Methods and compositions for inhibition of hepatic clearance of tissue-type plasminogen activator

• US 5,474,766 A
• Filed: 12/18/1992
• Issued: 12/12/1995
• Est. Priority Date: 12/18/1992
• Status: Expired due to Fees

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Bu, Guojun, Schwartz, Alan L.
• Primary Examiner(s): Allen, Marianne P.
• Application Number:
  US07/992,827
• Time in Patent Office: 1,089 Days
• Field of Search: 424/94.63, 424/94.64, 530/350, 530/395, 514/2, 514/12, 514/8
• US Class Current: 424/94.64
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748

Abstract

Methods and compositions for inhibiting the hepatic clearance of tissue-type plasminogen activator (t-PA) in vivo by administering a t-PA-hepatic clearance-inhibiting amount of 39 kDa protein or a t-PA-hepatic clearance-inhibiting fragment thereof, or genetically or chemically modified forms of the 39 kDa protein or fragments thereof are described. Methods and compositions for treatment of thrombolytic diseases by administering t-PA and a t-PA-hepatic clearance-inhibiting effective amount of 39 kDa protein, a t-PA-hepatic clearance inhibiting fragment thereof, and genetically or chemically modified forms of the 39 kDa protein or its fragments are described.

Claims

1. A 28 kDa protein having an amino acid sequence as set forth in SEQ ID NO:

2;

##STR4##

2. In a pharmaceutical composition for a mammalian patient containing tissue-type plasminogen activator (t-PA), the improvement comprising said composition further including a t-PA hepatic clearance-inhibiting amount of a protein selected from the group consisting of a 39 kDa protein having the amino acid sequence set forth in SEQ ID NO:

1and the 28 kDa protein of claim 1.

3. The pharmaceutical composition of claim 2, wherein the t-PA is present in a dosage amount of from about 0.15 to 1.5 mg/kg of body weight/dose.

4. The pharmaceutical composition of claim 2, wherein the 39 kDa protein is present in a dosage amount of from about 60 to 6,000 mg/kg of body weight/dose.

5. The pharmaceutical composition of claim 2, wherein the 28 kDa protein is present in a dosage amount of from about 38 to 3,800 mg/kg of body weight/dose.

6. A composition for treating thrombolytic diseases in a mammal comprising tissue-type plasminogen activator (t-PA) in an amount which is effective for treating said thrombolytic diseases, and a t-PA hepatic clearance-inhibiting protein selected from the group consisting of a 39 kDa protein having the amino acid sequence set forth in SEQ ID NO:

1 and the 28 kDa protein of claim 1 in an amount which is effective for inhibiting hepatic clearance of t-PA.

7. The composition of claim 6, wherein the t-PA is present in a dosage amount of from about 0.15 to 1.5 mg/kg of body weight/dose.

8. The composition of claim 6, wherein the 39 kDa protein thereof is present in a dosage amount of from about 60 to 6,000 mg/kg of body weight/dose.

9. The composition of claim 6, wherein the 28 kDa protein is present in a dosage amount of from about 38 to 3,800 mg/kg of body weight/dose.