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  Immunoregulatory compositionsUSPTO Application #: 20080076719Title: Immunoregulatory compositions Abstract: The invention relates to compounds exhibiting immunoregulatory activity as determined by measuring the compound's ability to modulate production of NO by a cell. Preferred compounds include or consist of a sequence AAL AAQ AAG AAV wherein AAL is a substituted or unsubstituted non-polar amino acid selected from the group consisting of Ala and Leu; wherein AAQ is a substituted or unsubstituted amino acid selected from the group consisting of Gln, Pro, and Ala; wherein AAG is a substituted or unsubstituted amino acid Gly, and wherein AAV is a substituted or unsubstituted non-polar amino acid selected from the group consisting of Val and Ala. In one embodiment, the compound consists of a tripeptide selected from the group AQG, MTR, VVC, and mixtures thereof. (end of abstract)
Agent: - , USPTO Applicaton #: 20080076719 - Class: 514016000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 7 Or 8 Peptide Repeating Units In Known Peptide Chain The Patent Description & Claims data below is from USPTO Patent Application 20080076719. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of application Ser. No. 10/753,510, filed Jan. 7, 2004, pending, which is a continuation in part of U.S. Ser. No. 10/028,075, filed Dec. 21, 2001, a continuation of U.S. Ser. No. 10/262,522, filed Sep. 30, 2002, which is a continuation of International Application No. PCT/NL01/00259, designating the United States of America published in English as PCT International Publication No. WO 01/72831 A2 filed Mar. 3, 2001; and application Ser. No. 10/753,510 is further a continuation in pan of International Application No. PCT/NL02/00639, designating the United States of America and published on Apr. 10, 2003 in English as PCT International Publication No. WO 03/029292 A2. The disclosure of each of the herein referenced U.S. patents, U.S. patent applications and PCT patent publications is hereby incorporated herein by reference in its entirety. TECHNICAL FIELD [0002] The invention relates generally to biotechnology, and more specifically to compositions having immunoregulatory activity, which compounds include particular oligopeptides derived from human chorionic gonadotropiin (hCG). BACKGROUND [0003] U.S. Pat. No. 5,380,668 to Herron (Jan. 10, 1995), the contents of the entirety of which are incorporated by this reference, discloses, among other things, various compounds having the antigenic binding activity of hCG. The oligopeptides disclosed therein are disclosed generally for use in diagnostic methods. [0004] Various patents and patent applications to Gallo et al. (e.g., U.S. Pat. No. 5,677,275 (corresponding to WO 96/04008 A1), U.S. Pat. No. 5,877,148 (also corresponding to WO 96/04008 A1), WO 97/49721 A1, U.S. Pat. No. 6,319,504 (corresponding to WO 97/49373), U.S. Patent Application 2003/0049273 A1 (also corresponding to WO 97/49373), U.S. Pat. No. 5,968,513 (corresponding to WO 97/49418), U.S. Pat. No. 5,997,871 (corresponding to WO 97/49432), U.S. Pat. No. 6,620,416, U.S. Pat. No. 6,596,688, WO 01/1148 A2, WO 01/10907 A2, and U.S. Pat. No. 6,583,109) relate to various oligopeptides and their use in, among other things, "inhibiting HIV infection," "treating or preventing HIV infection," "treating or preventing cancer," "treating or preventing a condition characterized by loss of body cell mass," "treating or preventing a condition associated with pathological angiogenesis," "treating or preventing hematopoietic deficiency," "ex vivo gene therapy," "expanding blood cells in vitro," and/or "providing blood cells to a subject". DISCLOSURE OF THE INVENTION [0005] As we described in PCT International Publication No. WO 03/029292 A2 (published Apr. 10, 2003), PCT International Publication No. WO 01/72831 A2 (published Oct. 4, 2001), and U.S. Patent Application Publications 20020064501 A1 (published May 30, 2002), 20030119720 A1 (published Jun. 26, 2003), 20030113733 A1 (published Jun. 19, 2003), and 20030166556 A1 (published Sep. 4, 2003), the contents of all of which are incorporated by this reference, compositions containing purified or isolated oligopeptides described herein have immunoregulatory activity useful in, for example, the treatment of sepsis and other disease states and conditions. They also have gene regulatory activities. [0006] The invention thus includes a composition comprising a purified or isolated peptide consisting of particular four to eight amino acid segments of the sequence MTRVLQGVLPALPQVVC (SEQ ID NO:44 of the incorporated herein SEQUENCE LISTING); and derivatives thereof having one or more conservative substitutions relative to the sequence of SEQ ID NO:44. The particular compositions exhibit immunoregulatory activity as determined by measuring the segment's ability to modulate production of NO by a cell. Preferably, the compositions have the ability to decrease shock in a subject (e.g., a mammal) undergoing sepsis. [0007] In one embodiment, the amino acid segment includes a tetrameric sequence (corresponding to the LQVG (SEQ ID NO:1) portion of SEQ ID NO:44, i.e., [0008] AAL AAQ AAG AAV [0009] wherein AAL is a substituted or unsubstituted non-polar amino acid selected from the group consisting of Ala and Leu; AAQ is a substituted or unsubstituted amino acid selected from the group consisting of Gln, Pro, and Ala; AAG is a substituted or unsubstituted Gly; and AAV is a substituted or unsubstituted non-polar amino acid selected from the group consisting of Val and Ala. For instance, the peptide could be selected from the group consisting of LQGV (SEQ ID NO:1), the derivative AQGV (SEQ ID NO:2), the derivative LQGA (SEQ ID NO:19), the derivative LAGV (SEQ ID NO:26), and the derivativeLPGC (SEQ ID NO:41). [0010] In a different embodiment, the segment is the tetramer MTRV (SEQ ID NO:42) or QVVC (SEQ ID NO:43). [0011] In another embodiment, the segment is six or seven amino acids long, and comprises the sequence [0012] AAV AAL Pro Arg AAL2 AAP wherein AAV is substituted or unsubstituted Val or Ala, wherein AAL and AAL2 are independently selected from substituted or unsubstituted Lys or Ala, and wherein AAP is a substituted or unsubstituted Pro or Ala. [0013] In such an embodiment, the purified or isolated peptide can have a formula selected from the group consisting of VLPALP (SEQ ID NO:3), the derivative ALPALP (SEQ ID NO:21), the derivative VAPALP (SEQ ID NO:22), the derivative ALPALPQ (SEQ ID NO:23), the derivative VLPAAPQ (SEQ ID NO:24), the derivative VLPALAQ (SEQ ID NO:25), the derivative VLPALA (SEQ ID NO:28), VLPALPQ (SEQ ID NO:29), the derivative VLPALPA (SEQ ID NO:31), the derivative GVLPALP (SEQ ID NO:32), and the derivative VLAALP (SEQ ID NO:117). [0014] In another embodiment, the composition has no more than eight amino acids, and includes an amino acid sequence consisting of: [0015] AAL AAQ AAG AAV wherein AAL is a substituted or unsubstituted amino acid selected from the group of amino acids consisting of Ala, Leu, and Met, wherein AAQ is a substituted or unsubstituted amino acid selected from the group of amino acids consisting of Gln, Thr, Ala, and Pro, wherein AAG is substituted or unsubstituted Gly or Arg, and wherein AAV is a substituted or unsubstituted amino acid selected from the group of amino acids consisting of Cys, Ala, and Val. Again such a composition is characterized in having immunoregulatory activity as determined by: measuring its capability of modulating production of NO by a cell. [0016] In such an embodiment, the sequence is preferably selected from the group consisting of Leu Gln Gly Val (SEQ ID NO: 1), Ala Gln Gly Val (SEQ ID NO:2), Leu Gln Gly Ala (SEQ ID NO:19), Leu Ala Gly Val (SEQ ID NO:26), Leu Pro Gly Cys (SEQ ID NO:41), and Met Thr Arg Val (SEQ ID NO:42). Preferably, the composition is the sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:19, SEQ ID NO:26, SEQ ID NO:41, SEQ ID NO:42, or a salt of any thereof. [0017] The invention further includes a pharmaceutical composition comprising a purified or isolated peptide, or acid addition salt thereof, the purified or isolated peptide (a) consisting of an amino acid sequence selected from the group consisting of: (i) a four to seven amino acid segment of the sequence of MTRVLQGVLPALPQVVC (SEQ ID NO:44); and (ii) a derivative of the segment of (a) having one or more conservative substitutions relative to the sequence of SEQ ID NO:44; and (b) exhibiting an immunoregulatory activity as determined by measuring its capability of modulating production of NO by a cell. [0018] Such a pharmaceutical composition preferably includes a sequence selected from the group selected from the group consisting of LQGV (SEQ ID NO:1), AQGV (SEQ ID NO:2), VLPALP (SEQ ID NO:3), LQGA (SEQ ID NO:19), ALPALP (SEQ ID NO:21), VAPALP (SEQ ID NO:22), ALPALPQ (SEQ ID NO:23), VLPAAPQ (SEQ ID NO:24), VLPALAQ (SEQ ID NO:25), LAGV (SEQ ID NO:26), VLPALA (SEQ ID NO:28), VLPALPQ (SEQ ID NO:29), VLPALPA (SEQ ID NO:31), and GVLPALP (SEQ ID NO:32), LPGC (SEQ ID NO:41), MTRV (SEQ ID NO:42), QVVC (SEQ ID NO:43), VLAALP (SEQ ID NO:117), and combinations of any thereof, with or without other active or inactive ingredients, presented in a pharmaceutically acceptable form for administration to a human. [0019] In one preferred embodiment, the invention is a purified or isolated peptide consisting of GVLPALPQ (SEQ ID NO:33), or an acid addition salt thereof. The invention would thus also include a pharmaceutical composition comprising the peptide of SEQ ID NO:33 or an addition salt thereof, together with a pharmaceutically acceptable excipient. [0020] In another embodiment the invention comprises a purified or isolated peptide (or, for example, acid addition salt thereof), selected from the group consisting of AQG. MTR, and VVC. [0021] Finally the invention includes a composition comprising one or more of the following amino acid segments: LQGV (SEQ ID NO:1), AQGV (SEQ ID NO:2), VLPALP (SEQ ID NO:3), LQGA (SEQ ID NO:19), ALPALP (SEQ ID NO:21), VAPALP (SEQ ID NO:22), ALPALPQ (SEQ ID NO:23), VLPAAPQ (SEQ ID NO:24), VLPALAQ (SEQ ID NO:25), LAGV (SEQ ID NO:26), VLPALA (SEQ ID NO:28), VLPALPQ (SEQ ID NO:29), VLPALPA (SEQ ID NO:31), and GVLPALP (SEQ ID NO:32), LPGC (SEQ ID NO:41), MTRV (SEQ ID NO:42), QVVC (SEQ ID NO:43), VLAALP (SEQ ID NO:117), AQG, MTR, or VVC. [0022] In another embodiment, the invention includes a composition comprising a purified or isolated peptide consisting of sequence LQG in an amount sufficient to exhibit an immunoregulatory activity as determined by measuring the sequence LQG's ability to modulate production of NO by a cell. [0023] The invention provides a method for the treatment of bone disease such as osteoporosis comprising administering to a subject believed to be in need of such treatment a composition comprising an oligopeptide, derivative or functional analogue thereof, the particular molecule capable of modulating production of NO and/or TNF-alpha by a cell. Continue reading... Full patent description for Immunoregulatory compositions Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Immunoregulatory compositions patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. 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