Claims for Patent: 5,728,677

Summary for Patent: 5,728,677

Title:	Methods of inhibiting T-cell dependent proliferation of peripheral blood lymphocytes using the CD2-binding domain of lymphocyte function associated antigen 3
Abstract:	Polypeptides and proteins comprising the CD2-binding domain of LFA-3 are disclosed. DNA sequences that code on expression for those polypeptides and proteins, methods of producing and using those polypeptides and proteins, and therapeutic and diagnostic compositions are also disclosed. Deletion mutants unable to bind CD2 and methods for their use are also disclosed. In addition, fusion proteins which comprise the CD2-binding domain of LFA-3 and a portion of a protein other than LFA-3, DNA sequences encoding those fusion proteins, methods for producing those fusion proteins, and uses of those fusion proteins are disclosed.
Inventor(s):	Wallner; Barbara P. (Cambridge, MA), Miller; Glenn T. (Haverhill, MA), Rosa; Margaret D. (Winchester, MA)
Assignee:	Biogen, Inc. (Cambridge, MA)
Application Number:	08/459,512
Patent Claims:	1. A method for inhibiting T Cell-dependent proliferation of peripheral blood lymphocytes comprising the step of administering to a mammal a polypeptide having the amino acid sequence: X.sub.1 -X.sub.2 -(SEQ ID NO:1) Asn Arg Val Tyr Leu Asp Thr Val Ser Gly-Y, wherein: X.sub.1 if present, is hydrogen or methionyl; X.sub.2, if present, is a polypeptide having the following amino acid sequence or a portion thereof consisting of the carboxy-terminal 1 to 77 amino acids of the sequence (SEQ ID NO:5): Val Ala Gly Ser Asp Ala Gly Arg Ala Leu Gly Val Leu Ser Val Val Cys Leu Leu His Cys Phe Gly Phe Ile Ser Cys Phe Ser Gln Gln Ile Tyr Gly Val Val Tyr Gly Asn Val Thr Phe His Val Pro Ser Asn Val Pro Leu Lys Glu Val Leu Trp Lys Lys Gln Lys Asp Lys Val Ala Glu Leu Glu Asn Ser Glu Phe Arg Ala Phe Ser Ser Phe Lys; Y is hydroxyl or a polypeptide of the following amino acid sequence or a portion thereof consisting of the amino terminal 1 to 32 amino acids of the sequence (SEQ ID NO:33): Ser Leu Thr Ile Tyr Asn Leu Thr Ser Ser Asp Glu Asp Glu Tyr Glu Met Glu Ser Pro Asn Ile Thr Asp Thr Met Lys Phe Phe Leu Tyr Val; said polypeptide being capable of binding to CD2. 2. The method of claim 1 wherein: X.sub.2, if present, is a polypeptide having the following amino acid sequence or a portion thereof consisting of the carboxy terminal 1 to 50 amino acids of the sequence (SEQ ID NO:2): Phe Ser Gln Gln Ile Tyr Gly Val Val Tyr Gly Asn Val Thr Phe His Val Pro Ser Asn Val Pro Leu Lys Glu Val Leu Trp Lys Lys Gln Lys Asp Lys Val Ala Glu Leu Glu Asn Ser Glu Phe Arg Ala Phe Ser Ser Phe Lys; Y is hydroxyl or a polypeptide of the following amino acid sequence or a portion thereof consisting of the amino-terminal 1 to 10 amino acids of the sequence (SEQ ID NO:3): Ser Leu Thr Ile Tyr Asn Leu Thr Ser Ser; said polypeptide being capable of binding to CD2. 3. The method of claim 1 wherein the polypeptide is selected from the group consisting of polypeptides having the amino acid sequences: amino acids 29-120 of SEQ ID NO:10, amino acids 29-108 of SEQ ID NO:10, amino acids 48-108 of SEQ ID NO:10, and SEQ ID NO:7. 4. The method of claim 1 wherein the polypeptide has the amino acid sequence (SEQ ID NO:7): Lys Asn Arg Val Tyr Leu Asp Thr Val Ser Gly Ser Leu Thr Ile Tyr. 5. A method for inhibiting T cell-dependent proliferation of peripheral blood lymphocytes comprising the step of administering to a mammal a fusion protein having an amino terminal region consisting of the amino acid sequence of a polypeptide selected from the group consisting of: (a) a polypeptide having the amino acid sequence: X.sub.1 -X.sub.2 -(SEQ ID NO:1) Asn Arg Val Tyr Leu Asp Thr Val Ser Gly-Y, wherein: X.sub.1 if present, is hydrogen or methionyl; X.sub.2, if present, is a polypeptide having the following amino acid sequence or a portion thereof consisting of the carboxy-terminal 1 to 77 amino acids of the sequence (SEQ ID NO:5): Val Ala Gly Ser Asp Ala Gly Arg Ala Leu Gly Val Leu Ser Val Val Cys Leu Leu His Cys Phe Gly Phe Ile Ser Cys Phe Ser Gln Gln Ile Tyr Gly Val Val Tyr Gly Asn Val Thr Phe His Val Pro Ser Asn Val Pro Leu Lys Glu Val Leu Trp Lys Lys Gln Lys Asp Lys Val Ala Glu Leu Glu Asn Ser Glu Phe Arg Ala Phe Ser Ser Phe Lys; Y is hydroxyl or a polypeptide of the following amino acid sequence or a portion thereof consisting of the amino terminal 1 to 32 amino acids of the sequence (SEQ ID NO:33): Ser Leu Thr Ile Tyr Asn Leu Thr Ser Ser Asp Glu Asp Glu Tyr Glu Met Glu Ser Pro Asn Ile Thr Asp Thr Met Lys Phe Phe Leu Tyr Val; said polypeptide being capable of binding to CD2; (b) a polypeptide having the amino acid sequence: X.sub.1 -X.sub.2 -(SEQ ID NO:1) Asn Arg Val Tyr Leu Asp Thr Val Ser Gly-Y, wherein: X.sub.1 if present, is hydrogen or methionyl; X.sub.2, if present, is a polypeptide having the following amino acid sequence or a portion thereof consisting of the carboxy terminal 1 to 50 amino acids of the sequence (SEQ ID NO:2): Phe Ser Gln Gln Ile Tyr Gly Val Val Tyr Gly Asn Val Thr Phe His Val Pro Ser Asn Val Pro Leu Lys Glu Val Leu Trp Lys Lys Gln Lys Asp Lys Val Ala Glu Leu Glu Asn Ser Glu Phe Arg Ala Phe Ser Ser Phe Lys; Y is hydroxyl or a polypeptide of the following amino acid sequence or a portion thereof consisting of the amino-terminal 1 to 10 amino acids of the sequence (SEQ ID NO:3): Ser Leu Thr Ile Tyr Asn Leu Thr Ser Ser; said polypeptide being capable of binding to CD2; (c) a polypeptide having the amino acid sequence of amino acids 29-120 of SEQ ID NO:10; (d) a polypeptide having the amino acid sequence of amino acids 29-108 of SEQ ID NO:10; (e) a polypeptide having the amino acid sequence of amino acids 48-108 of SEQ ID NO:10; and (f) a polypeptide having the amino acid sequence of (SEQ ID NO:7): Lys Asn Arg Val Tyr Leu Asp Thr Val Ser Gly Ser Leu Thr Ile Tyr, and having a carboxy terminal region comprising a domain of a protein or polypeptide other than LFA-3. 6. The method of claim 5, wherein the domain of a protein or polypeptide other than LFA-3 that comprises the carboxy terminal region of the fusion protein comprises at least a portion of the Fc region of an immunoglobulin. 7. The method of claim 6 wherein the Fc region comprises a hinge region and C.sub.H 2 and C.sub.H 3 constant domains. 8. The method of claim 6 wherein the Fc region comprises a portion of a hinge region that is capable of forming intermolecular disulfide bonds and C.sub.H 2 and C.sub.H 3 constant domains. 9. The method of claim 5 wherein the fusion protein has amino acids 29-347 of SEQ ID NO:43.

Details for Patent 5,728,677

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Astellas Pharma Us, Inc.	AMEVIVE	alefacept	For Injection	125036	01/30/2003		2015-03-17

International Patent Family for US Patent 5,728,677

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	9216622
United States of America	5928643
United States of America	5914111
United States of America	5547853