Claims for Patent: 5,656,722

Summary for Patent: 5,656,722

Title:	A.sup.21 -, B.sup.30 - modified insulin derivatives having an altered action profile
Abstract:	New insulin derivatives, the use thereof, and a pharmaceutical composition containing them Insulin derivatives having an isoelectric point between 5 and 8.5, or physiologically tolerated salts thereof, of the Formula II ##STR1## in which: R.sup.1 at position B1 denotes H or H-Phe; R.sup.2 at position A21 denotes a genetically encodable L-amino acid selected from the group consisting of Gly, Ala, Val, Leu, Ile, Pro, Phe, Trp, Met, Ser, Thr, Cys, Tyr, Asp, and Glu; R.sup.30 represents the residue of a neutral genetically encodable L-amino acid selected from the group consisting of Ala, Thr, and Ser; R.sup.31 represents 1, 2, or 3 neutral or basic alpha amino acids, wherein at least one of the alpha amino acids is selected from the group consisting of Arg, Lys, Hyl, Orn, Cit, and His; X represents His at position B10; and the sequences A1 to A20 and B1 to B29 in Formula II correspond to a mammalian insulin; excluding those insulin derivatives in which simultaneously: R.sup.1 at position B1 denotes Phe; and R.sup.3 is one alpha amino acid having a terminal carboxyl group.
Inventor(s):	Dorschug; Michael (Bochum, DE)
Assignee:	Hoechst Aktiengesellschaft (Frankfurt am Main, DE)
Application Number:	08/304,593
Patent Claims:	1. An insulin derivative having an isoelectric point between 5 and 8.5, or a physiologically tolerated salt thereof, of the Formula II in which: ##STR10## R.sup.1 at position B1 denotes H or H-Phe; R.sup.2 at position A21 denotes a genetically encodable L-amino acid selected from the group consisting of Gly, Ala, Val, Leu, Ile, Pro, Phe, Trp, Met, Ser, Thr, Cys, Tyr, Asp, and Glu; R.sup.30 represents the residue of a neutral genetically encodable L-amino acid selected from the group consisting of Ala, Thr, and Ser; R.sup.31 represents 1, 2, or 3 neutral or basic .alpha.-amino acids, wherein at least one of the .alpha.-amino acids is selected from the group consisting of Arg, Lys, Hyl, Orn, Cit, and His; X represents His at position B10; and the sequences A1 to A20 and B1 to B29 in Formula II correspond to a mammalian insulin; excluding those insulin derivatives in which simultaneously: R.sup.1 at position B1 denotes Phe; and R.sup.31 is one alpha amino acid having a terminal carboxyl group. 2. An insulin derivative or the physiologically tolerated salts thereof as claimed in claim 1, wherein R.sup.1 in formula II represents H-Phe. 3. An insulin derivative or the physiologically tolerated salts thereof as claimed in claim 1, wherein R.sup.2 in formula II represents Gly, Ala, Ser, Thr, Asp, or Glu. 4. An insulin derivative or the physiologically tolerated salts thereof as claimed in claim 1, wherein R.sup.31 in formula II represents Arg-Arg-OH. 5. An insulin derivative or the physiologically tolerated salts thereof as claimed in claim 1, wherein the sequences (A1 to A20) and (B1 to B29) in formula II are the sequences of human, porcine, or bovine insulin. 6. A pharmaceutical composition that contains an effective amount of at least one insulin derivative of the formula II, or at least one of the physiologically tolerated salts thereof, as claimed in claim 1, in dissolved, amorphous or crystalline form for the treatment of diabetes. 7. A pharmaceutical composition as claimed in claim 6, which additionally contains 1 .mu.g to 2 mg of zinc/ml. 8. A pharmaceutical composition as claimed in claim 6, which additionally contains unmodified insulin. 9. A method for treating a patient suffering from diabetes mellitus, which comprises administering to said patient a pharmaceutical composition as claimed in claim 6. 10. An insulin derivative or the physiologically tolerated salts thereof as claimed in claim 3, wherein R.sup.2 in formula II represents Asp. 11. An insulin derivative or the physiologically tolerated salts thereof as claimed in claim 5, wherein the sequences (A1 to A20) and (B1 to B29) in formula II are the sequences of human insulin. 12. A pharmaceutical composition that contains an effective amount of at least one insulin derivative of the formula II, or at least one of the physiologically tolerated salts thereof, as claimed in claim 8, in dissolved form for the treatment of diabetes. 13. A pharmaceutical composition as claimed in claim 7, which additionally contains 5 .mu.g to 200 .mu.g of zinc/ml. 14. A pharmaceutical composition as claimed in claim 8, wherein said unmodified insulin is unmodified human insulin. 15. An insulin derivative or the physiologically tolerated salts thereof as claimed in claim 5, wherein R.sup.1 represents H-Phe, R.sup.2 represents Gly, R.sup.30 represents Thr, and R.sup.31 represents Arg-Arg-OH.

Details for Patent 5,656,722

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Sanofi-aventis U.s. Llc	LANTUS	insulin glargine	Injection	021081	April 20, 2000		2014-08-12
Sanofi-aventis U.s. Llc	LANTUS	insulin glargine	Injection	021081	April 25, 2007		2014-08-12

International Patent Family for US Patent 5,656,722

Country	Patent Number	Estimated Expiration
South Africa	898456
United States of America	6100376
Portugal	92220
Philippines	30695