Pharmaceutical formulations containing anti-ox40l antibodies

Patent metadata

Field	Value
Publication number	US-2024392021-A1
Application number	US-202418634191-A
Country	US
Kind code	A1
Filing date	Apr 12, 2024
Priority date	Apr 14, 2023
Publication date	Nov 28, 2024
Grant date	—

Abstract

The present disclosure provides aqueous pharmaceutical formulations comprising anti-OX40L antibodies or antigen binding fragment thereof for treating or preventing OX40L-mediated diseases or conditions in humans. The present disclosure also provides containers and kits comprising the aqueous pharmaceutical formulations and the use of these aqueous pharmaceutical formulations in treating or preventing OX40L-mediated diseases or conditions in humans.

First claim

1 . An aqueous pharmaceutical formulation comprising:
(a) an anti-OX40 ligand (OX40L) antagonist antibody or antigen binding fragment thereof, (b) a stabilizer; (c) a chelator; (d) a surfactant; and (e) a buffer comprising histidine or a histidine salt; wherein the pH of the aqueous pharmaceutical formulation ranges from 5.5 to about 6.5, wherein:
(i) the antibody or antigen binding fragment thereof comprises:
the heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, the HCDR2 of SEQ ID NO:44, and the HCDR3 of SEQ ID NO: 46; and
the light chain complementarity determining region (LCDR) 1 of SEQ ID NO:56, the LCDR2 of SEQ ID NO:58, and the LCDR3 of SEQ ID NO: 60; or

(ii) the antibody or antigen binding fragment thereof comprises:
the heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 36, the HCDR2 of SEQ ID NO: 38, and the HCDR3 of SEQ ID NO: 40; and
the light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 50, the LCDR2 of amino acid sequence AAS, and the LCDR3 of SEQ ID NO: 54, or

(iii) the antibody or antigen binding fragment thereof comprises a variable heavy (VH) domain comprising at least 80% identity to the amino acid sequence of SEQ ID NO: 34 and a variable light (VL) domain having at least 80% identity to the amino acid sequence of SEQ ID NO: 48; or
(iv) the antibody or antigen binding fragment thereof comprises:
a VH domain which comprises the HCDR1 sequence of SEQ ID NO: 36 or 42, the HCDR2 sequence of SEQ ID NO: 38 or 44, and the HCDR3 sequence of SEQ ID NO: 40 or 46; and
a VL domain which comprises the LCDR1 sequence of SEQ ID NO: 50 or 56, the LCDR2 sequence of SEQ ID NO: 52 or 58, and the LCDR3 sequence of SEQ ID NO: 54 or 60; or

(v) the VL domain comprises the amino acid sequence of SEQ ID NO:48 and the VH domain comprises the amino acid sequence of SEQ ID NO:34; or
(vi) the antibody comprises a heavy chain and a light chain, wherein the heavy chain amino acid sequence consists of the amino acid sequence of SEQ ID NO: 62 and the light chain amino acid sequence consists of the amino acid sequence of SEQ ID NO: 64,
wherein the aqueous pharmaceutical formulation is suitable for parenteral administration to a mammalian subject.

2 . (canceled)

3 . (canceled)

4 . The aqueous pharmaceutical formulation of claim 1 , wherein:
the antibody or antigen binding fragment comprises a VH domain comprising at least 80% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 34 and/or comprises a VL domain comprising at least 80% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 48; or the antibody or antigen binding fragment comprises the heavy chain of SEQ ID NO: 62 and the light chain of SEQ ID NO: 64; or the antibody is amlitelimab or a variant thereof.

5 - 7 . (canceled)

8 . The aqueous pharmaceutical formation of claim 1 , wherein the aqueous pharmaceutical formulation is suitable for parenteral administration to a mammalian subject, optionally wherein the aqueous pharmaceutical formulation is suitable for subcutaneously delivery.

9 . The aqueous pharmaceutical formulation of claim 1 , wherein the antibody or antigen binding fragment thereof is present at a concentration of 62.5 mg/mL or 125 mg/mL.

10 . (canceled)

11 . The aqueous pharmaceutical formulation of claim 1 , wherein the stabilizer is sucrose, optionally wherein the sucrose is present in an amount of 220 mM.

12 . (canceled)

13 . The aqueous pharmaceutical formulation of claim 1 , wherein the surfactant is polysorbate 80, optionally wherein the polysorbate 80 is present in a concentration of from 0.02% (w/v) to 0.1% (w/v), from 0.02% (w/v) to 0.06%, or from 0.04% (w/v) or 0.06% (w/v).

14 - 16 . (canceled)

17 . The aqueous pharmaceutical formulation of claim 1 , wherein the buffer comprises 10 mM L-histidine or histidine hydrochloride.

18 . The aqueous pharmaceutical formulation of claim 1 , wherein the chelator is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), diethylenetriamene pentaacetate (DTPA) and salts thereof, and any combinations thereof, optionally wherein the chelator comprises one or both of 10 μM EDTA and 10 μM DTPA.

19 . (canceled)

20 . The aqueous pharmaceutical formulation of claim 1 , comprising:
28 mg/mL to 138 mg/mL of the antibody or antigen binding fragment thereof; 10 mM±1.5 mM L-histidine or histidine hydrochloride; 220 mM±33 mM sucrose, 0.06% (w/v) polysorbate 80; and water, wherein the pH of the aqueous pharmaceutical formulation is between about 5.8 and about 6.2.

21 . The aqueous pharmaceutical formulation of claim 20 , further comprising 10 μM EDTA or 10 μM DTPA, optionally wherein the aqueous pharmaceutical formulation is housed in a container, or suitable for subcutaneously delivery.

22 - 24 . (canceled)

25 . A pharmaceutical unit dosage form suitable for parenteral administration to a mammalian subject which comprises the aqueous pharmaceutical formulation of claim 1 in a suitable container, optionally wherein the aqueous pharmaceutical formulation is suitable for intravenous, subcutaneous, or intramuscular administration, or optionally wherein the suitable container is a pre-filled syringe.

26 . (canceled)

27 . (canceled)

28 . A sealed container comprising the aqueous pharmaceutical formulation of claim 1 .

29 . The sealed container of claim 28 , which is a vial, a syringe, a microinfusor, a pen delivery device, or an autoinjector, optionally wherein the sealed container is a single or multi-chambered syringe, or optionally wherein the sealed container is a pre-filled syringe or pen.

30 . (canceled)

31 . A container comprising an aqueous pharmaceutical formulation comprising:
about 28 mg/mL to about 138 mg/mL of an anti-OX40 ligand (OX40L) antagonist antibody or antigen binding fragment thereof, about 10 mM L-histidine or histidine hydrochloride; about 220 mM sucrose; about 0.06% (w/v) polysorbate 80; about 10 μM EDTA; and water, wherein the pH of the aqueous pharmaceutical is about 6.0, and wherein the container is a pre-filled syringe, a pre-filled pen, or an autoinjector, optionally wherein the antibody or antigen binding fragment thereof is present at a concentration of 62.5 mg/mL or 125 mg/mL.

32 - 34 . (canceled)

35 . The container of claim 31 , wherein the anti-OX40 ligand (OX40L) antagonist antibody or antigen binding fragment thereof comprises:
(a) the heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, the HCDR2 of SEQ ID NO:44, and the HCDR3 of SEQ ID NO:46; and the light chain complementarity determining region (LCDR) 1 of SEQ ID NO:56, the LCDR2 of SEQ ID NO:58, and the LCDR3 of SEQ ID NO:60; or (b) the heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 36, the HCDR2 of SEQ ID NO:38, and the HCDR3 of SEQ ID NO:40; and the light chain complementarity determining region (LCDR) 1 of SEQ ID NO:50, the LCDR2 of SEQ ID NO:52, and the LCDR3 of SEQ ID NO:54; or (c) the VH domain comprising at least 80% identity to the amino acid sequence of SEQ ID NO: 34 and the VL domain having at least 80% identity to the amino acid sequence of SEQ ID NO: 48; or (d) the VH domain comprising at least 80% identity to the amino acid sequence of SEQ ID NO: 34 and/or comprises the VL domain having at least 80% identity to the amino acid sequence of SEQ ID NO

Assignees

• Kymab Ltd

Inventors

• Zhu Chen
• Gupta Ashi
• Gooding Tamera
• Patke Sanket
• Badiali Luca
• Jörg Susanne
• Engelke Laura

Classifications

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/2875 Primary

  against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241) · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title