HANP-Fc-containing molecular conjugate

Patent metadata

Field	Value
Publication number	US-11008392-B2
Application number	US-201716314411-A
Country	US
Kind code	B2
Filing date	Jun 30, 2017
Priority date	Jul 1, 2016
Publication date	May 18, 2021
Grant date	May 18, 2021

Abstract

The present invention provides a conjugate comprising a hANP peptide bonded via a polyethylene glycol linker to a glycan attached to Asn297 of a Fc-containing molecule (N297 glycan), or a pharmaceutically acceptable salt thereof, a medicament comprising the same as an active ingredient, a method for producing the same, etc.

First claim

The invention claimed is:

1. A method for producing a desired Fc-containing molecule comprising a complex N297 glycan, the method comprising reacting a glycan donor comprising a complex glycan with an unactivated reducing end, an initial Fc-containing molecule comprising an acceptor N297 glycan, an Endo enzyme (enzyme A) which recognizes the complex glycan of the glycan donor but not the acceptor N297 glycan as its substrate, and another Endo enzyme (enzyme B) which recognizes the acceptor N297 glycan as its substrate, in a reaction solution,
wherein the glycan donor is (MSG1-) Asn, (MSG2-) Asn, SGP or (SG-) Asn,
wherein the acceptor N297 glycan is GlcNAc or (Fuca1, 6) GlcNAc,
wherein the enzyme A is EndoM, EndoCC, EndoOm, EndoM N175Q, EndoCC N180H, or EndoOm N194Q, and
wherein the enzyme B is EndoS, EndoS2, EndoS D233Q, EndoS D233Q/Q303L, EndoS D233Q/E350A, EndoS D233Q/E350Q, EndoS D233Q/E350D, EndoS D233Q/E350N, or EndoS D233Q/D405A.

2. The method according to claim 1 , further comprising purifying the desired Fc-containing molecule from the reaction solution.

3. The method according to claim 1 , wherein the glycan donor is a molecule comprising a N-linked glycan or a O-linked glycan.

4. The method according to claim 3 , wherein the complex glycan in the glycan donor comprises a non-reducing end which is chemically modified.

5. The method according to claim 1 , wherein the complex glycan in the glycan donor comprises a non-reducing end which is chemically modified.

6. The method according to claim 1 , wherein the desired Fc-containing molecule is an IgG, CLCH or Fc fragment.

7. The method according to claim 5 , wherein the chemical modification on the non-reducing end is introduction of an azide group to the sialic acid in the non-reducing end.

8. The method of claim 7 , further comprising the step of reacting a molecule comprising DBCO with the azide group.

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Iwamoto Mitsuhiro
• Oishi Shohei
• Sekiguchi Yukiko
• Chaya Hiroyuki
• Miyauchi Ryuki
• Honda Takeshi

Classifications

• A61P9/10 Primary

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C12P19/18

  produced by the action of a glycosyl transferase, e.g. alpha-, beta- or gamma-cyclodextrins · CPC title

• C07K14/58 Primary

  Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Cardionatrin; Cardiodilatin · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title