of complementarity determining regions (CDR's) as defined by Kabat et al ("'Sequences of Proteins of Immunological Interest", Kabat, E., et al., US Department of Health and Human Services, (1983)) together with Chothia et al (Chothia and Lesk, J. Mol. Biol., 196 :901-917 (1987)) in the production of a humanized immunoglobulin, wherein said amino acid substitution is from the non-CDR variable region of a non-human donor immunoglobulin, and in which humanized immunoglobulin the variable region amino acid sequence other than the CDR's comprises at least 70 amino acid residues identical to an acceptor human immunoglobulin variable region amino acid sequence, and the CDR's are from the variable region of said non-human donor immunoglobulin.
Claim 2
Dependent Claim
41 words
A use according to claim 1, wherein said humanized immunoglobulin is specifically reactive with p55 Tac protein, is capable of inhibiting binding of human interleukin-2 (IL-2) to a human IL-2 receptor, or is capable of binding to a human IL-2 receptor.
Claim 3
Dependent Claim
26 words
A use according to claim 2, wherein said humanized immunoglobulin exhibits a binding affinity to a human IL- 2 receptor of about 10⁸ M⁻¹ or stronger.
Claim 4
Dependent Claim
35 words
A use according to claim 2 or claim 3, wherein the mature light and heavy variable region protein sequences of said humanized immunoglobulin are homologous to the mature protein sequences in Figures 3 and 4.
Claim 5
Dependent Claim
20 words
A use according to any one of claims 1 to 4, wherein said humanized immunoglobulin is an IgG₁ immunoglobulin isotype.
Claim 6
Dependent Claim
19 words
A use according to any one of claims 1 to 5, wherein said substitution is immediately adjacent a CDR.
Claim 7
Independent Claim
139 words
A method of producing a humanized immunoglobulin chain having a framework region from a human acceptor immunoglobulin and complementarity determining regions (CDR's) from a donor immunoglobulin capable of binding to an antigen, said method comprising substituting at least one non-CDR framework amino acid of the acceptor immunoglobulin with a corresponding amino acid from the donor immunoglobulin at a position in the immunoglobulins where: (a) the amino acid in the human framework region of the acceptor immunoglobulin is rare for said position and the corresponding amino acid in the donor immunoglobulin is common for said position in human immunoglobulin sequences; or (b) the amino acid is immediately adjacent to one of the CDR's; or (c) the amino acid is predicted to have a side chain atom capable of interacting with the antigen or with the CDR's of the humanized immunoglobulin.
Claim 8
Dependent Claim
33 words
A method according to claim 7, wherein there are at least three of said non-CDR framework amino acids substituted by amino acids from the donor immunoglobulin chosen by criteria (a), (b) or (c).
Claim 9
Dependent Claim
24 words
A method according to claim 8, wherein at least one of the amino acids substituted from the donor is immediately adjacent to a CDR.
Claim 10
Independent Claim
37 words
A method according to any one of claims 7 to 9, wherein the mature light and heavy variable region protein sequences of said humanized immunoglobulin are homologous to the mature protein sequences in Figures 3 and 4.
Claim 11
Dependent Claim
17 words
A humanized immunoglobulin chain obtainable by a use according to any one of claims 1 to 6.
Claim 12
Dependent Claim
17 words
A humanized immunoglobulin chain obtainable by a method according to any one of claims 7 to 10.
Claim 13
Dependent Claim
19 words
A humanized immunoglobulin in which the heavy and light chains are chains according to claim 11 or claim 12.
Claim 14
Dependent Claim
39 words
A polynucleotide comprising a first sequence coding for a human-like immunoglobulin non-CDR framework region and a second sequence coding for one or more CDR's, wherein upon expression said polynucleotide encodes an immunoglobulin chain of claim 11 or claim 12.
Claim 15
Dependent Claim
17 words
Polynucleotides according to claim 14 which upon expression encode the chains constituting an immunoglobulin of claim 13.
Claim 16
Dependent Claim
15 words
A cell line transfected with a polynucleotide or polynucleotides of claim 14 or claim 15.
Claim 17
Dependent Claim
36 words
A process for the preparation of a humanized immunoglobulin as defined in claim 13, which process comprises cultivating a cell line as defined in claim 16 and isolating the humanized immunoglobulin from the cell culture medium.
Claim 18
Dependent Claim
19 words
The use of an immunoglobulin of claim 13 or a binding fragment thereof in the manufacture of a medicament.
Claim 19
Dependent Claim
21 words
A use according to claim 18 in which the medicament is suitable for treating T-cell mediated disorders in a human patient.
Claim 20
Dependent Claim
18 words
A pharmaceutical preparation which contains a humanized immunoglobulin according to claim 13 formulated in a pharmaceutically acceptable form.
Claim 21
Dependent Claim
15 words
A pharmaceutical preparation according to claim 20 and for the treatment of T-cell mediated disorders.
References Cited (Backward Citations)
No citation records indexed.
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