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Uses of humans zven proteins and polynucleotidesRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Lymphokine, InterleukinUses of humans zven proteins and polynucleotides description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070065404, Uses of humans zven proteins and polynucleotides. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of U.S. application Ser. No. 10/680,800, filed Oct. 7, 2003, which claims the benefit of U.S. Provisional Application Ser. No. 60/416,719, filed Oct. 7, 2002; U.S. Provisional Application Ser. No. 60/416,718, filed Oct. 7, 2002; U.S. Provisional Application Ser. No. 60/434,116, filed Dec. 16, 2002; U.S. Provisional Application Ser. No. 60/433,918, filed Dec. 16, 2002; U.S. Provisional Application Ser. No. 60/508,614, filed Oct. 3, 2003; and U.S. Provisional Application Ser. No. 60/508,603, filed Oct. 3, 2003, all of which are herein incorporated by reference. BACKGROUND OF THE INVENTION [0002] Optimal gastrointestinal function includes mixing and forward propulsion of contents in the stomach and intestine. Gastric emptying is frequently abnormal in patients with critical illness or who are recovering from surgery. Recovery of gastrointestinal function and resumption of oral intake are important determinants in recovery from an event that compromises gastrointestinal function. Several events can lead to dysfunction in the gastrointestinal system, including, for example, ileus (post-operative and paralytic), chronic constipation, gastroparesis (including diabetic gastroparesis), intestinal pseudo-obstruction, dyspepsia, gastroesophageal reflux, and emesis. [0003] Diseases and disorders of impaired or compromised gastrointestinal function include ileus and gastroparesis. Post-operative ileus (POI) is a condition of reduced intestinal tract motility, including delayed gastric emptying, that occurs as a result of disrupted muscle tone following surgery. It is especially problematic following abdominal surgery. The problem may arise from the surgery itself, from the residual effects of anesthetic agents, and particularly, from pain-relieving narcotic and opiate drugs used during and after surgery. Post-operative ileus can be categorized as "uncomplicated", lasting two to three days after surgery, or as "paralytic", lasting more than three days after surgery. Thus, patients undergoing abdominal surgery who have a delay in recovery of gastrointestinal function have prolonged hospital stays, which can lead to increased medical costs and potentially to other complications. An estimated 750 million to one billion dollars is spent each year in increased hospitalization due to post-operative ileus. Currently there are no drugs that have been approved for treatment of this disease. [0004] In addition to the need for a better therapeutic for post-operative ileus, there is a need for a better therapeutic for diabetic gastroparesis. Diabetic gastroparesis is paralysis of the stomach brought about by a motor abnormality in the stomach, as a complication of both type I and type II diabetes. Diabetic gastroparesis is characterized by delayed gastric emptying, post-prandial distention, nausea and vomiting. In diabetes, it is thought to be due to a neuropathy, though it is also associated with loss of interstitial cells of Cajal (ICC), which are the "pacemaker cells" of the gut. [0005] In the U.S. alone, there are at least 16 million individuals with diabetes, affecting approximately 7% of the population. The prevalence is continuing to increase and is growing worldwide. Since up to two-thirds of individuals with diabetes suffer from some degree of gastroparesis, this problem is significant. Episodes are often acute, though long-term treatment is often required. Moreover, symptoms associated with diabetic gastroparesis, such as delayed gastric emptying, and emesis can cause water and electrolyte imbalances, poor glycemic control, and ensuing complications. If severe enough, it may require hospitalization for control of diabetes, and treatment with intravenous fluids and nutrition. [0006] The often-acute nature of the episodes provides an opportunity to treat with a prokinetic. Currently there are very few drugs that can effectively treat diabetic gastroparesis, and those that are available have side effects and/or cannot be taken with other medications. Oral drugs may not be tolerated during severe episodes, and thus, would require intravenous administration of a prokinetic. In the United States, only two agents, erythromycin and metoclopramide, are available to treat gastroparesis. [0007] Thus, a need still exists for therapeutic approaches to treatment of gastric function disorders. BRIEF SUMMARY OF THE INVENTION [0008] The present invention provides proteins useful for the treatment in recovery of gastronintestinal function and gastric emptying. Other uses of Zven1 and Zven2 polypeptides are described in more detail below. DESCRIPTION OF THE INVENTION 1. OVERVIEW [0009] The present invention is directed to novel uses of previously described proteins, Zven1 and Zven2. See U.S. patent application Ser. No. 09/712,529, now issued as U.S. Pat. No. 6,485,938. Zven1 and Zven2 are also known in the industry as Prokineticin2 and Prokineticin1, respectively. As discussed herein, Zven1 and Zven2, as well as variants and fragments thereof, can be used to regulate gastrointestinal function and gastric emptying. Receptors for Zven1 (Prokineticin2) and Zven2 (Prokineticin1) have been identified as G protein-coupled receptors, GPCR73a and GPCR73b. See Lin, D. et al., J. Biol. Chem. 277: 19276-19280, 2002. The GPCR73a and GPCR73b receptors are also known as PK-R1 and PK-R2. [0010] The present invention provides methods of using human Zven polypeptides and nucleic acid molecules that encode human Zven polypeptides. An illustrative nucleic acid molecule containing a sequence that encodes the Zven1 polypeptide has the nucleotide sequence of SEQ ID NO:1. The encoded polypeptide has the following amino acid sequence: MRSLCCAPLL LLLLLPPLLL TPRAGDAAVI TGACDKDSQC GGGMCCAVSI WVKSIRICTP MGKLGDSCHP LTRKVPFFGR RMHHTCPCLP GLACLRTSFN RFICLAQK (SEQ ID NO:2). Thus, the Zven1 nucleotide sequence described herein encodes a polypeptide of 108 amino acids. The putative signal sequences of Zven1 polypeptide reside at amino acid residues 1 to 20, 1 to 21, and 1 to 22 of SEQ ID NO:2. The mature form of the polypeptide comprises the amino acid sequence from amino acid 28 to 108 as shown in SEQ ID NO:2. [0011] A longer form of the sequence as shown in SEQ ID NO:2 is included in the invention described herein. The longer form has the following amino acid sequence: MRSLCCAPLL LLLLLPPLLL TPRAGDAAVI TGACDKDSQC GGGMCCAVSI WVKSIRICTP MGKLGDSCHP LTRKNNFGNG RQERRKRKRS KRKKEVPFFG RRMHHTCPCL PGLACLRTSF NRFICLAQK (SEQ ID NO:29). The putative signal sequence of the longer form has a mature form that comprises the amino acid sequence from amino acid 28 to 129 as shown in SEQ ID NO:29. [0012] An illustrative nucleic acid molecule containing a sequence that encodes the Zven2 polypeptide has the nucleotide sequence of SEQ ID NO:4. The encoded polypeptide has the following amino acid sequence: MRGATRVSIM LLLVTVSDCA VITGACERDV QCGAGTCCAI SLWLRGLRMC TPLGREGEEC HPGSHKVPFF RKRKHHTCPC LPNLLCSRFP DGRYRCSMDL KNINF (SEQ ID NO:5). Thus, the Zven2 nucleotide sequence described herein encodes a polypeptide of 105 amino acids. The putative signal sequences of Zven2 polypeptide reside at amino acid residues 1 to 17, and 1 to 19 of SEQ ID NO:5. [0013] As described below, the present invention provides isolated polypeptides comprising an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to amino acid residues 23 to 108 of SEQ ID NO:2, to amino acid residues 28 to 108 of SEQ ID NO:2, or to amino acid residues 28 to 129 if SEQ ID NO:29. Certain of such isolated polypeptides can specifically bind with an antibody that specifically binds with a polypeptide consisting of the amino acid sequence of SEQ ID NO:2. Particular polypeptides can increase or decrease gastric contractility, gastric emptying and/or intestinal transit. An illustrative polypeptide is a polypeptide that comprises the amino acid sequence of SEQ ID NO:2. [0014] Similarly, the present invention includes provides isolated polypeptides comprising an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to amino acid residues 20 to 105 of SEQ ID NO:5, wherein such isolated polypeptides can specifically bind with an antibody that specifically binds with a polypeptide consisting of the amino acid sequence of SEQ ID NO:5. An illustrative polypeptide is a polypeptide that comprises the amino acid sequence of SEQ ID NO:5. [0015] The present invention also provides polypeptides comprising an amino acid sequence selected from the group consisting of: (1) amino acid residues 21 to 108 of SEQ ID NO:2, (2) amino acid residues 22 to 108 of SEQ ID NO:2, (3) amino acid residues 23 to 108 of SEQ ID NO:2, (4) amino acid residues 82 to 108 of SEQ ID NO:2, (5) amino acid residues 1 to 78 (amide) of SEQ ID NO:2, (6) amino acid residues 1 to 79 of SEQ ID NO:2, (7) amino acid residues 21 to 78 (amide) of SEQ ID NO:2, (8) amino acid residues 21 to 79 of SEQ ID NO:2, (9) amino acid residues 22 to 78 (amide) of SEQ ID NO:2, (10) amino acid residues 22 to 79 of SEQ ID NO:2, (11) amino acid residues 23 to 78 (amide) of SEQ ID NO:2, (12) amino acid residues 23 to 79 of SEQ ID NO:2, (13) amino acid residues 20 to 108 of SEQ ID NO:2, (14) amino acid residues 20 to 72 of SEQ ID NO:2, (15) amino acid residues 20 to 79 of SEQ ID NO:2, (16) amino acid residues 20 to 79 (amide) of SEQ ID NO:2, (17) amino acid residues 21 to 72 of SEQ ID NO:2, (18) amino acid residues 21 to 79 (amide) of SEQ ID NO:2, (19) amino acid residues 22 to 72 of SEQ ID NO:2, (20) amino acid residues 22 to 79 (amide) of SEQ ID NO:2, (21) amino acid residues 23 to 72 of SEQ ID NO:2, (22) amino acid residues 23 to 79 (amide) of SEQ ID NO:2, (23) amino acid residues 28 to 108 of SEQ ID NO:2, (24) amino acid residues 28 to 72 of SEQ ID NO:2, (25) amino acid residues 28 to 79 of SEQ ID NO:2, (26) amino acid residues 28 to 79 (amide) of SEQ ID NO:2, (27) amino acid residues 75 to 108 of SEQ ID NO:2, (28) amino acid residues 75 to 79 of SEQ ID NO:2, and (29) amino acid residues 75 to 78 (amide) of SEQ ID NO:2. Illustrative polypeptides consist of amino acid sequences (1) to (29). The present invention also included polypeptide comprising an amino acid sequence comprising amino acid 28 to 129 as shown in SEQ ID NO:29, and/or fragments thereof. [0016] The present invention further includes polypeptides comprising an amino acid sequence selected from the group consisting of: (a) amino acid residues 20 to 105 of SEQ ID NO:5, (b) amino acid residues 18 to 105 of SEQ ID NO:5, (c) amino acid residues 1 to 70 of SEQ ID NO:5, (d) amino acid residues 20 to 70 of SEQ ID NO:5, (e) amino acid residues 18 to 70 of SEQ ID NO:5, (f) amino acid residues 76 to 105 of SEQ ID NO:5, (g) amino acid residues 66 to 105 of SEQ ID NO:5, and (h) amino acid residues 82 to 105 of SEQ ID NO:5. Illustrative polypeptides consist of amino acid sequences (a) to (h). [0017] The present invention further provides antibodies and antibody fragments that specifically bind with such polypeptides. Exemplary antibodies include polyclonal antibodies, murine monoclonal antibodies, humanized antibodies derived from murine monoclonal antibodies, and human monoclonal antibodies. Illustrative antibody fragments include F(ab').sub.2, F(ab).sub.2, Fab', Fab, Fv, scFv, and minimal recognition units. The present invention also includes anti-idiotype antibodies that specifically bind with such antibodies or antibody fragments. The present invention further includes compositions comprising a carrier and a peptide, polypeptide, antibody, or anti-idiotype antibody described herein. [0018] The present invention also provides isolated nucleic acid molecules that encode a Zven polypeptide, wherein the nucleic acid molecule is selected from the group consisting of (a) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:3, (b) a nucleic acid molecule encoding the amino acid sequence of SEQ ID NO:2, (c) a nucleic acid molecule that remains hybridized following stringent wash conditions to a nucleic acid molecule consisting of the nucleotide sequence of nucleotides 66 to 161 of SEQ ID NO:1, the nucleotide sequence of nucleotides 288 to 389 of SEQ ID NO:1, or to the complement of the nucleotide sequence of either nucleotides 66 to 161 of SEQ ID NO:1 or nucleotides 288 to 389 of SEQ ID NO:1, (d) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:6, (e) a nucleic acid molecule encoding the amino acid sequence of SEQ ID NO:5, (f) a nucleic acid molecule that remains hybridized following stringent wash conditions to a nucleic acid molecule consisting of the nucleotide sequence of nucleotides 334 to 405 of SEQ ID NO:4, or to the complement of the nucleotide sequence of nucleotides 334 to 405 of SEQ ID NO:4. [0019] Illustrative nucleic acid molecules include those in which any difference between the amino acid sequence encoded by the nucleic acid molecule and the corresponding amino acid sequence of either SEQ ID NO:2 or SEQ ID NO:5 is due to a conservative amino acid substitution. The present invention further contemplates isolated nucleic acid molecules that comprise a nucleotide sequence of nucleotides 132 to 389 of SEQ ID NO:1, nucleotides 147 to 389 of SEQ ID NO:1, and nucleotides 148 to 405 of SEQ ID NO:4. Continue reading about Uses of humans zven proteins and polynucleotides... Full patent description for Uses of humans zven proteins and polynucleotides Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Uses of humans zven proteins and polynucleotides patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. 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