Byoung Se Kwon

US Patent:

6355476, Mar 12, 2002

Filed:

Jul 30, 1992

Appl. No.:

07/922996

Inventors:

Byoung Se Kwon - Carmel IN
Hal E. Broxmeyer - Indianapolis IN

Assignee:

Advanced Research and TechnologyInc - Indianapolis IN

International Classification:

C07K 1452

US Classification:

4353201, 435 691, 536 231, 536 235, 530300, 530324

Abstract:

Full length cDNAs, L2G25B and 4-1BB, were isolated and sequenced. The cDNA L2G25B encodes for the lymphokine, macrophage inflammatory protein-1 or MIP-1. The studies disclosed herein suggest that MIP-1 and MIP- can, through rapid action, modulate early myeloid progenitor cell proliferation. Recombinant proteins have been produced for the cytokine, L2G25BP (Macrophage Inflammatory Protein-1, MIP-1). By employing the recombinant protein (rMIP-1), receptors for MIP-1 were identified on Con A-stimulated and unstimulated CTLL-R8, a T-cell line, and LPS-stimulated RAW 264. 7, a macrophage-cell line. Purified recombinant murine macrophage inflammatory protein-1 alpha (rmuMIP-), was assessed for effects on proliferation of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. The results suggest that rmuMIP-1 has myelosuppressive activity in vivo. The cDNA clone, called 4-1BB, is an inducible receptor-like sequence found in both cytolytic and helper T-cells.

US Patent:

6362325, Mar 26, 2002

Filed:

Feb 1, 1993

Appl. No.:

08/012269

Inventors:

Byoung S. Kwon - Carmel IN

Assignee:

Advanced Research and Technology Institute, Inc. - Indianapolis IN

International Classification:

C07H 2104

US Classification:

536 235, 435 6, 435 72, 435 691, 435 695, 530350, 530351, 436501

Abstract:

The present invention includes the receptor protein 4-1BB and the cDNA gene encoding for receptor protein 4-1BB. The nucleotide sequence of the isolated cDNA is disclosed herein along with the deduced amino acid sequence. The 4-1BB protein and fragments and derivatives can be used: 1) as a probe to isolate ligands to receptor protein 4-1BB, 2) to stimulate proliferation of B-cells expressing 4-1BB, or 3) to block 4-1BB ligand binding. A monoclonal antibody against 4-1BB was developed which specifically recognizes an epitope on the extracellular domain of receptor protein 4-1BB. The monoclonal antibody can be used enhance T-cell proliferation and activation by treating T-cells that have expressed receptor protein 4-1BB with the monoclonal antibody. The effectiveness of the treatment was enhanced when conducted in the presence of protein tyrosinase kinase. A fusion protein for detecting cell membrane ligands to receptor protein 4-1BB was developed.

US Patent:

6569997, May 27, 2003

Filed:

May 25, 2000

Appl. No.:

09/578764

Inventors:

Byoung S. Kwon - Carmel IN

Assignee:

Advanced Research and Technology Institute, Inc. - Bloomington IN

International Classification:

C07K 1600

US Classification:

53038822, 530350, 514 2, 514 44, 514100, 536 235, 436501, 435 6, 435 72, 435 721, 435 691, 435 695, 4352523, 43524027, 4241301, 4241841

Abstract:

Disclosed herein are the methods of using the H4-1BB protein, ligands to this protein, and various mAbs either directed against H4-1BB or other molecules that can be used therapeutically. The nature and importance of the H4-1BB molecule provides the ligands and related co-stimulatory molecules the ability to enhance or suppress T-cell activation and proliferation. By treating T-cells that have expressed receptor protein H4-1BB with one of the four anti-H4-1BB monoclonal antibodies disclosed herein activation or inhibition of the immune response is seen. Also disclosed herein is cDNA for the human receptor H4-1BB. The cDNA of the human receptor H4-1BB is about 65% homologous to the mouse cDNA 4-1BB and was isolated by using probes derived from murine cDNA 4-1BB. A fusion protein for detecting cell membrane ligands to human receptor protein H4-1BB was developed. It comprises the extracellular portion of the receptor protein H4-1BB and a detection protein, alkaline phosphatase, bound to the portion of the receptor protein H4-1BB.

US Patent:

6692735, Feb 17, 2004

Filed:

Jul 21, 1999

Appl. No.:

09/355193

Inventors:

Byoung S. Kwon - Carmel IN
Byung S. Youn - Seoul, KR
Soo-Il Chung - Kyounggi-do, KR
Doo-Hong Park - Seoul, KR
Seung Jae Baek - Kyounggi-do, KR
Eun-Kyoung Lee - Seoul, KR
Ju-Hyung Ahn - Kyounggi-do, KR
Kong-Ju Lee - Kyounggi-do, KR

Assignee:

Korea Green Cross Corporation - Kyounggi-do
Mogam Biotechnology Research Institute - Kyounggi-do

International Classification:

C07K 1452

US Classification:

424 851, 530324, 435 695, 435 711, 435 712, 435471, 4353201, 4352523, 4352555

Abstract:

The present invention relates to a variant of Lkn-1(shLkn-1) with enhanced biological activity, which is a truncated form of Lkn-1, a process for preparing a recombinant shLkn-1 by employing expression vector therefor and pharmaceutical application of the said protein. shLkn-1 is generated by missing 26 amino acid residues from the amino terminus of Lkn-1 to contain 66 amino acids. Recombinant shLkn-1 inhibits colony formation and cell proliferation in vivo, which suggests that it can be used as a potential drug for the antibody production, the treatment during HIV-1 infection, the protection of bone marrow stem cells during chemotherapy or radiotherapy, and the inhibition of leukemia.

US Patent:

6905685, Jun 14, 2005

Filed:

Jun 8, 2001

Appl. No.:

09/877338

Inventors:

Byoung S. Kwon - Carmel IN, US

International Classification:

A61K039/395
C07K016/00
C07K014/00

US Classification:

4241381, 5303871, 5303881, 5302891, 530350, 4241391

Abstract:

Disclosed herein are the methods of using the H4-1BB protein, ligands to this protein, and various mAbs either directed against H4-1BB or other molecules that can be used therapeutically. The nature and importance of the H4-1BB molecule provides the ligands and related co-stimulatory molecules the ability to enhance or suppress T-cell activation and proliferation. By treating T-cells that have expressed receptor protein H4-1BB with one of the four anti-H4-1BB monoclonal antibodies disclosed herein activation or inhibition of the immune response is seen. Also disclosed herein is cDNA for the human receptor H4-1BB. The cDNA of the human receptor H4-1BB is about 65% homologous to the mouse cDNA 4-1BB and was isolated by using probes derived from murine cDNA 4-1BB. A fusion protein for detecting cell membrane ligands to human receptor protein H4-1BB was developed. It comprises the extracellular portion of the receptor protein H4-1BB and a detection protein, alkaline phosphatase, bound to the portion of the receptor protein H4-1BB.

US Patent:

6974863, Dec 13, 2005

Filed:

Feb 4, 2002

Appl. No.:

10/067122

Inventors:

Byoung S. Kwon - Carmel IN, US

Assignee:

Indiana University Research and technology Corporation - Indianapolis IN

International Classification:

C07K001/00
C07H021/04
C12N001/20
C12P021/06
G01N033/567

US Classification:

53038822, 530300, 530350, 435 721, 435 691, 435 695, 436501, 536 235, 514 2

Abstract:

The present invention includes the receptor protein 4-1BB and the cDNA gene encoding for receptor protein 4-1BB. The nucleotide sequence of the isolated cDNA is disclosed herein along with the deduced amino acid sequence. The 4-1BB protein and fragments and derivatives can be used: 1) as a probe to isolate ligands to receptor protein 4-1BB, 2) to stimulate proliferation of B-cell's expressing 4-1BB, or 3) to block 4-1BB ligand binding. A monoclonal antibody against 4-1BB was developed which specifically recognizes an epitope on the extracellular domain of receptor protein 4-1BB. The monoclonal antibody can be used enhance T-cell proliferation and activation by treating T-cells that have expressed receptor protein 4-1BB with the monoclonal antibody. The effectiveness of the treatment was enhanced when conducted in the presence of protein tyrosinase kinase. A fusion protein for detecting cell membrane ligands to receptor protein 4-1BB was developed.

US Patent:

8026353, Sep 27, 2011

Filed:

Dec 20, 2001

Appl. No.:

10/027199

Inventors:

Byoung S. Kwon - Metairie LA, US

Assignee:

Indiana University Research and Technology Corporation - Indianapolis IN

International Classification:

C07H 21/04
C12P 21/06
C12N 1/20
C12N 5/00
C12N 5/02
C12N 15/74

US Classification:

536 235, 435 691, 4353201, 435325, 435471

Abstract:

The human receptor H4-1BB has been isolated, sequenced and disclosed herein. The cDNA of the human receptor H4-1BB is about 65% homologous to the mouse cDNA 4-1BB and was isolated by using probes derived from cDNA 4-1BB. A fusion protein for detecting cell membrane ligands to human receptor protein H4-1BB was developed. It comprises the extracellular portion of the receptor protein H4-1BB and a detection protein (alkaline phosphatase) bound to the portion of the receptor protein H4-1BB. B-cells that have expressed a ligand to receptor protein H4-1BB can be treated with cells that have expressed receptor protein H4-1BB and B-cell proliferation may be induced. The use of H4-1BB to block H4-1BB ligand binding has practical application in the suppression of the immune system during organ transplantation. A monoclonal antibody against H4-1BB can be used to enhance T-cell proliferation by treating T-cells that have expressed receptor protein H4-1BB with the anti H4-1BB monoclonal antibody. Tumors transfected with H4-1BBL may be capable of delivering antigen-specific signals as well as the co-stimulatory signals and can be killed by human cytotoxic T lymphocytes.

US Patent:

20060029595, Feb 9, 2006

Filed:

Apr 18, 2005

Appl. No.:

11/108257

Inventors:

Byoung Kwon - Carmel IN, US

International Classification:

A61K 39/395

US Classification:

424130100, 424144100

Abstract:

Disclosed herein are the methods of using the H4-1BB protein, ligands to this protein, and various mAbs either directed against H4-1BB or other molecules that can be used therapeutically. The nature and importance of the H4-1BB molecule provides the ligands and related co-stimulatory molecules the ability to enhance or suppress T-cell activation and proliferation. By treating T-cells that have expressed receptor protein H4-1BB with one of the four anti-H4-1BB monoclonal antibodies disclosed herein activation or inhibition of the immune response is seen. Also disclosed herein is cDNA for the human receptor H4-1BB. The cDNA of the human receptor H4-1BB is about 65% homologous to the mouse cDNA 4-1BB and was isolated by using probes derived from murine cDNA 4-1BB. A fusion protein for detecting cell membrane ligands to human receptor protein H4-1BB was developed. It comprises the extracellular portion of the receptor protein H4-1BB and a detection protein, alkaline phosphatase, bound to the portion of the receptor protein H4-1BB. B-cells that have expressed a ligand to receptor protein H4-1BB can be treated with cells that have expressed receptor protein H4-1BB and B-cell proliferation may be induced. The use of H4-1BB to block H4-1BB ligand binding has practical application in the suppression of the immune system during organ transplantation or against autoimmune diseases including diabetes, rheumatoid arthritis, and lupus. Other applications of this technology include the development of therapeutic methods for the treatment of HIV-1 infected individuals, and the treatment of cancerous tumors.