Humanized immunoglobulin loci

التفاصيل البيبلوغرافية
العنوان: Humanized immunoglobulin loci
Patent Number: 7,585,668
تاريخ النشر: September 08, 2009
Appl. No: 10/893483
Application Filed: July 15, 2004
مستخلص: The present invention concerns methods and means to produce humanized antibodies from transgenic non-human animals. The invention specifically relates to novel immunoglobulin heavy and light chain constructs, recombination and transgenic vectors useful in making transgenic non-human animals expressing humanized antibodies, transgenic animals, and humanized immunoglobulin preparations.
Inventors: Buelow, Roland (Palo Alto, CA, US); van Schooten, Wim (Sunnyvale, CA, US); Platzer, Josef (Geretsried, DE)
Assignees: Therapeutic Human Polyclonals, Inc. (Mountain View, CA, US)
Claim: 1. An isolated nucleic acid molecule comprising two or more identical units consisting of, from 5′ to 3′ direction, a 5′ nucleotide sequence, a human immunoglobulin heavy chain V gene segment, and a 3′ nucleotide sequence, wherein said 5′ nucleotide sequence and said 3′ nucleotide sequence are identical or different, and comprise 20 to 1000 contiguous nucleotides of a spacer sequence from an immunoglobulin heavy chain gene of an animal generating antibody diversity primarily by gene conversion and/or hypermutation, wherein said spacer sequence is SEQ ID NO: 35, and said animal is a rabbit.
Claim: 2. The isolated nucleic acid molecule of claim 1 wherein said human immunoglobulin heavy chain V gene segment is a member of the VH3, VH1, VH5, or VH4 family.
Claim: 3. A recombination vector comprising a nucleic acid molecule according to claim 1 .
Current U.S. Class: 4353/201
Patent References Cited: 0 491 057 July 1991
0 583 980 August 1993
WO 92/03918 March 1992
WO 97/16537 May 1997
WO 00/46251 August 2000
WO 00/75300 December 2000
WO 01/19394 March 2001
WO 02/12437 February 2002
WO 02/12437 February 2002
WO 2004/003157 August 2004


























Other References: Gallarda et al. (1985) J. Immunol., vol. 135 (6) 4222-4228. cited by examiner
Brüggemann et al., “A Repertoire of Monoclonal Antibodies with Human Heavy Chains from Transgenic Mice”, Proceedings of the National Academy of Sciences USA, vol. 86, No. 17, pp. 6709-6713, Sep. 1, 1989. cited by other
Brüggemann et al., “Strategies for expressing human antibody repertoires in transgenic mice”, Immunology Today, vol. 17, No. 8, pp. 391-397, Aug. 1, 1996. cited by other
Jakobovitis et al., “Analysis of Homozygous Mutant Chimeric Mice: Deletion of the Immunoglobin Heavy-Chain Joining Region Blocks B-Cell Development and Antibody Production”, Proceedings of the National Academy of Sciences USA, vol. 90, No. 6, pp. 2551-2555, Mar. 1, 1993. cited by other
Ros et al.,, “Sequence Analysis of 0.5 Mb of the rabbit germline immunoglobin heavy chain locus”, Gene: An International Journal on Genes and Genomes, vol. 330, No. 14, pp. 49-59, Apr. 14, 2004. cited by other
Hesse et al., “V(D)J Recombination: A Functional Definition of the Joining Signals” Genes and Development, Cold Spring Harbor Laboratory Press, Plainview, NY, US, vol. 3, No. 7, (1989), pp. 1053-1061 XP009043633 ISSN: 0890-9369. cited by other
Database EMBL Jul. 16, 1998 (Jul. 16, 1988), “rabbit Ig Germline CL42.Vh25 and CL. 42Vh34 Genes, VHA3 Allotype, 5′end” XP002393777 retrieved from EBI Database Accession No. M12180. cited by other
Volgina et al., “A Single 3′α hs1,2 Ehancer in the rabbit IgH Locus” Journal of Immunology 165:6400-6405 (2000). cited by other
Yu et al., “An Efficient Recombination System for Chromosome Engineering in Escherichia Coli” PNAS, vol. 97, No. 11, pp. 5987-5983 (2000). cited by other
Zhang et al., “Risk of Tuberculosis Infection and Tuberculous Meningitis after Discontinuation of Bacillus Calmette-Guerin in Beijing” Am J Respir Crit Care Med 162:1314-1317 (2000). cited by other
Muyrers et al., “Rapid Modification of Bacterial Artificial Chromosomes by ET-recombination” Nucleic Acids Research 27(6):1555-15557 (1997). cited by other
Butler, “Immunoglobulin Diversity, B-cell and Antibody Repertoire Development in Large Farm Animals” Rev. Sci. Tech. Off. int. Epiz. 17(1):43-70 (1998). cited by other
Reynaud et al., “Somatic Hyperconversion Diversifies the Single VH Gene of the Chicken with a High Incidence in the D Region” Cell 59:171-183 (1989). cited by other
Lee et al., “A Highly Efficient Escherichia Coli-Based Chromosome Engineering System Adapted for Recombination Targeting and Subcloning of BAC DNA” Genomics 73:56-65 (2001). cited by other
Hole et al., “Identification of Enhancer Sequences 3′ of the Rabbit Ig KL Chain Loci” The Journal of Immunology 146(12):4377-4384 (1991). cited by other
Lauster et al., “Promotor, Enhancer and Silencer Elements Regulate Rearrangement of an Immunoglobulin Transgene” EMBO Journal 12(12):4615-4623 (1993). cited by other
Mansikka et al., “Bursectomy of Chicken Embryos at 60 Hours of Incubation Leads to an Oligoclonal B Cell Compartment and Restricted Ig Diversity” Journal of Immunology ,145(11):3601-3609 (1990). cited by other
Muyrers et al., “Techniques: Recombinogenic Engineering-New Options for Cloning and Manipulating DNA” Trends in Biochemical Sciences, 26(5):325-331 (2001). cited by other
Pain et al., “Chicken Embryonic Stem Cells and Transgenic Strategies” Cell Tissues, 165:212-219 (1999). cited by other
Reynaud et al., “Hypermutation Generating the Sheep Immunoglobulin Repertoire is an Antigen-Independent Process” Cell, 80:115-125 (1995). cited by other
Dufour et al., “The Sheep Ig Variable Region Repertoire Consists of Single VH Family” Journal of Immunology, 156:2163-2170 (1996). cited by other
Sang, “Transgenic Chicken-Methods and Potential Applications” Tibtech, 12:415-420 (1994). cited by other
Sherman et al., “Transposition of the Drosophila Element Mariner into the Chicken Germ Line” Nature Biotechnology, 16:1050-1053 (1998). cited by other
Genbank, AY495827, Platzer, J., Direct Submission: Nov. 2003.THP Gmbh, Am Neuland 3, Bernried 82347 Germany. cited by other
Genbank, AY495828, Platzer, J., “Sequence Analysis of 0.4 Megabases of the rabbit Germline Immunoglobulin Kappal Light Chain Locus” Direct Submission: Nov. 2003. THP Gmbh, Am Neuland 3, Bernried 82347 Germany. cited by other
Genabnk, AY495826, Platzer, J., Direct Submission: Nov. 2003. THP Gmbh, Am Neuland 3, Bernried 82347 Germany. cited by other
Etches, R.J., et al., Strategies for the Production of Transgenic Chickens, Methods in Molecular Biology—62:433-450 (1997). cited by other
Primary Examiner: Wehbe, Anne Marie S
Attorney, Agent or Firm: Dreger, Ginger R.
Goodwin Procter LLP
رقم الانضمام: edspgr.07585668
قاعدة البيانات: USPTO Patent Grants