Process for preparing insulin analogs
AssigneeEli Lilly and Company
InventorsRonald E. Chance, Richard D. DiMarchi, Bruce H. Frank, James E. Shields
Life of this patent
Estimating the term…
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.
Claims20
A process for preparing a therapeutically active insulin analog of the formula;
- ##STR9## or a pharmaceutically acceptable salt thereof, wherein A.sub.21 is Asn, or Ala;
- B.sub.1 is Phe, or is absent;
- B.sub.2 is Val, or is absent;
- B.sub.10 is His, or Asp;
- B.sub.28 is any amino acid;
- B.sub.29 is L-Pro, D-Pro, L-hydroxyproline, D-hydroxyproline;
- and,
- B.sub.30 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.
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.
A process for preparing a therapeutically active insulin analog of the formula;
- ##STR11## or a pharmaceutically acceptable salt thereof, wherein A.sub.21 is Asn, or Ala;
- B.sub.1 is Phe, or is absent;
- B.sub.2 is Val, or is absent;
- B.sub.10 is His, or Asp;
- B.sub.28 is any amino acid;
- B.sub.29 is L-Pro, D-Pro, L-hydroxyproline, D-hydroxyproline;
- and,
- B.sub.30 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.
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.
Dependencies are inferred from the claim text.