JPWO2021026203A5 - - Google Patents

Description

In some embodiments, the SCIT regimen comprises a cluster SCIT regimen. In some embodiments, the cluster SCIT regimen comprises an escalating regimen followed by a maintenance regimen, wherein the escalating regimen is over a period of 4-12 weeks (eg, 4, 5, 6, 7, 8, 9, 10, increasing doses of grass over a period of 11, or 12 weeks, such as 4-10 weeks, 4-8 weeks, 6-12 weeks, 6-10 weeks, 6-8 weeks, 8-12 weeks, or 8-10 weeks The maintenance regimen includes administering one or more maintenance doses of the highest dose of the herbal extract administered during the escalating regimen. In some embodiments, the escalating regimen comprises administering increasing doses of the herbal extract over a period of 8 weeks. In some embodiments, the maintenance regimen is maintained every 1-4 weeks for at least 8 weeks (eg, for at least 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks, or longer). including administering a dose. In some embodiments, the titration regimen comprises escalating from a dose of 1 Bioequivalent Allergic Unit (BAU) to a dose of at least about 4,000 BAU (e.g., 4, 5, 6, 7, 8, 9 , 10, 11, or 12 weeks), the maintenance regimen comprises administering one or more maintenance doses of at least about 4,000 BAU. In some embodiments, the escalating regimen comprises escalating from a dose of 1 Bioequivalent Allergic Unit (BAU) to a dose of 4,000 BAU (e.g., 4, 5, 6, 7, 8, 9, 10 , 11, or 12 weeks), the maintenance regimen comprises administering one or more maintenance doses of 4,000 BAU.

Claims (28)

An interleukin-4 receptor (IL-4R) antagonist for use in a method for enhancing the efficacy and/or tolerability of a grass allergen-specific subcutaneous immunotherapy (SCIT) regimen in a subject with a grass allergy A pharmaceutical composition, the method comprising administering to the subject one or more doses of an IL-4R antagonist in combination with the SCIT regimen, wherein at least one dose of the IL-4R antagonist is , administered prior to initiation of said SCIT regimen, wherein said IL-4R antagonist comprises a heavy chain complementarity determining region (HCDR) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:1 and an amino acid sequence of SEQ ID NO:2 The pharmaceutical composition, which is an anti-IL-4R antibody or an antigen-binding fragment thereof comprising a light chain complementarity determining region (LCDR) of a light chain variable region (LCVR) comprising: The SCIT regimen consists of subcutaneous administration of a herbal extract derived from a grass selected from the group consisting of: Timothy, Bahia, Bermuda, Sorghum, Kentucky Bluegrass, Orchard, Knotweed, Rye, Harugaya, Big fescue, and combinations thereof. 2. The pharmaceutical composition of claim 1, comprising 3. The pharmaceutical composition according to claim 2, wherein the herbal extract is derived from Rhododendron japonicum. The pharmaceutical composition according to any one of claims 1-3, wherein the SCIT regimen comprises a cluster SCIT regimen. A cluster SCIT regimen comprises an escalating regimen followed by a maintenance regimen comprising administering increasing doses of the herbal extract over a period of 4-12 weeks, the maintenance regimen being administered during the escalating regimen. 5. The pharmaceutical composition of claim 4, comprising administering one or more maintenance doses of the highest dose of said herbal extract administered. 6. The pharmaceutical composition of claim 5, wherein the escalating regimen comprises administering increasing doses of the herbal extract over a period of 8 weeks. 7. The pharmaceutical composition of claim 5 or 6, wherein the maintenance regimen comprises administering a maintenance dose every 1-4 weeks for at least 8 weeks. An ascending regimen involves escalating from a dose of 1 Bioequivalent Allergic Unit (BAU) to a dose of 4,000 BAU, and a maintenance regimen involves administering one or more maintenance doses of 4,000 BAU. , the pharmaceutical composition according to any one of claims 5-7. 9. The pharmaceutical composition of any one of claims 1-8, wherein the IL-4R antagonist is administered at a dose of about 75 mg to about 600 mg. of claims 1-9, wherein the IL-4R antagonist is administered in an initial dose followed by one or more secondary doses, each secondary dose administered 1-4 weeks after the immediately preceding dose. A pharmaceutical composition according to any one of claims 1 to 3. 11. The pharmaceutical composition of claim 10, wherein the initial dose of IL-4R antagonist is administered 1-7 days prior to initiation of the SCIT regimen. 12. A pharmaceutical composition according to claim 10 or 11, wherein the initial dose comprises 600 mg IL-4R antagonist and each secondary dose comprises 300 mg IL-4R antagonist. A pharmaceutical composition according to any one of claims 10-12, wherein each secondary dose is administered two weeks after the immediately preceding dose. 14. The pharmaceutical composition of any one of claims 1-13, wherein the IL-4R antagonist and SCIT are not administered to the subject on the same day. 15. The pharmaceutical composition of any one of claims 1-14, wherein enhancing efficacy and/or tolerability of a SCIT regimen comprises reducing allergic rhinitis symptoms in a subject. Enhanced efficacy and/or tolerability of SCIT regimens
(a) increasing the amount of serum grass allergen-specific IgG4 (sIgG4) in a subject compared to SCIT monotherapy;
(b) reducing the amount of serum grass allergen-specific IgE (sIgE) in said subject compared to SCIT monotherapy; and/or (c) reducing the amount of sIgG4 to sIgE in said subject compared to SCIT monotherapy A pharmaceutical composition according to any one of claims 1 to 15, comprising increasing ratios. 17. The pharmaceutical composition of any one of claims 1-16, wherein administration of an IL-4R antagonist in combination with a SCIT regimen reduces or inhibits induction of sIgE during a SCIT titration regimen and/or a SCIT maintenance regimen. 18. The pharmaceutical composition of any one of claims 1-17, wherein administration of the IL-4R antagonist in combination with a SCIT regimen increases the maximum SCIT dose tolerated by the subject. 19. The pharmaceutical composition of any one of claims 1-18, wherein administration of an IL-4R antagonist in combination with a SCIT regimen reduces the use of epinephrine or oral steroids as rescue agents. The anti-IL-4R antibody or antigen-binding fragment thereof comprises three HCDRs (HCDR1, HCDR2, and HCDR3) and three LCDRs (LCDR1, LCDR2, and LCDR3), wherein HCDR1 has the amino acid sequence of SEQ ID NO:3. said HCDR2 comprises the amino acid sequence of SEQ ID NO:4; said HCDR3 comprises the amino acid sequence of SEQ ID NO:5; said LCDR1 comprises the amino acid sequence of SEQ ID NO:6; said LCDR2 comprises the amino acid sequence of SEQ ID NO:7 the pharmaceutical composition of any one of claims 1-19, wherein said LCDR3 comprises the amino acid sequence of SEQ ID NO:8. 21. The anti-IL-4R antibody or antigen-binding fragment thereof according to any one of claims 1 to 20, comprising HCVR comprising the amino acid sequence of SEQ ID NO: 1, and comprising LCVR comprising the amino acid sequence of SEQ ID NO: 2. pharmaceutical composition. 22. The pharmaceutical composition of any one of claims 1-21, wherein the anti-IL-4R antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:9 and a light chain comprising the amino acid sequence of SEQ ID NO:10. The pharmaceutical composition according to any one of claims 1-22, wherein the IL-4R antagonist is dupilumab or a biological equivalent thereof. 24. The IL-4R antagonist of any one of claims 1-23, wherein the IL-4R antagonist is contained in a container selected from the group consisting of glass vials, syringes, pre-filled syringes, pen delivery devices, and autoinjectors. pharmaceutical composition. 25. The pharmaceutical composition of Claim 24, wherein the IL-4R antagonist is contained in a pre-filled syringe. 26. The pharmaceutical composition of Claim 25, wherein the pre-filled syringe is a single dose pre-filled syringe. 25. The pharmaceutical composition of claim 24, wherein the IL-4R antagonist is contained in an autoinjector. 25. The pharmaceutical composition of Claim 24, wherein the IL-4R antagonist is contained in a pen delivery device.