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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Flagrante Delictu who wrote (15711)	2/23/1998 3:12:00 PM
From: Henry Niman	Read Replies (2) \| Respond to of 32384

Bernie, In Chicago, I just took undergraduate classes. My animal work began in La Jolla, at Scripps Clinic. I made monoclonal antibodies, and therefore I was a Mouse Man. Researchers interested in a "quicky" went after the bunnies. They only had to make an injection and then bleed the bunnies. For the mice, they had to be tested after the injections, then the spleens had to be harvested, cells fused to myelomas, and then screened for monoclonals. After the monoclonals were identified, then the real work began. My most famous monoclonal was one of the flu antibodies. It really became contagious and is used by almost every molecular research department in the world.

To: Flagrante Delictu who wrote (15711)	2/23/1998 3:16:00 PM
From: Henry Niman	Respond to of 32384

Here's the abstract for the flu monoclonal: Proc Natl Acad Sci U S A 1983 Aug;80(16):4949-4953 Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition. Niman HL, Houghten RA, Walker LE, Reisfeld RA, Wilson IA, Hogle JM, Lerner RA Recent studies have shown that chemically synthesized small peptides can induce antibodies that often react with intact proteins regardless of their position in the folded molecule. These findings are difficult to explain in view of the experimental and theoretical data which suggest that in the absence of forces provided by the folded protein, small peptides in aqueous solution do not readily adopt stable structures. In order to rationalize the two findings, there has been general acceptance of a stochastic model which suggests that the multiple conformers of a peptide in solution induce sets of antibodies with a small percentage reactive with conformations shared by the folded protein. This stochastic model has become less tenable as the success rate for the generation of protein-reactive anti-peptide antibodies has grown. To test the stochastic model, we have used monoclonal anti-peptide antibodies as a way of estimating the frequency with which small peptides induce antibodies that react with folded proteins. We have made monoclonal antibodies to six chemically synthesized peptides from three proteins. The frequency with which the peptides induce protein-reactive antibodies is at least 4 orders of magnitude greater than expected from previous experimental work and vastly different from what would be predicted by calculating the possible number of peptide conformers in solution. These findings make the stochastic model less likely and lead to consideration of other models. Aside from their practical significance for generation of highly specific reagents, these findings may have important implications for the protein folding problem. PMID: 6192445, UI: 83273731

To: Flagrante Delictu who wrote (15711)	2/23/1998 3:20:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's one of the associated patents: United States Patent 5,030,565 Niman, et. al. Jul. 9, 1991 Polypeptide-induced monoclonal receptors to protein ligands Inventors: Niman; Henry L. (Carlsbad, CA); Lerner; Richard A. (La Jolla, CA). Assignee: Scripps Clinic and Research Foundation (La Jolla, CA). Appl. No.: 701,954 Filed: Feb. 15, 1985 Related U.S. Application Data Continuation-in-part of Ser No. 1,304, Aug. 17, 1984, which is a continuation-in-part of Ser. No. 524,084, Aug. 17, 1983, abandoned. Intl. Cl. : G01N 33/577 Current U.S. Cl.: 530/387.7; 422/61; 435/172.2; 435/240.27; 435/70.21; 436/548; 436/813; 530/324; 530/325; 530/326; 530/327; 530/328; 530/329; 530/387.9; 530/388.85; 530/413 Field of Search: 435/68, 172.2, 240, 70.21, 240.27; 436/548, 813; 530/387, 324-329, 413; 422/61 References Cited \| [Referenced By] U.S. Patent Documents 4,532,220 Jul., 1985 Lavi 436/813 X 4,535,058 Aug., 1985 Weinberg 436/813 X 4,699,877 Oct., 1987 Cline 435/6 Foreign Patent Documents 8403087 Aug., 1984 WO 103/52 Other References Gentry et al., J. Biol. Chem., 258:11219-11228 (1983). Tamura et al., Cell 34:587-596 (1983). Arneheiter et al., Nature 294:278-380 (1981). Gonda, T. J. et al., Molecular and Cellular Biology, 2(6), 617-624 (Jun. 1982). Der, C. J. et al., Proc. Natl. Acad. Sci., U.S.A., 79(11), 3637-3640 (Jun. 1982). Furth, M. E. et al., J. Virol., 43(1), 294-304 (Jul. 1982). Chemical Abstracts, 98:103976a (Mar. 1983). Chemical Abstracts, 99:137927w (Oct. 1983). Young and Atassi, Immunological Communications 11(1):9-16 (Jul. 23, 1982). Schmitz, Atassi and Atassi, Molecular Immunology 19:1699-1702 (Dec. 1982). Sutcliffe et al., Science 219:660-666 (Feb. 11, 1983). Bulinski, International Review of Cytology 103:281-303 (1986). Niman et al., PNAS-U.S.A. 80:4949-4953 (1983). Newmark News and Views, Nature 305:9 (Sept. 1983). Baltimore, TBIS 9:137-138 (Apr. 1984). Sutcliffe et al., Nature 287:801-805 (Oct. 1980). Sen et al., PNAS-USA 80:1246-1250 (Mar. 1980). Wong and Goldberg PNAS-USA 78:7412-7416 (Dec. 1981). Papkoff et al., Cell 27:109-119 (Nov. 1981). Papkoff et al., Cell 29:417-426 (Jun. 1982). Tamura and Bauer, EMBO J. 1:1479-1485 (1982). Primary Examiner: Nucker; Christine Attorney, Agent or Firm: Lyon & Lyon Abstract Monoclonal receptors raised to immunogenic polypeptides whose amino acid residue sequences correspond to sequences of oncoprotein ligands are disclosed, as are method for the production of those receptors and products and methods that utilize them. The monoclonal receptors bind both to the oncoprotein ligand to a portion of which the polypeptide corresponds in sequence, and to the immunogenic polypeptide to which the receptors were raised. 31 Claims, 16 Drawing Figures

To: Flagrante Delictu who wrote (15711)	2/23/1998 3:28:00 PM
From: Henry Niman	Respond to of 32384

Here's another one: United States Patent 5,015,571 Niman, et. al. May 14, 1991 Polypeptide-induced monoclonal receptors to protein ligands Inventors: Niman; Henry L. (Carlsbad, CA); Lerner; Richard A. (La Jolla, CA). Assignee: Scripps Clinic and Research Foundation (La Jolla, CA). Appl. No.: 39,534 Filed: Apr. 16, 1987 Related U.S. Application Data Continuation-in-part of Ser No. 736,545, May 21, 1985, which is a continuation-in-part of Ser. No. 701,954, Feb. 15, 1985, and a continuation-in-part of Ser No. 713,410, Feb. 15, 1985, abandoned, which is a continuation-in-part of Ser. No. 524,084, Aug. 17, 1983, abandoned. Intl. Cl. : C12Q 1/00 Current U.S. Cl.: 435/7.92; 436/501; 436/510; 436/811; 436/814 Field of Search: 435/7; 436/811, 814 References Cited \| [Referenced By] Primary Examiner: Wax; Robert A. Assistant Examiner: Stucker; J. Attorney, Agent or Firm: Lyon & Lyon Abstract Monoclonal receptors raised to immunogenic polypeptides whose amino acid residue sequences correspond to sequences of oncoprotein ligands are disclosed, as are method for the production of those receptors and products and methods that utilize them. The monoclonal receptors bind both to the oncoprotein ligand to a portion of which the polypeptide corresponds in sequence, and to the immunogenic polypeptide to which the receptors were raised. 9 Claims, 24 Drawing Figures The U.S. Government has rights in this invention pursuant to Public Health Service Contract N01-CP-41009, Public Health Service Grants CA 38160 and CA25803.