Process for preparing insulin analogs
First Claim
Patent Images
1. A process for preparing a therapeutically active insulin analog of the formula;
- ##STR9## or a pharmaceutically acceptable salt thereof, wherein A21 is Asn, or Ala;
B1 is Phe, or is absent;
B2 is Val, or is absent;
B10 is His, or Asp;
B28 is any amino acid;
B29 is L-Pro, D-Pro, L-hydroxyproline, D-hydroxyproline; and
,B30 is Thr, Ala, or is absent;
said method comprising;
i) transforming a host cell with DNA that encodes a proinsulin-like precursor molecule having the A and B chains of Formula (I);
ii) culturing the recombinant host cell under conditions suitable for expressing the DNA used to transform the host cell and isolating the proinsulin-like precursor molecule encoded by the DNA in step i);
iii) enzymatically cleaving the proinsulin-like precursor molecule to remove the connecting peptide; and
,iv) recovering the insulin analog.
0 Assignments
0 Petitions
Accused Products
Abstract
Recombinant processes for preparing insulin analogs modified at position 29 of the B-chain and, optionally, at other positions are claimed. The analogs produced using the claimed processes have modified physico-chemical properties and are useful in treating hyperglycemia.
-
Citations
20 Claims
-
1. A process for preparing a therapeutically active insulin analog of the formula;
- ##STR9## or a pharmaceutically acceptable salt thereof, wherein A21 is Asn, or Ala;
B1 is Phe, or is absent; B2 is Val, or is absent; B10 is His, or Asp; B28 is any amino acid; B29 is L-Pro, D-Pro, L-hydroxyproline, D-hydroxyproline; and
,B30 is Thr, Ala, or is absent;
said method comprising;i) transforming a host cell with DNA that encodes a proinsulin-like precursor molecule having the A and B chains of Formula (I); ii) culturing the recombinant host cell under conditions suitable for expressing the DNA used to transform the host cell and isolating the proinsulin-like precursor molecule encoded by the DNA in step i); iii) enzymatically cleaving the proinsulin-like precursor molecule to remove the connecting peptide; and
,iv) recovering the insulin analog. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
- ##STR9## or a pharmaceutically acceptable salt thereof, wherein A21 is Asn, or Ala;
-
10. A process for preparing a therapeutically active insulin analog of the formula;
- ##STR10## or a pharmaceutically acceptable salt thereof;
said method comprising;
i) transforming a host cell with DNA that encodes a proinsulin-like precursor molecule having the A and B chains of Formula (II);ii) culturing the recombinant host cell under conditions suitable for expressing the DNA used to transform the host cell and isolating the proinsulin-like precursor molecule encoded by the DNA in step i); iii) enzymatically cleaving the proinsulin-like precursor molecule to remove the connecting peptide; and
,iv) recovering the insulin analog.
- ##STR10## or a pharmaceutically acceptable salt thereof;
-
11. A process for preparing a therapeutically active insulin analog of the formula;
- ##STR11## or a pharmaceutically acceptable salt thereof, wherein A21 is Asn, or Ala;
B1 is Phe, or is absent; B2 is Val, or is absent; B10 is His, or Asp; B28 is any amino acid; B29 is L-Pro, D-Pro, L-hydroxyproline, D-hydroxyproline; and
,B30 is Thr, Ala, or is absent;
said method comprising;i) transforming a host cell with DNA that individually encodes the A and B chains of Formula (I); ii) culturing the recombinant host cell under conditions suitable for expressing the DNA used to transform the host cell and isolating the A and B chains of Formula (I) encoded by the DNA in step i); iii) combining the individual A and B chains to produce a insulin analog of Formula (I); and
,iv) recovering the insulin analog. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19)
- ##STR11## or a pharmaceutically acceptable salt thereof, wherein A21 is Asn, or Ala;
-
20. A process for preparing a therapeutically active insulin analog of the formula;
- ##STR12## or a pharmaceutically acceptable salt thereof;
said method comprising;
i) transforming a host cell with DNA that encodes a proinsulin-like precursor molecule having the A and B chains of Formula (I);ii) culturing the recombinant host cell under conditions suitable for expressing the DNA used to transform the host cell and isolating the proinsulin-like precursor molecule encoded by the DNA in step i); iii) enzymatically cleaving the proinsulin-like precursor molecule to remove the connecting peptide; and
,iv) recovering the insulin analog.
- ##STR12## or a pharmaceutically acceptable salt thereof;
Specification