IP Library › Granted Patent US 12,296,021
Granted Patent B2
US 12,296,021 · App. 17/888,336 · Granted May 13, 2025

Antibody conjugates and methods of making and using the same

Inventors: Yun Cheol Kim (Walnut Creek, CA); Chao Bai Huang (San Leandro, CA); Penelope M. Drake (Castro Valley, CA); David Rabuka (Kensington, CA)
Assignee: R.P. Scherer Technologies, LLC
A61K47/6849A61K47/60A61K47/6851A61K49/0002C07K16/30C07K2317/52
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Quick Facts
Patent No.
US 12,296,021
App. No.
17/888,336
Granted
May 13, 2025
Kind
B2
Abstract

Antibodies that include a sulfatase motif-containing tag in a constant region of an immunoglobulin (Ig) heavy chain polypeptide are disclosed. The sulfatase motif can be converted by a formylglycine-generating enzyme (FGE) to produce a formylglycine (fGly)-modified Ig heavy chain polypeptide. An fGly-modified Ig heavy chain polypeptide of the antibody can be covalently and site-specifically bound to a moiety of interest to provide an antibody conjugate. The disclosure also encompasses methods of production of such tagged Ig heavy chain polypeptides, fGly-modified Ig heavy chain polypeptides, and antibody conjugates, as well as methods of use of same.

Claims (15)

1. An antibody comprising an immunoglobulin (Ig) heavy chain polypeptide and an Ig light chain polypeptide, wherein:

excluding a sulfatase motif having the amino acid sequence of LCTPSR (SEQ ID NO: 561, the Ig heavy chain polypeptide has 97% or more sequence identity to the amino acid sequence set forth in SEQ ID NO: 656, and wherein

the Ig heavy chain polypeptide comprises an insertion of the sulfatase motif (LCTPSR (SEQ ID NO: 561)) before the glutamine residue at the 58 th position of the amino acid sequence set forth in SEQ ID NO: 1 thereby producing in the Ig heavy chain polypeptide the amino acid sequence of AVLLCTPSRQSS (SEQ ID NO: 657).

2. The antibody of claim 1 , wherein Ig heavy chain polypeptide comprises the amino acid sequence of SEQ ID NO: 656.

3. The antibody of claim 1 , wherein, in the Ig heavy chain polypeptide, the cysteine residue in the sulfatase motif (LCTPSR (SEQ ID NO: 561)) is oxidized to fGly.

4. The antibody of claim 3 , wherein, in the Ig heavy chain polypeptide, fGly is covalently bound to a payload.

5. The antibody of claim 4 , wherein the Ig heavy chain polypeptide is covalently bound to the payload via a hydrazone, oxime, semicarbazone, alkyl, alkenyl, acyloxy, hydrazinyl-indolyl, hydrazinyl-imidazoyl, hydrazinyl-pyrrolyl, hydrazinyl-furanyl or a pyrazalinone linkage.

6. The antibody of claim 4 , wherein the Ig heavy chain polypeptide is covalently bound to the payload via a linking group.

7. The antibody of claim 6 , wherein the linking group comprises a 4-aminopiperidine derivative (4AP).

8. The antibody of claim 4 , wherein the payload is selected from a drug, a detectable label, a water-soluble polymer, and a synthetic peptide.

9. The antibody of claim 4 , wherein the payload is a small molecule drug.

10. The antibody of claim 9 , wherein the small molecule drug is a cancer chemotherapeutic agent selected from the group consisting of an alkylating agent, a nitrosourea, an antimetabolite, an antitumor antibiotic, a vinca alkaloid, and a steroid hormone.

11. The antibody of claim 8 , wherein the water-soluble polymer is poly (ethylene glycol).

12. The antibody of claim 8 , wherein the detectable label is an imaging agent.

13. The antibody of claim 4 , wherein the payload is a viral fusion inhibitor.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 9, 2022
From: KIM, YUN CHEOL; HUANG, CHAO BAI; DRAKE, PENELOPE M.; RABUKA, DAVID
To: R.P. SCHERER TECHNOLOGIES, LLC
Reel/Frame 061707/0436 →
Continuity (3)
Division 16491124
Provisional Application 62473161 · Mar 17, 2017
Related Publication 20230235079A1 · Jul 27, 2023
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