Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Reexamination Certificate
1998-04-07
2004-03-30
Eyler, Yvonne (Department: 1646)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
C530S388100, C424S143100, C435S070210
Reexamination Certificate
active
06713609
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the field of anti-type I interferon receptor antibodies, and more particularly to anti-type I interferon receptor antibodies that neutralize the anti-viral cytopathic effects of various type I interferons.
BACKGROUND OF THE INVENTION
The type 1 interferons (IFNS) are cytokines that have pleiotropic effects on a wide variety of cell types. IFNs are best known for their anti-viral activity, but they also have anti-bacterial, anti-protozoal, immunomodulatory, and cell-growth regulatory functions. The type 1 interferons include interferon-&agr; (IFN-&agr;) and interferon-&bgr; (IFN-&bgr;). Human IFN-&agr; (hIFN-&agr;) is a heterogeneous family with at least 23 polypeptides while there is only one IFN-&bgr; polypeptide (
J. Interferon Res
., 13: 443-444 (1993)). The hIFN-&agr; subtypes show more than 70% amino acid sequence homology, and there is approximately 25% amino acid identity with hIFN-&bgr;. The hIFNs-&agr; and hIFN-&bgr; share a common receptor.
Three components of the hIFN-&agr; receptor complex have recently been cloned. The cDNA for the first hIFN-&agr; receptor (hIFNAR1) encodes a 63 kD receptor protein (reported in Uze et al.,
Cell
, 60: 225-234 (1990)). This receptor undergoes extensive glycosylation, which causes it to migrate in gel electrophoresis as a much larger 135 kD protein. The second interferon receptor, hIFNAR2 (hIFN-&agr;&bgr;R long), is a 115 kD protein which mediates a functional signaling complex when associated with hIFNAR1 (reported in Domanski et al.,
J. Biol. Chem
., 270: 21606-21611 (1995)). The third hIFN-&agr; receptor, an IFN-&agr;/&bgr; receptor (hIFN-&agr;&bgr;R short), is a 55 kD protein that can bind to type 1 hIFNs but cannot form a functional complex when associated with hIFNAR1 (reported in Novick et al.,
Cell
, 77: 391-400 (1994)). This IFN-&agr;/&bgr; receptor appears to be an alternatively spliced variant of hIFNAR2.
The unprocessed hIFNAR1 expression product is composed of 557 amino acids including an extracellular domain (ECD) of 409 residues, a transmembrane domain of 21 residues, and an intracellular domain of 100 residues as shown in
FIG. 5
on page 229 of Uze et al., supra. The ECD of IFNAR1 is composed of two domains, domain 1 and domain 2, which are separated by a three-proline motif. There is 19% sequence identity and 50% sequence homology between domains 1 and 2 (Uze et al., supra). Each domain (D200) is composed of approximately 200 residues and can be further subdivided into two homologous subdomains (SD100) of approximately 100 amino acids.
Cytokine receptors have been categorized into two classes based on the distribution of cysteine residues. The class 1 cytokine receptor family includes receptors for human growth hormone (hGHR), erythropoietin, IL-3 and IL-4, while the class 2 cytokine receptor family includes the IFN&ggr; receptor, tissue factor, CRF2-4 and IL-10 receptors. Sequence analysis of the hIFN-&agr; receptors shows that they are related to the class 2 cytokine receptor family.
Through the use of IFNAR1 gene knockout mice, IFNAR1 has been shown to be essential for the response to all type 1 IFNs (Muller et al.,
Science
, 264: 1918-1921 (1994); Cleary et al.,
J. Biol. Chem
., 269: 18747-18749 (1994)) and for the mediation of species-specific IFN signal transduction (Constantinescu et al.,
Proc. Natl. Acad. Sci. USA
, 91: 9602-9606 (1994)).
Benoit et al.,
J. Immunol
., 150: 707-716 (1993) reported an anti-IFNAR1 mAb, 64G12, that was found to inhibit the binding of IFN-&agr;2 (IFN-&agr;A) and IFN-&agr;8 (IFN-&agr;B) to Daudi cells and to inhibit the antiviral activity of IFN-&agr;2, IFN-&bgr; and IFN-&ohgr; (IFN-&agr;
II
1) on Daudi cells. Benoit et al. also reported that 64G12 recognizes an epitope present in domain 1 of IFNAR1. Eid and Tovey,
J. Interferon Cytokine Res
., 15: 205-211 (1995) reported that 64G12 cannot immunoprecipitate cross-linked IFN-&agr;2-receptor complexes from Daudi cells.
SUMMARY OF THE INVENTION
In one aspect, the invention provides an anti-IFNAR1 monoclonal antibody that inhibits the anti-viral activity of a first type I interferon and does not inhibit the anti-viral activity of a second type I interferon.
In another aspect, the invention provides an anti-IFNAR1 monoclonal antibody that inhibits anti-viral activity of a first type I interferon and does not inhibit the anti-viral activity of IFN-&agr;2.
In still another aspect, the invention provides an anti-IFNAR1 monoclonal antibody that inhibits anti-viral activity of a first type I interferon and does not inhibit the anti-viral activity of IFN-&agr;8.
In yet another aspect, the invention provides an anti-IFNAR1 monoclonal antibody that inhibits anti-viral activity of a first type I interferon and does not inhibit the anti-viral activity of IFN-&agr;
II
1.
In a further aspect, the invention provides an anti-IFNAR1 monoclonal antibody that inhibits anti-viral activity of a first type I interferon and does not inhibit the anti-viral activity of IFN-&bgr;.
In an additional aspect, the invention provides an anti-IFNAR1 monoclonal antibody that inhibits the anti-viral activity of a first type I interferon and does not inhibit the anti-viral activity of a second type I interferon selected from the group consisting of IFN-&agr;2, IFN-&agr;8, IFN-&agr;
II
1, and IFN-&bgr;.
The invention also encompasses an anti-IFNAR1 monoclonal antibody that binds to one or more amino acids in situ in the sequence of amino acids 244-249 of IFNAR1, and binds to one or more amino acids in situ in the sequence of amino acids 291-298 of IFNAR1.
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patent: 0 563 487 (1993-10-01), None
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patent: 97/41229 (1997-11-01), None
Abramovich et al., “Differential Tyrosine Phosphorylation of the IFNAR Chain of the Type I Interferon Receptor and of an Associated Surface Protein in Response to IFN-&agr; and IFB &bgr;,” EMBO Journal, 13(24):5871-5877 (1994).
Abramovich et al., “Human IFN-&agr; Receptor Detected by Two Monoclonal Antibodies,” J. Interferon Research, 12(supp. 1):S217 (Sep. 9-Oct. 2, 1992 Annual Mtg., international Society for Interferon Res.) (1992).
Capon, et al., “Two Distinct Families of Human and Bovine Interferon -&agr; Genes are Coordinately Expressed and Encode Functional Polypeptides,” Molecular & Cellular Biology, 5:768-779 (1985).
Chuntharapai, et al., “Structure-Function Studies of Human Interferon -&agr; Receptor II Using Mabs,” FASEB Journal, (Abst. #1877), 10(6):A1325, (Apr. 30, 1996).
Colamonici, et al., “Study of the Structure of the IFN-&agr;2 Receptor by Anti-IFN&agr;2 Receptor Antibodies and Affinity Cross-Linking,” j. Interferon Res., (Abst. 118-6, Annual Int. Society fo Interferon Res. Mtg., Nov. 14-18, 1990). 10(Suppl. 1):S158.
Colamonici, et al., “Identification of a Novel Subunit of the Type I Interferon Receptor Localized to Human Chromosome 21,” Journal of Biological Chemistry, 268(15):10895-10899 (1993).
Colamonici , et al., “Characterization of three Monoclonal Antibodies that Recognized the Interferon &agr;2 Receptor,” Proc. Natl. Acad. Sci., 87:7230-7234 (1990).
Colamonici et al., “Multichain Structure of the IFN -&agr; Receptor on Hematopietic Cells,” J. Immunol., 148(7):2126-2132 (1992).
Goeddel et al., “The Structure of Eight Distinct Cloned Human Leukocyte Interferon cDNAs,” Nature, 290:20-26 (1981).
Hauptmann et al., “A Novel Class of Human Type I Interferons,” Nucleic Acids Research, 13(13):4739-4749 (1985).
Ling et al., “Human Type I Interferon Receptor, IFNAR, is a Heavily Glycosylated 120-130 kD Membrane Protein,” J. Interferon & Cytokine Res., 15:56-61 (1995).
Lu et al., “Structure-Function Studies of IFN-&agr;R Using Mabs Binding to Different Epitopes,” 9th International Congress of Immunology, (Jul. 23-29, 1995) Abst. 713:121 (1996).
Novick et al., “Antibodies to IFN-&agr; Receptor,” J. Interferon Research, (Nov. 3-8, 1991 Annual Mtg., International Society for Interferon Research) 11 (S
Chuntharapai Anan
Kim Kyung Jin
Love Richard B.
Lu Ji
Brannock Micheal T
Eyler Yvonne
Genentech Inc.
Merchant & Gould P.C.
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