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USOO7745.391 B2 (12) United States Patent (10) Patent No.: US 7,745,391 B2 Mintz et al. (45) Date of Patent: Jun. 29, 2010 (54) HUMAN THROMBOSPONDIN POLYPEPTIDE 5,283,317. A 2/1994 Saifer et al. 5,288,514. A 2/1994 Ellman (75) Inventors: Liat Mintz, East Brunswick, NJ (US); 5,328,470 A 7, 1994 Nabel et al. Hanging Xie, Lambertville, NJ (US); 5,384,261 A 1/1995 Winkler et al. Dvir Dahary, Tel-Aviv (IL); Erez 5,459,039 A 10/1995 Modrich et al. Levanon, Petach-Tikva (IL), Shiri 5,475,092 A 12/1995 Charietal. Freilich, Herzlia (IL); Nili Beck, Kfar 5,498,531 A 3, 1996 Jarrell Saba (IL); Wei-Yong Zhu, Plainsboro, 5,510,270 A 4/1996 Fodor et al. E"ESNI)s s 379- J. A ROMomoglio is et al.a (73) Assignee: Compugen Ltd., Tel-Aviv (IL) 5,585,089 A 12/1996 Queen et al. 5,585.499 A 12/1996 Chari et al. (*) Notice: Subject to any disclaimer, the term of this 5,631, 169 A 5/1997 Lakowicz et al. patent is extended or adjusted under 35 5,693,761 A 12/1997 Queen et al. U.S.C. 154(b) by 441 days. 5,693,762. A 12/1997 Queen et al. 5,695,937 A 12/1997 Kinzler et al. (21) Appl. No.: 11/443,428 5,846,545. A 12/1998 Chari et al. 5,854,033. A 12/1998 Lizardi (22) Filed: May 31, 2006 5,876,742 A 3/1999 Cochrum et al. (Under 37 CFR 1.47) 6,033,862. A 3/2000 Matsuda et al. (65) Prior Publication Data 6,049,728 A 4/2000 Chou et al. 6,727,063 B1 4/2004 Lander et al. .................. 435/6 US 2007/0083334 A1 Apr. 12, 2007 7,223,731 B2 * 5/2007 Lawler ............. ... 514/12 7.368,548 B2 * 5/2008 Dahary et al. .............. 536,231 Related U.S. Application Data 2002fO155615 A1 10, 2002 Novikov et al. (63) Continuation of application No. 10/242,799, filed on 2003.0118585 A1 6, 2003 Muller et al. Sep. 13, 2002, now abandoned. 2003/0176666 A1 9, 2003 Sutcliffe et al. (60) Provisional application No. 60/397,784, filed on Jul. 2004.0054268 A1 3, 2004 Esenaliev et al. 24, 2002, provisional application No. 60/384,096, 2004/0101876 A1 5, 2004 Mintz et al. filed on May 31, 2002, provisional application No. 2004/O127777 A1 7, 2004 Ruchiti et al. 60/371,494, filed on Apr. 11, 2002, provisional appli- 2004/O142325 A1 7, 2004 Mintz et al. cation No. 60/354.242, filed on Feb. 6, 2002, provi- 2004/0248157 Al 12/2004 Ayalon-Soffer et al. sional application No. 60/324,524, filed on Sep. 26, 2004/0265799 A1 12, 2004 Novik et al. 2001, provisional application No. 60/322,506, filed on 2005/O123538 A1 6/2005 Shemesh et al. Sep. 14, 2001, provisional application No. 60/322,359, 2005, 0186600 A1 8, 2005 Sella-Tavor et al. filed on Sep. 14, 2001, provisional application No. 60/322.285, filed on Sep. 14, 2001. (51) Int. Cl. (Continued) A6 IK 38/00 (2006.01) C07K I4/00 (2006.01) FOREIGN PATENT DOCUMENTS (52) U.S. Cl. .............................. 514/2; 514/12:530/350 EP 125O23 11, 1984 (58) Field of Classification Search ....................... None See application file for complete search history. (56) References Cited (Continued) U.S. PATENT DOCUMENTS OTHER PUBLICATIONS 4,215,051 A 7, 1980 Schroeder et al. 4,683.202 A 7, 1987 Mullis Lawler et al., J. Cell. Biol. 103: 1635-1648, 1986.* 4,704,692 A 11, 1987 Ladner 4,816,567 A 3/1989 Cabilly et al. (Continued) 4,868,103 A 9/1989 Stavrianopoulos et al. 4,873,316 A 10, 1989 Meade et al. Primary Examiner David J Steadman 4.946,778 A 8, 1990 Ladner et al. 4,987,071 A 1/1991 Cech et al. (57) ABSTRACT 5,093,246 A 3, 1992 Cech et al. 5,116,742 A 5, 1992 Cech et al. 5,143,854 A 9, 1992 Pirrung A human thrombospondin 1 protein, polynucleotide encod 5,208,020 A 5, 1993 Chari et al. ing the protein, and pharmaceutical composition thereof 5,223,409 A 6/1993 Ladner et al. gune p , and p p 5,225,539 A 7, 1993 Winter 5,272,057 A 12/1993 Smulson et al. 2 Claims, 25 Drawing Sheets US 7,745,391 B2 Page 2 U.S. PATENT DOCUMENTS Akhurst “TGF-B Antagonists: Why Suppress ATumor Suppressor?’’. The Journal of Clinical Investigation, 109(12): 1533-1536, 2002. 2005/023396.0 A1 10/2005 Kong-Beltran et al. Altschul et al. “Basic Local Alignment Search Tool”, Journal of 2006, OO68405 A1 3, 2006 Diber et al. molecular Biology, 215: 403-410, 1990. 2007/0082337 A1 4/2007 Sorek et al. Asadullah et al. “Interleukin-10 Therapy-Review of A New Approach'. Pharmacological Review, 55(2): 241-269, 2003. FOREIGN PATENT DOCUMENTS Attisano et al. “Signal Transduction by the TGF-B Superfamily”. EP 1841.87 6, 1985 Science, 296(5573): 1646-1647, 2002. EP 171496 2, 1986 Audic et al. “The Significance of Digital Gene Expression Profiles'. EP 173494 3, 1986 Genome Research, 7: 986-995, 1997. EP O519596 12/1992 Azios et al. “Expression of Herstatin, An Autoinhibitor of HER-2/ EP O770349 5, 1997 Neu, Inhibits Transactivation of HER-3 by HER-2 and Blocks EGF GB 2322941 9, 1998 Activation of the EGF Receptor'. Oncogene, 20(37): 5199-5232, WO WO 86.01533 3, 1986 2001. WO WO90,02809 3, 1990 Baker et al. "A Randomized Phase 2 Study of the Thrombospondin WO WO91/00906 1, 1991 Mimetic. Peptide ABT-510 in Patients With Advanced Soft Tissue WO WO91,06667 5, 1991 Sarcoma (STS)”, Journal of Clinical Onoclogy, Proceedings of the WO WO91f10741 7, 1991 ASCO Annual Meeting 2005, 23(16 Suppl.): 9013, Jun. 1, 2005. WO WO 91f17271 11, 1991 Abstract. WO WO92fO1047 1, 1992 Benson et al. “GenBank”. Nucleic Acids Research, 25(1): 1-6, 1997. WO WO92fO3917 3, 1992 p. 1-5. WO WO92fO3918 3, 1992 Bieche et al. “Overexpression of BRCA2 Gene in Sporadic Breast WO WO92.09690 6, 1992 Tumours”. Oncogen, 18: 5232-5238, 1999. WO WO92, 15679 9, 1992 Bihl et al. “Identification of a Novel IL-6 Isoform Binding to the WO WO92, 18619 10, 1992 Endogenous IL-6 Receptor'. American Journal of Respiratory Cell WO WO92/2O791 11, 1992 and Molecular Biology, 27: 48-56, 2002. WO WO93/O1288 1, 1993 Birchmeier et al. “Met, Metastasis, Motility and More', Nature WO WO94f10300 5, 1994 Reviews: Molecular Cell Biology, 4:915-925, 2003. WO WO 98.55510 12/1998 Blazar et al. “Ligation of 4-IBB (CDw137) Regulates Graft-Versus WO WO99, 18208 4f1999 Host Disease, Graft-Versus-Leukemia, and Graft Rejection in WO WO 99.51773 10, 1999 Allogeneic Bone Marrow Transplant Recipients'. The Journal of WO WO O2, 12341 2, 2002 Immunology, 166(5): 3174-3183, 2001. WO WO 03/020953 3, 2003 Boguski"Biosequence Exegesis”. Science, 286: 453-455, 1999. WO WO 2004/092.338 10, 2004 Boguski et al. “ESTablishing A Human Transcript Map”. Nature WO WO 2004/096979 11, 2004 WO WO 2004/096.980 11, 2004 Genetics, 10: 369-371, 1995. WO WO 2005/033133 4/2005 Bonfield etal. “A New DNA Sequence Assembly Program'. Nucleic WO WO 2005/0686.18 7/2005 Acids Research, 23(24): 4992-4999, 1995. WO WO 2005/071058 8, 2005 Bornstein “Diversity of Function Is Inherent in Matricellular Pro WO WO 2005/071059 8, 2005 teins: An Appraisal of Thrombospondin 1'. The Journal of Cell WO WO 2005,111634 11, 2005 Biology, 130(3): 503-506, Aug. 1995. WO WO 2005,113596 12/2005 Bornstein “Thrombospondins: Structure and Regulation of Expres sion'. The FASEB Journal, 6:3290-3299, 1992. Brattain et al. “The Type II Transforming Growth Factor-B Receptor OTHER PUBLICATIONS as A Tumor-Suppressor Gene'. Current Opinion in Oncology, 8(1): Chen et al., Mol Cell Prot 1:304-313, 2002.* 49-53, 1996. Tolsma et al., J. Cell Biol. 122:497-511, 1993.* Brett et al. “EST Comparison Indicates 3.8% of Human mRNAs Chen et al., Biochemistry 37.9976-9982, 1998.* Contain Possible Alternative Splice Forms', FEBS Letters, 474: “Agencourt 6578352 NIH MGC 41 Homo Sapiens cDNA Clone 83-86, 2000. IMAGE: 5467535 5", mRNA Sequence”, Database EMBL'Online!, Brierley etal. “IFN-O/B Receptor Interactions to Biologic Outcomes: Database Accession No. BM556795, 2002. Understanding the Circuitry”, Journal of Interferon and Cytokine “Agencourt 785234 NIH MGC 67 Homo Sapiens cDNA Clone Research, 22(8): 835-845, 2002. IMAGE: 61400985", mRNA Sequence”, Database EMBL'Online!, Brockmann et al. "Inhibition of Intracerebral Glioblastoma Growth Database Accession No. BU169315, 2002. by Local Treatment With the Scatter Factor/Hepatocyte Growth Fac “Agencourt 7952308 NIH MGC 72 Homo Sapiens cDNA Clone tor-Antagonist NK4'. Clinical Cancer Research, 9: 4578-4585, IMAGE: 6149711 5", mRNA Sequence”, Database EMBL'Online!, 2003. Database Accession No. BU171488, 2002. Buetow etal. “High-Throughput Development and Characterization “OTTHUMP00000031654 (Fragment), Database EMBL, Database of A Genomewide Collection of Gene-Based Single Nucleotide Accession No. Q9BQP0, 2001. Abstract. Polymorphism Markers by Chip-Based Matrix-Assisted Laser Abounader et al. “In Vivo Targeting of SF/HGF and C-Met Expres Desorption/Ionization Time-of-Flight Masss Spectrometry”. Proc. sion Via U1snRNA/Ribozymes Inhibits Glioma Growth and Natl. Acad. Sci. US, 98(2): 581-584, 2001. Esp. p. 581-583 A. Angiogenesis and Promotes Apoptosis'. The FASEB Journal, 16: Burgess et al.
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    bioRxiv preprint doi: https://doi.org/10.1101/2020.05.18.102244; this version posted May 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Awakening a latent carbon fixation cycle in Escherichia coli Ari Satanowski1‡, Beau Dronsella1‡, Elad Noor2, Bastian Vögeli3, Hai He1, Philipp Wichmann1, Tobias J. Erb3,4, Steffen N. Lindner1*, Arren Bar-Even1* 1Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam, Germany. 2Institute of Molecular Systems Biology, ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland. 3Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Straße 10, 35043 Marburg, Germany. 4Center for Synthetic Microbiology (SYNMIKRO), 35043 Marburg, Germany. ‡ These authors contributed equally to this study. * Corresponding authors: Arren Bar-Even: phone: +49 331 567-8910; Email: [email protected] Steffen N. Lindner: phone: +49 331 567-8149; Email: [email protected] Keywords: metabolic engineering; synthetic biology; reductive carboxylation; NADPH biosynthesis; modular engineering approach. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.05.18.102244; this version posted May 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Carbon fixation is one of the most important biochemical processes.

  • BMC Structural Biology Biomed Central

    BMC Structural Biology BioMed Central Research article Open Access A comprehensive update of the sequence and structure classification of kinases Sara Cheek2, Krzysztof Ginalski2,3, Hong Zhang2 and Nick V Grishin*1,2 Address: 1Howard Hughes Medical Institute, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd., Dallas, Texas 75390, USA, 2Department of Biochemistry, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd., Dallas, Texas 75390, USA and 3Bioinformatics Laboratory, Interdisciplinary Centre for Mathematical and Computational Modelling Warsaw University, Pawinskiego 5a, 02-106 Warsaw, Poland Email: Sara Cheek - [email protected]; Krzysztof Ginalski - [email protected]; Hong Zhang - [email protected]; Nick V Grishin* - [email protected] * Corresponding author Published: 16 March 2005 Received: 11 January 2005 Accepted: 16 March 2005 BMC Structural Biology 2005, 5:6 doi:10.1186/1472-6807-5-6 This article is available from: http://www.biomedcentral.com/1472-6807/5/6 © 2005 Cheek et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: A comprehensive update of the classification of all available kinases was carried out. This survey presents a complete global picture of this large functional class of proteins and confirms the soundness of our initial kinase classification scheme. Results: The new survey found the total number of kinase sequences in the protein database has increased more than three-fold (from 17,310 to 59,402), and the number of determined kinase structures increased two-fold (from 359 to 702) in the past three years.