Title:
COMPOUNDS AND METHODS TO INHIBIT OR AUGMENT AN INFLAMMATORY RESPONSE
Document Type and Number:
WIPO Patent Application WO/2000/042071
Kind Code:
A2
Abstract:
Isolated and purified chemokine peptides, variants, and derivatives thereof, as well as chemokine peptide analogs, are provided.
Inventors:
GRAINGER DAVID J (GB)
TATALICK LAUREN MARIE (US)
Application Number:
PCT/US2000/000821
Publication Date:
July 20, 2000
Filing Date:
January 12, 2000
Assignee:
NEORX CORP (US)
GRAINGER DAVID J (GB)
TATALICK LAUREN MARIE (US)
International Classes:
G01N33/50; A61K31/198; A61K31/4015; A61K31/437; A61K31/4375; A61K31/45; A61K31/472; A61K31/4745; A61K31/475; A61K31/513; A61K31/515; A61K31/7052; A61K38/00; A61K47/48; A61P9/00; A61P9/10; A61P11/06; A61P17/02; A61P17/06; A61P19/10; A61P29/00; A61P31/12; A61P31/18; A61P33/00; A61P35/00; A61P37/02; A61P37/06; A61P37/08; A61P43/00; C07D207/416; C07D211/88; C07D217/24; C07D457/04; C07D457/06; C07D459/00; C07D471/04; C07K5/08; C07K5/097; C07K14/52; G01N33/15; (IPC1-7): C07K14/52; A61K31/435; A61K38/19; C07C229/30; C07C237/22; C07D209/48; C07D457/00; C07D459/00
Domestic Patent References:
| WO1999012968A2 | 1999-03-18 | | | |
| WO1986004334A1 | 1986-07-31 | | | |
| WO1995005191A1 | 1995-02-23 | | | |
| WO1998042354A1 | 1998-10-01 | | | |
| WO1993010796A1 | 1993-06-10 | | | |
| WO1996029074A1 | 1996-09-26 | | | |
Foreign References:
| US5459128A | 1995-10-17 | | | |
| US5824647A | 1998-10-20 | | | |
| US5807482A | 1998-09-15 | | | |
| US5028594A | 1991-07-02 | | | |
| DE2710246A1 | 1977-09-22 | | | |
Other References:
YOSHIHIRO SHIBBATA ET AL.: "N-Alkylphtalimides: Sructural Requirement of Thalidomidal Action on 12-O-Tetradecanoylphorbol- 13- acetate Induced Tumor Necrosis Factor alpha Production by Human Leukemia HL-60 Cells" CHEM.PHARM.BULL., vol. 43, no. 1, 1995, pages 177-9, XP002146324
See also references of EP 1141011A2
Attorney, Agent or Firm:
Viksnins, Ann S. (Lundberg Woessner & Kluth P.O. Box 2938 Minneapolis, MN, US)
Claims:
| 1. |
A method of preventing or inhibiting an indication associated with a chemokineinduced activity, comprising: administering to a mammal afflicted with, or at risk of, the indication an amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof; effective to prevent or inhibit said activity, wherein the chemokine is not IL8 or NAP2. |
| 2. |
A method to inhibit the activity of more than one chemokine, comprising: administering to a mammal in need thereof an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof; or a combination thereof. |
| 3. |
A method of preventing or inhibiting an indication associated with hematopoietic cell recruitment, comprising: administering to a mammal at risk of, or afflicted with, the indication an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 4. |
A method of preventing or inhibiting an indication associated with histamine release from basophils or mast cells, comprising administering to a mammal at risk of, or afflicted with, the indication an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 5. |
A method to modulate the chemokineinduced activity of hematopoietic cells at a preselected physiological site, comprising: administering to a mammal a dosage form comprising an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof ; wherein the dosage form is linked to a site targeting moiety. |
| 6. |
A method to prevent or inhibit stroke, comprising: administering to a mammal an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of, chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 7. |
A therapeutic method to prevent or treat a vascular indication, comprising: administering to a mammal in need of such therapy an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof ; wherein the indication is coronary artery disease, myocardial infarction, unstable angina pectoris, atherosclerosis or vasculitis. |
| 8. |
A therapeutic method to prevent or treat low bone mineral density, comprising: administering to a mammal in need of such therapy an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 9. |
A therapeutic method to prevent or treat an autoimmune disease, comprising: administering to a mammal in need of such therapy an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); or 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), or a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof; or a combination thereof. |
| 10. |
A method of suppressing tumor growth in a vertebrate animal, comprising: administering to said vertebrate an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 11. |
A method for preventing or treating psoriasis in a mammal, comprising: administering to the mammal an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 12. |
A method to enhance wound healing, comprising: administering an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 13. |
A method of treating a mammal afflicted with, or at risk of, an indication associated with chemokineinduced activity, comprising: administering to the mammal an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof; or a combination thereof. |
| 14. |
A therapeutic method to prevent or treat asthma, comprising: administering to a mammal in need of such therapy an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 15. |
The method of claim 1 wherein the amount inhibits a product or intermediate in the arachidonic acid pathway. |
| 16. |
The method of claim 15 wherein leukotriene is inhibited. |
| 17. |
The method of claim 15 wherein thromboxane is inhibited. |
| 18. |
The method of claim 15 wherein prostaglandin is inhibited. |
| 19. |
A method of preventing or inhibiting an indication associated with elevated TNFa, comprising: administering to a mammal afflicted with, or at risk of, the indication an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof; or a combination thereof. |
| 20. |
A therapeutic method to prevent or treat organ transplant rejection, comprising: administering to a mammal in need of such therapy an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 21. |
A therapeutic method to prevent or treat rheumatoid arthritis, comprising: administering to a mammal in need of such therapy an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 22. |
A therapeutic method to prevent or treat allergy, comprising: administering to a mammal in need of such therapy an effective amount of : 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof; or a combination thereof. |
| 23. |
A compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a pharmaceutically acceptable salt thereof, that binds to the Duffy antigen of red blood cells with a decreased affinity relative to the corresponding chemokine. |
| 24. |
A compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a pharmaceutically acceptable salt thereof. |
| 25. |
A saccharide conjugate of: a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof. |
| 26. |
A compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a pharmaceutically acceptable salt thereof, that binds to the Duffy antigen of red blood cells with a decreased affinity relative to the corresponding chemokine peptide or chemokine. |
| 27. |
The saccharide conjugate of claim 25 wherein the compound binds to the Duffy antigen of red blood cells with a decreased affinity relative to the corresponding chemokine peptide or chemokine. |
| 28. |
A method to identify an agent that inhibits antigeninduced recall response, comprising: a) administering to a mammal which is sensitized to an antigen an agent selected from 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); and 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), or a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof; or a combination thereof; and b) detecting or determining whether the agent inhibits the recall response. |
| 29. |
A method of preventing or inhibiting a recall response to an antigen, comprising: administering to a mammal which is sensitized to the antigen an amount of an agent effective to inhibit or decrease IL4 levels in the mammal; wherein the agent is selected from: 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); and 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 30. |
A method of preventing or inhibiting a recall response to an antigen, comprising: administering to a mammal which is sensitized to the antigen an amount of an agent effective to inhibit or decrease immunoglobulin levels in the mammal; wherein the agent is selected from: 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII); and 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), or a compound of formula (XIX); or a pharmaceutically acceptable salt thereof; or a combination thereof. |
| 31. |
A method of suppressing the immune response of a mammal subjected to a therapy which employs an immunogenic therapeutic molecule, comprising: administering to the mammal an amount of an agent effective to inhibit antigeninduced recall response to the immunogenic therapeutic molecule; wherein the agent is selected from: 1) a compound of formula (XIII), (XIV), (X), (XI), (XIX), and (XII); and 2) a saccharide conjugate of a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), and a compound of formula (XIX); or a pharmaceutically acceptable salt thereof ; or a combination thereof. |
| 32. |
A method to increase the in vivo halflife of compound selected from a chemokine peptide 3, a variant thereof, a derivative thereof, a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (XIII), a compound of formula (XIV), a compound of formula (X), a compound of formula (XI), a compound of formula (XII), and a compound of formula (XIX) comprising linking a saccharide to the compound. |
| 33. |
The saccharide linked compound of claim 33. |
| 34. |
A method to increase or enhance a chemokineassociated inflammatory response in a mammal, comprising: administering to the mammal an amount of a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a combination thereof effective to increase or enhance said response. |
| 35. |
A method to augment an immune response, comprising: administering to a mammal an immunogenic moiety and an amount of a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a combination thereof, wherein the amount is effective to augment the immune response of the mammal to the immunogenic moiety. |
| 36. |
A therapeutic method to prevent or inhibit lentiviral infection or replication, comprising: administering to a mammal in need of such therapy an effective amount of a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a combination thereof. |
| 37. |
The method of claim 36 wherein the lentivirus is HIV. |
| 38. |
The method of claim 37 further comprising administering an antiviral agent before, during and/or after the administration of the compound or a combination. |
| 39. |
A method of inhibiting a parasitic infection in a vertebrate animal, comprising: administering to the animal an effective amount of a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a combination thereof. |
| 40. |
The method of claim 39 wherein the animal is a human with malaria. |
| 41. |
A method to increase or enhance hematopoietic cellassociated activity at a tumor site, comprising: administering an effective amount of a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a combination thereof. |
| 42. |
An immunogenic composition comprising an immunogenic moiety and an amount of a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a combination thereof. |
| 43. |
Use of a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), or a combination thereof for the manufacture of a medicament for the treatment of a pathological condition or symptom in a mammal which is associated with a chemokineinduced activity. |
| 44. |
A pharmaceutical composition comprising a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), which binds to the Duffy antigen on red blood cells and a pharmaceutically acceptable carrier. |
| 45. |
The pharmaceutical composition of claim 44 wherein compound is associated with a biologically active molecule. |
| 46. |
The pharmaceutical composition of claim 45 wherein the biologically active molecule is a peptide, polypeptide or protein. |
| 47. |
The pharmaceutical composition of claim 46 wherein the biologically active molecule is human growth hormone or insulin. |
| 48. |
The pharmaceutical composition of claim 45 wherein the biologically active molecule is immunogenic. |
| 49. |
The pharmaceutical composition of claim 45 wherein the biologically active molecule when it is not associated with the compound is rapidly cleared from the circulation. |
| 50. |
The pharmaceutical composition of claim 45 wherein the compound and the biologically active molecule are covalently bonded. |
| 51. |
The pharmaceutical composition of claim 45 wherein the compound is associated with a detectable molecule. |
| 52. |
A method to modulate the pharmacokinetics of a biologically active molecule, comprising: associating a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), which binds to the Duffy antigen on red blood cells with the biologically active molecule, wherein the pharmacokinetic properties of the associated biologically active molecule are different than the pharmacokinetic properties of the biologically active molecule alone. |
| 53. |
A method to alter the pharmacokinetics of a biologically active molecule in a mammal, comprising: administering to the mammal the biologically active molecule in association with a compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII), which binds to the Duffy antigen on red blood cells. |
| 54. |
A compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII) that binds to the Duffy antigen of red blood cells with a decreased affinity relative to the corresponding chemokine. |
| 55. |
A compound of formula (XIII), (XIV), (X), (XI), (XIX), or (XII) that binds to the Duffy antigen of red blood cells with a decreased affinity relative to the corresponding chemokine peptide or chemokine. |
| 56. |
A moiety that binds to the Duffy antigen of red blood cells with at least about a tenfold reduced affinity for the Duffy antigen relative to the binding of moiety to at least one chemokine receptor. |
| 57. |
A moiety that binds to the Duffy antigen of red blood cells with at least about a tenfold increased affinity for the Duffy antigen relative to the binding of the moiety to at least one chemokine receptor. |
| 58. |
A method to identify a region of a chemokine receptor which binds to a chemokine peptide, a variant, derivative or analog thereof comprising: (a) contacting a chemokine receptor with an amount of the chemokine peptide, a variant, derivative or analog thereof so as to result in a complex between the receptor and the chemokine peptide, a variant, derivative or analog thereof ; and (b) determining which region of the receptor is bound to the chemokine peptide, variant, derivative or analog thereof. |
| 59. |
A method to identify a molecule which binds to a region of a chemokine receptor that is bound by a specific chemokine peptide, a variant, derivative or analog thereof, comprising: (a) contacting the region with a population of molecules; and (b) detecting or determining whether at least one molecule of the population of molecules specifically binds to the region. |
| 60. |
A method to identify a molecule that binds to a chemokine receptor but which molecule does not form a heterodimer with at least one chemokine that binds to the receptor, comprising: (a) contacting the chemokine receptor with the molecule so as to form a complex between the receptor and the molecule; (b) contacting the complex with at least one chemokine; and (c) detecting or determining whether the molecule in the complex forms a heterodimer with the chemokine. |
| 61. |
A method to identify a molecule that binds to a chemokine receptor but which molecule does not form a heterodimer with a chemokine that binds to the receptor, comprising: (a) contacting the chemokine receptor with the molecule and at least one chemokine; and (b) detecting or determining whether the molecule forms a heterodimer with the chemokine. |
| 62. |
A method to identify an agent which inhibits chemokine activity but does not compete with native chemokine for its receptor, comprising: (a) contacting cells with the agent, wherein the cells comprise receptors that bind native chemokine; and (b) detecting or determining whether the agent specifically binds to a receptor which is not the receptor which binds native chemokine and inhibits chemokine activity. |
Description:
INTERNATIONAL SEARCH REPORT lntt ional Application No PCT/US 00/00821 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. X WO 95 05191 A (UAB RESEARCH FOUNDATION) 1-22 23 February 1995 (1995-02-23) claims 1-21; tables I-III X US 5 807 482 A (HOUSE DAVID W) 23,24, 15 September 1998 (1998-09-15) 26,44-49 column 5, line 1-line 28 X WO 98 42354 A (UNIV MARYLAND BIOTECHNOLOGY 1,36-38, IN) 1 October 1998 (1998-10-01) 58-62 claims1,6,31 Y WO 93 10796 A (GLYCOMED INC) 25,27 10 June 1993 (1993-06-10) claim 15 Y US 5 028 594 A (CARSON DENNIS A) 25,27 2 July 1991 (1991-07-02) claim1 X WO 96 29074 A (LILLY CO ELI) 23,24, 26 September 1996 (1996-09-26) 26,44-49 page 13, line 7-line 10 X DE 27 10 246 A (RICHTER GEDEON VEGYESZET) 23. 24, 22 September 1977 (1977-09-22) 26. 44-49 claim1 X YOSHIHIRO SHIBBATA ET AL. : 23,24, "N-Alkylphtalimides : Sructural Requirement 26,44-49 of Thalidomidal Action on 12-0-Tetradecanoylphorbol-13-acetate Induced Tumor Necrosis Factor alpha Production by Human Leukemia HL-60 Cells" CHEM. PHARM. BULL., vol. 43, no. 1, 1995, pages 177-9, XP002146324 examples 4, 5, 7 ; table I vint., ational application No. INTERNATIONAL SEARCH REPORT PCT/US 00/00821 Box I Observations where certain claims were found unsearchable (Continuation of item 1 of first sheet) This International Search Report has not been established in respect of certain claims under Article 17 (2) (a) for the following reasons: 1. Nos. : because they relate to subject matter not required to be searched by this Authority, namely: Although claims 1-14,19-22,29-32,34-36,52,53 are directed to a method of treatment of the human/animal body, the partial search has been carried out and based on the alleged effects of the compound/composition. 2. Claims Nos. : 1-62 (partially) because they relate to parts of the International Application that do not comply with the prescribed requirements to such an extent that no meaningful International Search can be carried out, specifically : see FURTHER INFORMATION sheet PCT/ISA/210 3 Claims Nos.: because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6. 4 (a). Box 11 Observations where unity of invention is lacking (Continuation of item 2 of first sheet) This International Searching Authority found multiple inventions in this international application, as follows: 1 As all required additional search fees were timely paid by the applicant, this International Search Report covers all searchable claims. 2. As ai ! searchable claims could be searched without effort justifying an additional fee, this Authority did not invite payment of any additional fee. 3. As on ! y some of the required additional search fees were timely paid by the applicant, this International Search Report covers only those claims for which fees were paid, specifically claims Nos.: 4. nj No required additional search fees were timely paid by the applicant. Consequently, this International Search Report is restricted to the invention first mentioned in the claims ; it is covered by claims : Remark on Protest The additional search fees were accompanied by the applicant's protest. u n No protest accompanied the payment of additional search fees LJ FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 Continuation of Box 1. 2 Claims Nos.: 1-62 (partially) Present claims 1-62 relate to an extremely large number of possible compounds and methods. Support within the meaning of Article 6 PCT and disclosure within the meaning of Article 5 PCT is to be found, however, for only a very small proportion of the compounds and methods claimed. In the present case, the claims so lack support, and the application so lacks disclosure, that a meaningful search over the whole of the claimed scope is impossible. Consequently, the search has been carried out for those parts of the claims which appear to be supported and disclosed, namely those parts relating to the compounds and methods exemplified in examples 1 to 7 of the present application. In addition Claims 1 to 14,19 to 22,29 to 32 to 36,52,53 have been drafted as separated independent claims directed to different uses of known and unknown compounds taking reference to the description. However, reading the description the application is directed to different compounds itself comprising different formulae I to XIX. This renders the scope of the claims unclear because the application might also be directed to the compounds I to XiX istelf. Lack of clarity of the claims as a whole arises, since the plurality of independent claims makes it difficult, if not impossible, to determine the matter for which protection is sought, and places an undue burden on others seeking to establish the extent of the protection (Article 6 PCT). The definition of'chemokine peptide 3'in combination with the terms 'variant or derivative thereof'in the claims is vague and unclear. The definitions given in the description according to formula I to XIX contain so many options, variables, possible permutations and provisos that a lack of clarity within the meaning of Article 6 PCT arises to such an extent as to render a meaningful search of the claims impossible. In addition claims 1 to 14 for example comprise saccharide conjugate of a chemokine peptide 3, a variant thereof and different compounds of different formula. It is not clear wether use of the saccharide conjugate of peptide 3 only or also of all other formulae is claimed. Article 17 (2) (a) (ii) and (b) PCT, Guidelines CIII, 2.1 and CIII, 3.7 Consequently, the search has been carried out for those parts of the application which do appear to be clear namely 1-62 partially in as far as compounds and tests of examples 1 to 28 and those specifically listed on pages 51 to 54 are concerned. The applicant's attention is drawn to the fact that claims, or parts of claims, relating to inventions in respect of which no international search report has been established need not be the subject of an international preliminary examination (Rule 66.1 (e) PCT). The applicant is advised that the EPO policy when acting as an International Preliminary Examining Authority is normally not to carry out a preliminary examination on matter which has not been searched. This is FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 the case irrespective of whether or not the claims are amended following receipt of the search report or during any Chapter II 0 INTERNATIONAL SEARCH REPORT lnte ional Application No Information on patent family members PCT/US 00/00821 PCT/US 00/00821 Patent document Publication Patent cited in search report date member (s) date WO 9912968 A 18-03-1999 AU 9315398 A 29-03-1999 EP 1012187 A 28-06-2000 US 5459128 A 17-10-1995 Us 5739103 A 14-04-1998 Us 5705360 A 06-01-1998 Us 5854412 A 29-12-1998 EP 0725794 A 14-08-1996 JP 9505053 T 20-05-1997 WO 9513295 A 18-05-1995 US 5824647 A 20-10-1998 Us 5436228 A 25-07-1995 WO 8604334 A 31-07-1986 AU 602483 B 18-10-1990 AU 5319886 A 13-08-1986 EP 0215805 A 01-04-1987 JP 62501502 T 18-06-1987 WO 9505191 A 23-02-1995 AU 697624 B 15-10-1998 AU 7565294 A 14-03-1995 CA 2169360 A 23-02-1995 EP 0716609 A 19-06-1996 JP 9505555 T 03-06-1997 US 5807482 A 15-09-1998 NONE WO 9842354 A 01-10-1998 AU6587598 A20-10-1998 ____________________________________________________________
___________ WO 9310796 A 10-06-1993 US 5326752 A 05-07-1994 AU 3138493 A 28-06-1993 EP 0614367 A 14-09-1994 JP 7501341 T 09-02-1995 Us 5567683 A 22-10-1996 US 5028594 A 02-07-1991 NONE WO 9629074 A 26-09-1996 AU 5528996 A 08-10-1996 DE 2710246 A 22-09-1977 HU 172479 B 28-09-1978 AT 357693 B 25-07-1980 AT 145077 A 15-12-1979 CA 1099261 A 14-04-1981 DK 100477 A 10-09-1977 FR 2343744 A 07-10-1977 GB 1557419 A 12-12-1979 GR 62474 A 13-04-1979 JP 52122399 A 14-10-1977 NL 7702545 A 13-09-1977 SE 7702260 A 10-09-1977 Us 4108855 A 22-08-1978
