CN118078988A - Pharmaceutical compositions comprising antibodies targeting IL-17A - Google Patents

Pharmaceutical compositions comprising antibodies targeting IL-17A Download PDF

Info

Publication number
CN118078988A
CN118078988A CN202410479487.XA CN202410479487A CN118078988A CN 118078988 A CN118078988 A CN 118078988A CN 202410479487 A CN202410479487 A CN 202410479487A CN 118078988 A CN118078988 A CN 118078988A
Authority
CN
China
Prior art keywords
pharmaceutical composition
mmol
antibody
buffer
seq
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202410479487.XA
Other languages
Chinese (zh)
Inventor
孔令婕
刘成军
李盈淳
杨春燕
刘姝慧
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Nanjing Shunxin Pharmaceutical Co Ltd
Original Assignee
Chia Tai Tianqing Pharmaceutical Group Co Ltd
Nanjing Shunxin Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chia Tai Tianqing Pharmaceutical Group Co Ltd, Nanjing Shunxin Pharmaceutical Co Ltd filed Critical Chia Tai Tianqing Pharmaceutical Group Co Ltd
Priority to CN202410479487.XA priority Critical patent/CN118078988A/en
Publication of CN118078988A publication Critical patent/CN118078988A/en
Pending legal-status Critical Current

Links

Landscapes

  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention relates generally to the field of antibody formulations. The invention provides an antibody pharmaceutical composition comprising an IL-17A targeting antibody or antigen binding fragment thereof, a buffer, a surfactant and a stabilizer, said pharmaceutical composition having superior stability.

Description

Pharmaceutical compositions comprising antibodies targeting IL-17A
Technical Field
The invention relates to the field of antibody preparations, in particular to a stable pharmaceutical composition containing an anti-IL-17A antibody or an antigen binding fragment thereof.
Background
IL-17A is a central lymphokine of the Th17 cell subset of inflammatory T cells, inducing and mediating the expression of a variety of cytokines, and has a very critical role in autoimmune and inflammatory processes. The treatment of IL-17A as a target in the current clinical trial has achieved very good results in psoriasis, plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, ankylosing spondylitis, inflammatory bowel disease, multiple sclerosis, non-radiological axial spondyloarthritis and rheumatoid arthritis.
For antibodies, which have large molecular weights, complex structures, are susceptible to degradation, aggregation, or become unstable by undesired chemical modifications, however, any instability may affect the safety and effectiveness of the therapeutic antibody, and thus, the therapeutic antibody needs to be formulated in a suitable formulation to prevent disruption of antibody structure and activity due to denaturation, oxidation, aggregation, etc. of the antibody during storage, transport, and administration. In addition, when the antibody is present at a high concentration, there are problems such as high level of aggregation, higher osmotic pressure than physiological, and low injectability due to an increase in viscosity. The smaller volume of the administration preparation can not only improve the compliance of patients to the therapy, but also save the cost. Therefore, it is necessary to develop a stable pharmaceutical composition containing a high concentration of mab.
Disclosure of Invention
The present invention provides a pharmaceutical composition, wherein the pharmaceutical composition comprises a high concentration of an anti-IL-17A antibody or antigen-binding fragment thereof, retains biological activity and stability during storage, and is free of high levels of aggregation.
The invention provides a pharmaceutical composition, wherein the pharmaceutical composition comprises: an anti-IL-17A antibody or antigen-binding fragment thereof, a buffer, a stabilizer, and a surfactant.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof is capable of specifically binding to IL-17A (e.g., human IL-17A) and/or blocking IL-17A signaling, including, but not limited to, polyclonal antibodies, monoclonal antibodies, multispecific antibodies, monospecific antibodies, monovalent antibodies, and single chain antibodies.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof is contained in the pharmaceutical composition at a concentration of 20-200 mg/mL, 50-150 mg/mL, 60-120 mg/mL, or 70-90 mg/mL, preferably at a concentration of 60 mg/mL, 65 mg/mL, 70 mg/mL, 75 mg/mL, 80 mg/mL, or 85 mg/mL, more preferably at a concentration of 80 mg/mL.
In some embodiments, the buffer in the pharmaceutical composition may be selected from phosphate buffer, tris buffer, citrate buffer, carbonate buffer, acetate buffer or histidine salt buffer, preferably the buffer in the pharmaceutical composition is selected from acetate buffer or histidine salt buffer. In some embodiments, examples of the acetate buffer include sodium acetate buffer, potassium acetate buffer, or sodium acetate-acetate buffer, and examples of the histidine salt buffer include histidine-histidine hydrochloride buffer or histidine-acetate buffer.
In some embodiments, the concentration of buffer in the pharmaceutical composition is 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L, preferably the concentration of buffer in the pharmaceutical composition is 10 mmol/L, 15 mmol/L, 20 mmol/L, 25mmol/L, more preferably the concentration of buffer in the pharmaceutical composition is 20 mmol/L. In some specific embodiments, the concentration of the acetic acid-sodium acetate buffer in the pharmaceutical composition is 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L, preferably the concentration of the acetic acid-sodium acetate buffer in the pharmaceutical composition is 10 mmol/L, 15 mmol/L, 20 mmol/L, or 25mmol/L, more preferably the concentration of the acetic acid-sodium acetate buffer in the pharmaceutical composition is 20 mmol/L. In some specific embodiments, the concentration of histidine-histidine hydrochloride buffer in the pharmaceutical composition is 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L, preferably the concentration of histidine-histidine hydrochloride buffer in the pharmaceutical composition is 10 mmol/L, 15 mmol/L, 20 mmol/L, or 25mmol/L, more preferably the concentration of histidine-histidine hydrochloride buffer in the pharmaceutical composition is 20 mmol/L.
In some embodiments, the stabilizer in the pharmaceutical composition comprises a sugar alcohol (e.g., mannitol, sorbitol), a disaccharide (e.g., trehalose, sucrose, maltose, lactose), a monosaccharide (e.g., dextrose (D-glucose)), an amino acid (e.g., lysine, glycine, proline, arginine, or a pharmaceutically acceptable salt thereof), or a salt (e.g., sodium chloride), preferably the stabilizer in the pharmaceutical composition comprises sucrose.
In some embodiments, the concentration of the stabilizer in the pharmaceutical composition is 1-110 mg/mL, 40-110 mg/mL, 50-80 mg/mL, or 70-80 mg/mL, preferably the concentration of the stabilizer in the pharmaceutical composition is 70 mg/mL, 75 mg/mL, 80 mg/mL, 85 mg/mL, 90 mg/mL, 95 mg/mL, 100 mg/mL, 105 mg/mL, or 110 mg/mL, more preferably the concentration of the stabilizer in the pharmaceutical composition is 80 mmol/L. In some specific embodiments, the concentration of sucrose in the pharmaceutical composition is 1-110 mg/mL, 40-110 mg/mL, 50-80 mg/mL, or 70-80 mg/mL, preferably the concentration of sucrose in the pharmaceutical composition is 70 mg/mL, 75 mg/mL, 80 mg/mL, 85 mg/mL, 90 mg/mL, 95 mg/mL, 100 mg/mL, 105 mg/mL, or 110 mg/mL, more preferably the concentration of sucrose in the pharmaceutical composition is 80 mg/mL.
In some embodiments, the surfactant in the pharmaceutical composition is selected from the group consisting of polysorbates (e.g., polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 81, or polysorbate 85), poloxamers (e.g., poloxamer 181, poloxamer 188, or poloxamer 407), polyethylene glycols, or polyhydroxymers, and the like, preferably, the surfactant in the pharmaceutical composition is polysorbate 80.
In some embodiments, the concentration of surfactant in the pharmaceutical composition is 0.01-2 mg/mL, 0.05-1 mg/mL, 0.2-0.6 mg/mL, or 0.2-0.4 mg/mL, preferably the concentration of surfactant in the pharmaceutical composition is 0.3 mg/mL. In some embodiments, the concentration of polysorbate 80 in the pharmaceutical composition is 0.01-2 mg/mL, 0.05-1 mg/mL, 0.2-0.6 mg/mL, or 0.2-0.4 mg/mL, preferably the concentration of polysorbate 80 in the pharmaceutical composition is 0.3 mg/mL.
In some embodiments, the pharmaceutical composition has a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0. Preferably, the pH of the pharmaceutical composition is 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4 or 6.5. In some embodiments, the pharmaceutical composition has a pH of 5.0. In some embodiments, the pharmaceutical composition has a pH of 5.5. In some embodiments, the pharmaceutical composition has a pH of 6.0. In some embodiments, the pharmaceutical composition has a pH of 6.5.
In some embodiments, the pharmaceutical composition comprises: anti-IL-17A antibodies or antigen binding fragments thereof, acetate buffer, sucrose and polysorbate 80.
In some embodiments, the pharmaceutical composition comprises: anti-IL-17A antibodies or antigen binding fragments thereof, histidine salt buffer, sucrose and polysorbate 80.
In some embodiments, the pharmaceutical composition comprises: 20-200 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 1-50 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 1-110 mg/mL of a stabilizing agent (e.g., sucrose), and 0.01-2 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: 50-150 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 5-30 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 40-110 mg/mL of a stabilizing agent (e.g., sucrose), and 0.05-1 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: 60-120 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 10-25 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 50-80 mg/mL of a stabilizing agent (e.g., sucrose), and 0.2-0.6 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: 70-90 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 15-25 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 70-80 mg/mL of a stabilizing agent (e.g., sucrose), and 0.2-0.4 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of acetic acid-sodium acetate buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pharmaceutical composition having a pH of 5.5.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 5.0.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 5.5.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 6.0.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 6.5.
In some embodiments, an anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region comprising heavy chain CDR1 (HCDR 1), heavy chain CDR2 (HCDR 2), and heavy chain CDR3 (HCDR 3), wherein the heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3 comprise amino acid sequences having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequences shown in SEQ ID NOs 1,2, and 3, respectively. Wherein, the amino acid sequence of SEQ ID NO 1-3 is:
GYSFTDYHIH (SEQ ID NO: 1)；
VINPMYGTTDYNQRFKG (SEQ ID NO: 2)；
YDYFTGTGVY (SEQ ID NO: 3)。
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth in SEQ ID NO. 7. Wherein, the amino acid sequence of SEQ ID NO. 7 is:
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTDYHIHWVRQAPGQGLEWMGVINPMYGTTDYNQRFKGRVTITADESTSTAYMELSSLRSEDTAVYYCARYDYFTGTGVYWGQGTLVTVSS (SEQ ID NO: 7).
in some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain comprising an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence set forth in SEQ ID No. 9. Wherein, the amino acid sequence of SEQ ID NO. 9 is:
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTDYHIHWVRQAPGQGLEWMGVINPMYGTTDYNQRFKGRVTITADESTSTAYMELSSLRSEDTAVYYCARYDYFTGTGVYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 9).
In some embodiments, an anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a light chain variable region comprising light chain CDR1 (LCDR 1), light chain CDR2 (LCDR 2), and light chain CDR3 (LCDR 3), wherein the light chain CDR1, light chain CDR2, and light chain CDR3 comprise amino acid sequences that are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences shown in SEQ ID NOs 4,5, and 6, respectively. Wherein, the amino acid sequence of SEQ ID NO. 4-6 is:
RSSRSLVHSRGNTYLH (SEQ ID NO: 4)；
KVSNRFI (SEQ ID NO: 5)；
SQSTHLPFT (SEQ ID NO: 6)。
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a light chain variable region comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth in SEQ ID NO. 8. Wherein, the amino acid sequence of SEQ ID NO. 8 is:
DIVMTQTPLSLSVTPGQPASISCRSSRSLVHSRGNTYLHWYLQKPGQSPQLLIYVSNRFIGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHLPFTFGQGTKLEIK (SEQ ID NO: 8).
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a light chain comprising an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence set forth in SEQ ID No. 10. Wherein, the amino acid sequence of SEQ ID NO. 10 is:
DIVMTQTPLSLSVTPGQPASISCRSSRSLVHSRGNTYLHWYLQKPGQSPQLLIYKVSNRFIGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHLPFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 10).
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region and a light chain variable region, wherein heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3 comprise amino acid sequences that are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences set forth in SEQ ID NOs 1, 2, 3,4, 5, and 6, respectively. In some specific embodiments, the anti-IL-17A antibody or antigen binding fragment thereof comprises a heavy chain CDR1 as shown in SEQ ID NO. 1, a heavy chain CDR2 as shown in SEQ ID NO. 2, a heavy chain CDR3 as shown in SEQ ID NO. 3, a light chain CDR1 as shown in SEQ ID NO. 4, a light chain CDR2 as shown in SEQ ID NO. 5 and a light chain CDR3 as shown in SEQ ID NO. 6.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region and a light chain variable region comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to an amino acid sequence set forth in SEQ ID NOs 7 and 8, respectively. In some specific embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof comprises a heavy chain variable region as set forth in SEQ ID NO. 7 and a light chain variable region as set forth in SEQ ID NO. 8.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain and a light chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth in SEQ ID NOs 9 and 10, respectively. In some specific embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO. 9 and a light chain as set forth in SEQ ID NO. 10.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition may be a full length antibody, e.g., an IgG1, igG2, or IgG4 isotype full length antibody, preferably an IgG4 isotype full length antibody. In other embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition may be a single chain variable region (scFv) antibody, or an antibody fragment, such as a Fab or F (ab') 2 fragment.
The invention also provides a preparation method of the pharmaceutical composition, which comprises the following steps: mixing the anti-IL-17A antibody or antigen-binding fragment thereof, a buffer, a stabilizer, and further comprising adding a surfactant, in a sequential order, to prepare a pharmaceutical composition.
In some embodiments, the method of preparing further comprises the step of sterilizing the mixture obtained by mixing.
The invention also provides a freeze-dried preparation, which is obtained by freeze-drying the pharmaceutical composition.
The present invention also provides a lyophilized formulation that upon reconstitution (i.e., reconstitution) can form the pharmaceutical composition of the present invention.
The invention also provides a method of preparing a lyophilized formulation comprising an anti-IL-17A antibody or antigen-binding fragment thereof, comprising the step of lyophilizing the pharmaceutical composition. In some embodiments, the freeze-drying is performed according to methods well known in the art, including but not limited to the steps of prefreezing, primary drying, and secondary drying. Those skilled in the art will appreciate that any method of removing water from the pharmaceutical compositions of the present invention is suitable for use in the present invention.
The present invention also provides an article of manufacture comprising a container containing the aforementioned pharmaceutical composition or the aforementioned lyophilized formulation.
The pharmaceutical compositions or lyophilized formulations of the invention may be administered according to known methods, for example by injection or infusion over a period of time in a suitable manner, for example, by subcutaneous, intravenous, intraperitoneal, intramuscular, intraarterial, intralesional or intra-articular routes, topically, inhaled or by sustained or delayed release. The pharmaceutical compositions or lyophilized formulations of the present invention may be diluted with a suitable diluent to a suitable concentration prior to administration to provide the optimal desired response (e.g., therapeutic response).
The invention also provides a method of treating a disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention. The invention also provides the use of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention in the manufacture of a medicament for treating a disease in a subject.
The invention also provides a method of treating an autoimmune disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention. The invention also provides the use of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention in the manufacture of a medicament for treating an autoimmune disease in a subject. Non-limiting examples of the autoimmune diseases include psoriasis (Ps), genital psoriasis (GenPs), pruritis, plaque psoriasis, hidradenitis Suppurativa (HS), palmoplantar pustulosis (PPP), psoriatic Arthritis (PA), axial spondylitis, ankylosing Spondylitis (AS), inflammatory bowel disease, multiple sclerosis, non-radiological axial spondylitis, rheumatoid arthritis, multiple Myeloma (MM), and the like.
The pharmaceutical composition of the invention can effectively inhibit aggregation and deamidation of antibodies, and a stable injection composition is obtained. The pharmaceutical composition of the invention has a protective effect on oxidative degradation of proteins, so that the proteins can be stably stored in a glass container.
Detailed Description
For a better understanding of the invention, some terms will be defined. Unless defined otherwise herein, all other techniques and terms used herein are intended to be within the meaning commonly understood by one of ordinary skill in the art to which the invention pertains.
Definition of the definition
"Buffer" refers to a pharmaceutically acceptable substance or mixture of substances capable of maintaining the pH of a pharmaceutical composition to a desired pH range. Examples of buffers suitable for use in the pharmaceutical compositions of the present invention include acetate buffers or histidine salt buffers.
An "acetate buffer" is a buffer comprising acetate ions, for example a buffer comprising acetic acid and/or acetate salts, wherein acetic acid comprises acetic acid and/or its hydrates, and acetate salts comprises acetate salts and/or its hydrates. Examples of acetate buffers include, but are not limited to, potassium acetate buffer, ammonium acetate buffer or sodium acetate buffer, acetic acid-sodium acetate buffer, with a preferred acetate buffer being acetic acid-sodium acetate buffer. The acetic acid-sodium acetate buffer comprises acetic acid and sodium acetate, wherein the acetic acid comprises acetic acid and/or a hydrate thereof and the sodium acetate comprises sodium acetate and/or a hydrate thereof. In one specific example, the acetic acid-sodium acetate buffer may be formulated from sodium acetate trihydrate and acetic acid (e.g., 20 mmol/L acetic acid-sodium acetate buffer (pH 5.5) may be formulated from about 2.34 g/L sodium acetate trihydrate and about 0.47 g/L acetic acid (36%). In another specific example, the acetic acid-sodium acetate buffer may be formulated from anhydrous sodium acetate and acetic acid (e.g., 20 mmol/L acetic acid-sodium acetate buffer (pH 5.5) may be formulated from about 1.41 g/L anhydrous sodium acetate and about 0.17 g/L acetic acid).
A "histidine salt buffer" is a buffer comprising histidine ions, e.g. a buffer comprising histidine and/or a histidine salt, wherein histidine comprises histidine and/or a hydrate thereof, and histidine salt comprises histidine salt and/or a hydrate thereof. Examples of histidine salt buffers include histidine-acetic acid buffers or histidine-histidine hydrochloride buffers, in one specific example, histidine-histidine hydrochloride buffers are formulated from histidine and histidine hydrochloride monohydrate (C 6H9N3O2·HCl·H2 O).
"Stabilizer" refers to a pharmaceutically acceptable substance that helps maintain the structural integrity of the active ingredient (e.g., antibody) in the pharmaceutical composition, particularly during freezing, lyophilization, storage, and/or transportation (especially when exposed to stress). In the present invention, the stabilizer may also be used as a viscosity reducer and/or an isotonic agent, etc.
In this document, the terms "comprises," "comprising," and "includes" are to be construed as including the stated step or element or group of steps or elements, but not excluding any other step or element or group of steps or elements, unless the context dictates otherwise.
In the invention, the technical characteristics described in an open mode comprise a closed technical scheme composed of the listed characteristics and also comprise an open technical scheme comprising the listed characteristics.
"IL-17A" refers to interleukin 17A or a cytokine of the IL-17 cytokine family (also known as cytotoxic T-lymphocyte-associated antigen 8 ("CTLA 8")). IL-17A cytokines exist as homodimeric complexes (e.g., IL-17A/A) or as heterodimeric complexes (e.g., IL-17A/F) complexed with another IL17 cytokine family member, e.g., IL-17F. IL-17A cytokines are thought to be produced primarily by effector T helper (Th 17) cells, and have been shown to induce secretion of pro-inflammatory cytokines such as IL-6, IL-8, IL-1 and TNF. Homodimeric complex forms of IL17A/a have been shown to play a role in diseases such as psoriasis and psoriatic arthritis (both immune related diseases are associated with T cell dysregulation). An anti-IL-17A antibody or antigen-binding fragment thereof in the present invention is an antibody that specifically binds to and antagonizes human IL-17A by virtue of its specificity for an A subunit (e.g., one or both of the A subunits of IL-17A/F or IL-17A/A).
"IL-17A" includes variants, subtypes, homologs, orthologs, and paralogs. For example, in certain instances, antibodies specific for human IL-17A protein may cross-react with IL-17A protein from a species other than human (e.g., monkey). In other embodiments, antibodies specific for human IL-17A protein may be fully specific for human IL-17A protein and do not cross-react with other species or other types of proteins, or may cross-react with IL-17A from some other species but not all other species.
"Subject" includes any human or non-human animal. The term "non-human animal" includes all vertebrates, such as mammals and non-mammals, preferably mammals, such as non-human primates, sheep, dogs, cats, cattle and horses.
"Treatment" means all processes in which there may be complete elimination, slowing or delaying, reduction in severity or frequency (e.g., bursts or episodes) of the disease and/or its symptoms, interruption or cessation of its progression, but not necessarily complete elimination of all disease symptoms. Treatment comprises administration of an aqueous pharmaceutical formulation of the invention for treating a disease in a human that would benefit from at least one of the processes listed above, comprising: inhibiting the further progression of disease symptoms and effects, i.e., arresting the development thereof; remitting the disease, i.e., causing elimination or regression of the disease, disease symptoms, or complications thereof; and preventing or reducing the frequency of onset or outbreak of disease.
"Therapeutically effective amount" refers to an amount of an antibody of the invention that is sufficient to prevent or ameliorate symptoms associated with a disease or disorder (e.g., cancer), and/or to reduce the severity of a disease or disorder. It will be appreciated that a therapeutically effective amount will be relevant to the disease being treated, wherein one skilled in the art can readily ascertain the actual effective amount.
"Identity" refers to sequence similarity between two polynucleotide sequences or between two polypeptides. "percent (%) identity" of amino acid sequences refers to the percentage of amino acid residues in an aligned sequence that are identical to the amino acid residues of a particular amino acid sequence shown herein, after aligning the aligned sequence to the particular amino acid sequence shown herein and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and without regard to any conservative substitutions as part of the sequence identity. Amino acid sequence alignment for identity can be performed in a variety of ways within the skill in the art, such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. One skilled in the art can determine the appropriate parameters for aligning sequences, including any algorithm needed to obtain the maximum alignment over the entire length of the compared sequences.
By "administering" is meant physically introducing a therapeutic agent into a subject using any of a variety of methods and delivery systems known to those of skill in the art.
Pharmaceutical composition
The invention provides a pharmaceutical composition, wherein the pharmaceutical composition comprises: an anti-IL-17A antibody or antigen-binding fragment thereof, a buffer, a stabilizer, and a surfactant.
In some embodiments, the pharmaceutical composition contains the anti-IL-17A antibody or antigen-binding fragment thereof at a concentration of 20-200 mg/mL, 50-150 mg/mL, 60-120 mg/mL, or 70-90 mg/mL. In some embodiments, the concentration of anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition includes, but is not limited to ：20 mg/mL、30 mg/mL、40 mg/mL、50 mg/mL、60 mg/mL、70 mg/mL、71 mg/mL、72 mg/mL、73 mg/mL、74 mg/mL、75 mg/mL、76 mg/mL、77 mg/mL、78 mg/mL、79 mg/mL、80 mg/mL、81 mg/mL、82 mg/mL、83 mg/mL、84 mg/mL、85 mg/mL、86 mg/mL、87 mg/mL、88 mg/mL、89 mg/mL、90 mg/mL、95 mg/mL、100 mg/mL、110 mg/mL、120 mg/mL、150 mg/mL、180 mg/mL or 200 mg/mL. In some embodiments, the concentration of the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition is 80 mg/mL.
In some embodiments, the buffer in the pharmaceutical composition may be selected from phosphate buffer, tris buffer, citrate buffer, carbonate buffer, acetate buffer, or histidine salt buffer. In some embodiments, examples of the acetate buffer include sodium acetate buffer, potassium acetate buffer, or sodium acetate-acetate buffer, and examples of the histidine salt buffer include histidine-histidine hydrochloride buffer or histidine-acetate buffer.
In some embodiments, the concentration of buffer in the pharmaceutical composition is 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L. In some embodiments, the concentration of buffer in the pharmaceutical composition includes, but is not limited to ：1 mmol/L、2 mmol/L、3 mmol/L、4 mmol/L、5 mmol/L、6 mmol/L、7 mmol/L、8 mmol/L、9 mmol/L、10 mmol/L、11 mmol/L、12 mmol/L、13 mmol/L、14 mmol/L、15 mmol/L、16 mmol/L、17 mmol/L、18 mmol/L、19 mmol/L、20 mmol/L、21 mmol/L、22 mmol/L、23 mmol/L、24 mmol/L、25 mmol/L、26 mmol/L、27 mmol/L、29 mmol/L、30 mmol/L、40 mmol/L or 50 mmol/L. In some embodiments, the concentration of buffer in the pharmaceutical composition is 20 mmol/L.
In some embodiments, the buffer in the pharmaceutical composition is 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L acetate buffer. In some embodiments, the buffer in the pharmaceutical composition is 1 mmol/L、2 mmol/L、3 mmol/L、4 mmol/L、5 mmol/L、6 mmol/L、7 mmol/L、8 mmol/L、9 mmol/L、10 mmol/L、11 mmol/L、12 mmol/L、13 mmol/L、14 mmol/L、15 mmol/L、16 mmol/L、17 mmol/L、18 mmol/L、19 mmol/L、20 mmol/L、21 mmol/L、22 mmol/L、23 mmol/L、24 mmol/L、25 mmol/L、26 mmol/L、27 mmol/L、29 mmol/L、30 mmol/L、40 mmol/L or 50 mmol/L acetate buffer. In some embodiments, the buffer in the pharmaceutical composition is 20 mmol/L acetate buffer.
In some embodiments, the buffer in the pharmaceutical composition is 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L of acetic acid-sodium acetate buffer. In some embodiments, the buffer in the pharmaceutical composition is 1 mmol/L、2 mmol/L、3 mmol/L、4 mmol/L、5 mmol/L、6 mmol/L、7 mmol/L、8 mmol/L、9 mmol/L、10 mmol/L、11 mmol/L、12 mmol/L、13 mmol/L、14 mmol/L、15 mmol/L、16 mmol/L、17 mmol/L、18 mmol/L、19 mmol/L、20 mmol/L、21 mmol/L、22 mmol/L、23 mmol/L、24 mmol/L、25 mmol/L、26 mmol/L、27 mmol/L、29 mmol/L、30 mmol/L、40 mmol/L or 50 mmol/L of acetic acid-sodium acetate buffer. In some embodiments, the buffer in the pharmaceutical composition is 20 mmol/L acetic acid-sodium acetate buffer.
In some embodiments, the buffer in the pharmaceutical composition is a histidine salt buffer of 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L. In some embodiments, the buffer in the pharmaceutical composition is a histidine salt buffer at a concentration including, but not limited to ：1 mmol/L、2 mmol/L、3 mmol/L、4 mmol/L、5 mmol/L、6 mmol/L、7 mmol/L、8 mmol/L、9 mmol/L、10 mmol/L、11 mmol/L、12 mmol/L、13 mmol/L、14 mmol/L、15 mmol/L、16 mmol/L、17 mmol/L、18 mmol/L、19 mmol/L、20 mmol/L、21 mmol/L、22 mmol/L、23 mmol/L、24 mmol/L、25 mmol/L、26 mmol/L、27 mmol/L、29 mmol/L、30 mmol/L、40 mmol/L or 50 mmol/L. In some embodiments, the buffer in the pharmaceutical composition is 20 mmol/L histidine salt buffer.
In some embodiments, the buffer in the pharmaceutical composition is a histidine-histidine hydrochloride buffer of 1-50 mmol/L, 5-30 mmol/L, 10-25 mmol/L, or 15-25 mmol/L. In some embodiments, the buffer in the pharmaceutical composition is histidine-histidine hydrochloride buffer at a concentration including, but not limited to ：1 mmol/L、2 mmol/L、3 mmol/L、4 mmol/L、5 mmol/L、6 mmol/L、7 mmol/L、8 mmol/L、9 mmol/L、10 mmol/L、11 mmol/L、12 mmol/L、13 mmol/L、14 mmol/L、15 mmol/L、16 mmol/L、17 mmol/L、18 mmol/L、19 mmol/L、20 mmol/L、21 mmol/L、22 mmol/L、23 mmol/L、24 mmol/L、25 mmol/L、26 mmol/L、27 mmol/L、29 mmol/L、30 mmol/L、40 mmol/L or 50 mmol/L. In some embodiments, the buffer in the pharmaceutical composition is 20 mmol/L histidine-histidine hydrochloride buffer.
In some embodiments, the stabilizing agent in the pharmaceutical composition comprises a sugar alcohol (e.g., mannitol, sorbitol), a disaccharide (e.g., trehalose, sucrose, maltose, lactose), a monosaccharide (e.g., dextrose (D-glucose)), an amino acid (e.g., lysine, glycine, proline, arginine, or a pharmaceutically acceptable salt thereof), or a salt (e.g., sodium chloride). In some embodiments, the stabilizing agent in the pharmaceutical composition comprises sucrose.
In some embodiments, the concentration of the stabilizing agent in the pharmaceutical composition is 1-110 mg/mL, 40-110 mg/mL, 50-80 mg/mL, or 70-80 mg/mL. In some embodiments, the stabilizer in the pharmaceutical composition is at a concentration including, but not limited to ：5 mg/mL、10 mg/mL、15 mg/mL、20 mg/mL、25 mg/mL、30 mg/mL、35 mg/mL、40 mg/mL、45 mg/mL、50 mg/mL、60 mg/mL、61 mg/mL、62 mg/mL、63 mg/mL、64 mg/mL、65 mg/mL、66 mg/mL、67 mg/mL、68 mg/mL、69 mg/mL、70 mg/mL、71 mg/mL、72 mg/mL、73 mg/mL、74 mg/mL、75 mg/mL、76 mg/mL、77 mg/mL、78 mg/mL、79 mg/mL、80 mg/mL、81 mg/mL、82 mg/mL、83 mg/mL、84 mg/mL、85 mg/mL、86 mg/mL、87 mg/mL、88 mg/mL、89 mg/mL、90 mg/mL、91 mg/mL、92 mg/mL、93 mg/mL、94 mg/mL、95 mg/mL、96 mg/mL、97 mg/mL、98 mg/mL、99 mg/mL、100 mg/mL、 or 110 mg/mL. In some embodiments, the concentration of the stabilizer in the pharmaceutical composition is 80 mg/mL.
In some embodiments, the stabilizer in the pharmaceutical composition is 1-110 mg/mL, 40-110 mg/mL, 50-80 mg/mL, or 70-80 mg/mL sucrose. In some embodiments, the stabilizer in the pharmaceutical composition is sucrose at a concentration including, but not limited to ：5 mg/mL、10 mg/mL、15 mg/mL、20 mg/mL、25 mg/mL、30 mg/mL、35 mg/mL、40 mg/mL、45 mg/mL、50 mg/mL、60 mg/mL、61 mg/mL、62 mg/mL、63 mg/mL、64 mg/mL、65 mg/mL、66 mg/mL、67 mg/mL、68 mg/mL、69 mg/mL、70 mg/mL、71 mg/mL、72 mg/mL、73 mg/mL、74 mg/mL、75 mg/mL、76 mg/mL、77 mg/mL、78 mg/mL、79 mg/mL、80 mg/mL、81 mg/mL、82 mg/mL、83 mg/mL、84 mg/mL、85 mg/mL、86 mg/mL、87 mg/mL、88 mg/mL、89 mg/mL、90 mg/mL、91 mg/mL、92 mg/mL、93 mg/mL、94 mg/mL、95 mg/mL、96 mg/mL、97 mg/mL、98 mg/mL、99 mg/mL、100 mg/mL、 or 110 mg/mL. In some embodiments, the stabilizer in the pharmaceutical composition is 80 mg/mL sucrose.
In some embodiments, the surfactant in the pharmaceutical composition is selected from a polysorbate (e.g., polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 81, or polysorbate 85), a poloxamer (e.g., poloxamer 181, poloxamer 188, or poloxamer 407), a polyethylene glycol, or a polyhydroxy body, and the like. In some embodiments, the surfactant in the pharmaceutical composition is polysorbate 80.
In some embodiments, the concentration of surfactant in the pharmaceutical composition is 0.01-2 mg/mL, 0.05-1 mg/mL, 0.2-0.6 mg/mL, or 0.2-0.4 mg/mL. In some embodiments, the concentration of surfactant in the pharmaceutical composition includes, but is not limited to ：0.06 mg/mL、0.08 mg/mL、0.1 mg/mL、0.2 mg/mL、0.3 mg/mL、0.4 mg/mL、0.5 mg/mL、0.6 mg/mL、0.7 mg/mL、0.8 mg/mL、0.9 mg/mL or 1 mg/mL. In some embodiments, the concentration of surfactant in the pharmaceutical composition is 0.3 mg/mL.
In some embodiments, the surfactant in the pharmaceutical composition is polysorbate 80 at 0.01-2 mg/mL, 0.05-1 mg/mL, 0.2-0.6 mg/mL, or 0.2-0.4 mg/mL. In some embodiments, the surfactant in the pharmaceutical composition is polysorbate 80 at a concentration including, but not limited to ：0.06 mg/mL、0.08 mg/mL、0.1 mg/mL、0.2 mg/mL、0.3 mg/mL、0.4 mg/mL、0.5 mg/mL、0.6 mg/mL、0.7 mg/mL、0.8 mg/mL、0.9 mg/mL or 1 mg/mL. In some embodiments, the surfactant in the pharmaceutical composition is polysorbate 80 at 0.3 mg/mL.
In some embodiments, the pharmaceutical composition has a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0. In some embodiments, the pH of the pharmaceutical composition includes, but is not limited to: 5. 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.5, 6.3, 6.4 or 6.5. In some embodiments, the pharmaceutical composition has a pH of about 5.0. In some embodiments, the pharmaceutical composition has a pH of about 5.5. In some embodiments, the pharmaceutical composition has a pH of about 6.0. In some embodiments, the pharmaceutical composition has a pH of about 6.5.
In some embodiments, the pharmaceutical composition comprises: anti-IL-17A antibodies or antigen binding fragments thereof, acetate buffer, sucrose and polysorbate 80.
In some embodiments, the pharmaceutical composition comprises: anti-IL-17A antibodies or antigen binding fragments thereof, histidine salt buffer, sucrose and polysorbate 80.
In some embodiments, the pharmaceutical composition comprises: 20-200 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 1-50 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 1-110 mg/mL of a stabilizing agent (e.g., sucrose), and 0.01-2 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: 50-150 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 5-30 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 40-110 mg/mL of a stabilizing agent (e.g., sucrose), and 0.05-1 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: 60-120 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 10-25 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 50-80 mg/mL of a stabilizing agent (e.g., sucrose), and 0.2-0.6 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: 70-90 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof, 15-25 mmol/L buffer (e.g., acetate buffer or histidine salt buffer), 70-80 mg/mL of a stabilizing agent (e.g., sucrose), and 0.2-0.4 mg/mL of a surfactant (e.g., polysorbate 80), the pharmaceutical composition having a pH of 4.0-7.0, 5.0-6.5, 5.0-6.0, or 5.5-6.0.
In some embodiments, the pharmaceutical composition comprises: an anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of acetic acid-sodium acetate buffer, 80 mg/mL of sucrose, and 0.3 mg/mL of polysorbate 80, wherein the concentration of the anti-IL-17A antibody or antigen-binding fragment thereof is 60 mg/mL, 65 mg/mL, 70 mg/mL, 75 mg/mL, 80 mg/mL, or 85mg/mL; the pH of the pharmaceutical composition is 5.0-5.5.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of anti-IL-17A antibody or antigen-binding fragment thereof, acetic acid-sodium acetate buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, wherein the concentration of the acetic acid-sodium acetate buffer is 10 mmol/L, 15 mmol/L, 20 mmol/L, or 25 mmol/L; the pH of the pharmaceutical composition is 5.0-5.5.
In some embodiments, the pharmaceutical composition comprises: 80mg/mL of anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of acetic acid-sodium acetate buffer, sucrose, and 0.3: 0.3 mg/mL of polysorbate 80, wherein the sucrose is at a concentration of 70mg/mL, 75: 75 mg/mL, 80mg/mL, 85mg/mL, 90mg/mL, or 95mg/mL; the pH of the pharmaceutical composition is 5.0-5.5.
In some embodiments, the pharmaceutical composition comprises: 80mg/mL of anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of acetic acid-sodium acetate buffer, 80mg/mL of sucrose, and polysorbate 80, wherein the concentration of polysorbate 80 is 0.1 mg/mL, 0.2 mg/mL, or 0.3 mg/mL; the pH of the pharmaceutical composition is 5.0-5.5.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of acetic acid-sodium acetate buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pharmaceutical composition having a pH of 5.5.
In some embodiments, the pharmaceutical composition comprises: an anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L histidine-hcl histidine buffer, 80 mg/mL sucrose, and 0.3 mg/mL polysorbate 80, wherein the concentration of the anti-IL-17A antibody or antigen-binding fragment thereof is 60 mg/mL, 65 mg/mL, 70 mg/mL, 75 mg/mL, 80 mg/mL, or 85mg/mL; the pH of the pharmaceutical composition is 5.0-5.5.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of anti-IL-17A antibody or antigen-binding fragment thereof, histidine-histidine hydrochloride buffer, 80 mg/mL sucrose, and 0.3 mg/mL polysorbate 80, wherein the concentration of histidine-histidine hydrochloride buffer is 10 mmol/L, 15 mmol/L, 20 mmol/L, or 25 mmol/L; the pH of the pharmaceutical composition is 5.0-6.5.
In some embodiments, the pharmaceutical composition comprises: 80mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L histidine-hcl histidine buffer, sucrose, and 0.3 mg/mL polysorbate 80, wherein the sucrose concentration is 70mg/mL, 75 mg/mL, 80mg/mL, 85mg/mL, 90mg/mL, or 95mg/mL; the pH of the pharmaceutical composition is 5.0-6.5.
In some embodiments, the pharmaceutical composition comprises: 80mg/mL of anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L histidine-hcl histidine buffer, 80mg/mL sucrose, and polysorbate 80, wherein the concentration of polysorbate 80 is 0.1 mg/mL, 0.2 mg/mL, or 0.3 mg/mL; the pH of the pharmaceutical composition is 5.0-6.5.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 5.0.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 5.5.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 6.0.
In some embodiments, the pharmaceutical composition comprises: 80 mg/mL of the anti-IL-17A antibody or antigen-binding fragment thereof, 20 mmol/L of histidine-HCl buffer, 80 mg/mL of sucrose, and 0.3. 0.3 mg/mL of polysorbate 80, the pH of the pharmaceutical composition is 6.5.
Anti-IL-17A antibodies or antigen binding fragments thereof
In some embodiments, an anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region comprising heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3, wherein heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3 comprise amino acid sequences that are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequences set forth in SEQ ID NOs 1, 2, and 3, respectively. Wherein, the amino acid sequence of SEQ ID NO 1-3 is:
GYSFTDYHIH (SEQ ID NO: 1)；
VINPMYGTTDYNQRFKG (SEQ ID NO: 2)；
YDYFTGTGVY (SEQ ID NO: 3)。
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth in SEQ ID NO. 7. Wherein, the amino acid sequence of SEQ ID NO. 7 is:
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTDYHIHWVRQAPGQGLEWMGVINPMYGTTDYNQRFKGRVTITADESTSTAYMELSSLRSEDTAVYYCARYDYFTGTGVYWGQGTLVTVSS (SEQ ID NO: 7).
in some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain comprising an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence set forth in SEQ ID No. 9. Wherein, the amino acid sequence of SEQ ID NO. 9 is:
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTDYHIHWVRQAPGQGLEWMGVINPMYGTTDYNQRFKGRVTITADESTSTAYMELSSLRSEDTAVYYCARYDYFTGTGVYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 9).
In some embodiments, an anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a light chain variable region comprising light chain CDR1, light chain CDR2, and light chain CDR3, wherein light chain CDR1, light chain CDR2, and light chain CDR3 comprise amino acid sequences that are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequences set forth in SEQ ID NOs 4, 5, and 6, respectively. Wherein, the amino acid sequence of SEQ ID NO. 4-6 is:
RSSRSLVHSRGNTYLH (SEQ ID NO: 4)；
KVSNRFI (SEQ ID NO: 5)；
SQSTHLPFT (SEQ ID NO: 6)。
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a light chain variable region comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth in SEQ ID NO. 8. Wherein, the amino acid sequence of SEQ ID NO. 8 is:
DIVMTQTPLSLSVTPGQPASISCRSSRSLVHSRGNTYLHWYLQKPGQSPQLLIYKVSNRFIGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHLPFTFGQGTKLEIK (SEQ ID NO: 8).
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a light chain comprising an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence set forth in SEQ ID No. 10. Wherein, the amino acid sequence of SEQ ID NO. 10 is:
DIVMTQTPLSLSVTPGQPASISCRSSRSLVHSRGNTYLHWYLQKPGQSPQLLIYKVSNRFIGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHLPFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 10).
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region and a light chain variable region, wherein heavy chain CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2, and light chain CDR3 comprise amino acid sequences that are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences set forth in SEQ ID NOs 1, 2, 3, 4, 5, and 6, respectively.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain variable region and a light chain variable region comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to an amino acid sequence set forth in SEQ ID NOs 7 and 8, respectively.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition comprises a heavy chain and a light chain comprising an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth in SEQ ID NOs 9 and 10, respectively.
In some embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition may be a full length antibody, e.g., an IgG1, igG2, or IgG4 isotype full length antibody, preferably an IgG4 isotype full length antibody. In other embodiments, the anti-IL-17A antibody or antigen-binding fragment thereof in the pharmaceutical composition may be a single chain variable region (scFv) antibody, or an antibody fragment, such as a Fab or F (ab') 2 fragment.
Preparation method
The invention also provides a preparation method of the pharmaceutical composition, which comprises the following steps: the anti-IL-17A antibody or antigen-binding fragment thereof, a buffer, a stabilizer, and a surfactant are mixed to prepare a pharmaceutical composition.
In some embodiments, the method of preparing further comprises the step of sterilizing the mixture obtained by mixing. It will be appreciated that the invention is not limited in particular to the manner in which the bacteria are removed, and that membrane filtration may be used, but is not limited thereto.
The manner, order, etc. of mixing the components in the preparation process are not particularly limited.
In one embodiment, the preparation method of the present invention comprises: mixing the anti-IL-17A antibody or antigen-binding fragment thereof, a buffer and a stabilizer to prepare mixture 1; and mixing the mixture 1 and the surfactant to prepare a pharmaceutical composition.
Optionally, the step of preparing said mixture 1 comprises: the anti-IL-17A antibody or antigen-binding fragment thereof is replaced by ultrafiltration into the buffer and stabilizer, optionally concentrated, to prepare the mixture 1.
It will be appreciated that the method of manufacture of the present invention further comprises the step of dispensing (e.g. into penicillin bottles) the pharmaceutical composition prepared.
Freeze-dried preparation
The invention also provides a freeze-dried preparation, which is obtained by freeze-drying the pharmaceutical composition. In some embodiments, the freeze-drying is performed according to methods well known in the art, including but not limited to the steps of prefreezing, primary drying, and secondary drying. Those skilled in the art will appreciate that any method of removing water from the pharmaceutical compositions of the present invention is suitable for use in the present invention.
The invention also provides a freeze-dried preparation which can be reconstituted to form the pharmaceutical composition of the invention. In some embodiments, the solution used for reconstitution includes, but is not limited to, water for injection, sodium chloride injection, ringer's solution, or dextrose injection.
Article of manufacture
The invention also provides an article of manufacture comprising the pharmaceutical composition or lyophilized formulation of the invention. In some embodiments, the articles of the invention comprise a container containing a pharmaceutical composition or lyophilized formulation of the invention.
Use of the same
The invention also provides a method of treating a disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention. The invention also provides the use of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention in the manufacture of a medicament for treating a disease in a subject.
The invention also provides a method of treating an autoimmune disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention. The invention also provides the use of a pharmaceutical composition, lyophilized formulation or article of manufacture of the invention in the manufacture of a medicament for treating an autoimmune disease in a subject. Non-limiting examples of the autoimmune diseases include Ps, genPs, pruritis, plaque psoriasis, HS, PPP, PA, axial spondyloarthritis, AS, inflammatory bowel disease, multiple sclerosis, non-radiological axial spondyloarthritis, rheumatoid arthritis, MM, and the like.
The pharmaceutical compositions, lyophilized formulations or articles of the present invention may be administered according to methods known in the art. In some embodiments, the lyophilized formulation requires reconstitution prior to administration to obtain a reconstituted solution of the lyophilized formulation. In some embodiments, reconstitution may be performed with water for injection, sodium chloride injection, ringer's solution, or dextrose injection.
In some embodiments, the pharmaceutical compositions, lyophilized formulations or articles of the invention are suitable for parenteral administration. In some embodiments, the pharmaceutical compositions, lyophilized formulations and articles of the invention are suitable for intravenous, intramuscular, intraperitoneal, subcutaneous, epidermal, spinal, intralesional injection or infusion. In some embodiments, the pharmaceutical compositions, lyophilized formulations and articles of the present invention are suitable for topical administration, inhalation, oral administration or administration by sustained release or extended release delivery systems. In some embodiments, the pharmaceutical compositions, lyophilized formulations, reconstituted solutions of lyophilized formulations of the present invention may be diluted with a suitable diluent prior to administration. In some embodiments, dilution may be performed with water for injection, sodium chloride injection, ringer's solution, or dextrose injection.
Embodiments of the present invention will be described in detail with reference to examples. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples, in which specific conditions are not noted, are preferably referred to the guidelines given in the present invention, and may be according to the experimental manual or conventional conditions in the art, the conditions suggested by the manufacturer, or the experimental methods known in the art. In the examples which follow, reference is made to measurement parameters of the constituents of the raw materials, there being possible, unless otherwise specified, minor deviations in the accuracy of the weighing. Temperature and time parameters are involved, allowing acceptable deviations from instrument testing accuracy or operational accuracy.
Example 1: pharmaceutical composition containing anti-IL-17A antibody
Pharmaceutical compositions containing anti-IL-17A antibodies, buffers, stabilizers and surfactants were prepared according to table 1, the preparation steps comprising: the anti-IL-17A antibody expressed and purified in the cells previously was replaced in a buffer by ultrafiltration, concentrated after completion of replacement, then a stabilizer and a surfactant were added according to Table 1, the final concentration of the anti-IL-17A antibody was 80 mg/mL, and after uniform mixing, the pH was adjusted to the pH specified in Table 1 with hydrochloric acid or sodium hydroxide, sterilized by filtration through a 0.22 μm filter membrane, and packaged in penicillin bottles, capped with celecoxib.
TABLE 1 composition of pharmaceutical composition
* The anti-IL-17A antibody comprises the heavy chain of SEQ ID NO. 9 and the light chain of SEQ ID NO. 10.
Example 2: stability Experimental design of pharmaceutical composition containing anti-IL-17A antibody
Stability experimental design a multivariate procedure was used to examine the physical and chemical stability of pharmaceutical compositions containing anti-IL-17A antibodies. Each variable was studied at five levels and the pharmaceutical compositions containing IL-17A antibodies were formulated as described in example 1 and the formulations described in table 1. Pharmaceutical compositions F1, F2, F3, F4 and F5 were stored at 2-8 ℃ or 40 ℃ and a relative humidity of 75% (40 ℃/75% rh), and physical and chemical stability was measured at 0 days and 5 weeks to evaluate the long-term stability of F1, F2, F3, F4 and F5 at 2-8 ℃ and 40 ℃/75% rh high temperature stability. The examination index and time point are shown in table 2.
TABLE 2 sample retention investigation experiment design
A=protein melting temperature (Tm), protein aggregation temperature (Tagg);
b = visual appearance and foreign matter;
X = size exclusion high performance liquid chromatography (SEC-HPLC), weak cation chromatography (CEX-HPLC), sodium dodecyl sulfate capillary electrophoresis (reduced CE-SDS), relative binding activity;
Y = pH;
Z = osmolality, protein content.
Example 3: tm and Tagg of pharmaceutical compositions
The pharmaceutical composition configured according to example 1 was tested for protein melting temperature (Tm) and protein aggregation temperature (Tagg). The Tm and Tagg results of the pharmaceutical compositions F1, F2, F3, F4 and F5 are shown in table 3. The results show that: the Tm of F1 is the lowest, and the Tm values of F2, F3, F4 and F5 are equivalent. The Tagg value of F1 is lowest, the Tagg values of F2 and F5 are higher, and the Tagg value of F4 is highest.
TABLE 3 Tm and Tagg for pharmaceutical compositions at day 3.0
Example 4: stability of pharmaceutical composition stored at 2-8deg.C
The pharmaceutical composition configured according to example 1 was subjected to stability investigation according to the protocol designed in example 2. The pharmaceutical compositions F1, F2, F3, F4 and F5 were stored at 2-8deg.C for 5 weeks, and were left as such for 0 day and 5 weeks, and the stability of the pharmaceutical compositions was examined according to the index of Table 2, and the specific index and data are shown in tables 4-5.
TABLE 4 detection results I at 2-8℃
Note that: "-" indicates no test.
TABLE 5 detection results II at 2-8deg.C
The results show that: f1, F2, F3, F4 and F5 are colorless micro-emulsion liquid when stored for 0 day and 5 weeks at 2-8deg.C; the pharmaceutical composition has no significant changes or differences in anti-IL-17A antibody concentration, pH and osmolality after 5 weeks of storage at 2-8 ℃ compared to the starting time point (day 0); the results of SEC-HPLC showed no significant change in immunoglobulin monomer content at day 0 and week 5 for the pharmaceutical composition containing histidine-histidine hydrochloride buffer (F1, F2, F3 and F4), the most polymeric impurities and the most polymeric impurities increase for the pharmaceutical composition containing sodium acetate-acetate buffer (F5) compared to the pharmaceutical composition containing histidine-histidine hydrochloride buffer (F1, F2, F3 and F4); the main peak, the acid peak and the alkaline peak of all the pharmaceutical compositions have no obvious change in the storage process measured by CEX-HPLC; all the pharmaceutical compositions showed no significant change in immunoglobulin monomer content during storage as determined by the reduction type CE-SDS; with respect to the relative activity of the antibodies, the relative activity of the pharmaceutical composition (F5) containing the acetic acid-sodium acetate buffer was the lowest (84%) after 5 weeks of storage at 2-8 ℃, the relative activity of the pharmaceutical compositions containing the histidine-hydrochloride buffers (F1, F2, F3 and F4) was higher than 85% after 5 weeks of storage of F3 (pH 6.0) and F4 (pH 6.5), the relative activity of the pharmaceutical compositions after 5 weeks of storage of F1 (pH 5.0) and F2 (pH 5.5) was higher than 90%, and the relative activity of the pharmaceutical compositions after 5 weeks of storage of F2 (pH 5.5) was the highest.
Example 5: stability of pharmaceutical composition stored under 40 ℃/75% RH conditions
The pharmaceutical composition configured according to example 1 was subjected to stability investigation according to the protocol designed in example 2. Pharmaceutical compositions F1, F2, F3, F4 and F5 were stored at 40 ℃/75% rh for 5 weeks, left as such for 0 days and 5 weeks, and the stability of the pharmaceutical compositions was examined according to the indices of table 2, with specific indices and data shown in tables 6-7.
TABLE 6 detection results I at 40 ℃/75% RH
Note that: "-" indicates no test.
TABLE 7 detection results II at 40 ℃/75% RH
The results show that: f1, F2, F3, F4 and F5 all appeared as colorless microemulsion liquids when stored for 0 days and 5 weeks at 40 ℃/75% rh; the pharmaceutical composition has no significant changes or differences in anti-IL-17A antibody concentration, pH and osmolality after 5 weeks of storage at 2-8 ℃ compared to the starting time point (day 0); the results of SEC-HPLC showed that the immunoglobulin monomer content of all the pharmaceutical compositions decreased slightly during storage, the pharmaceutical composition containing the acetic acid-sodium acetate buffer (F5) had the most polymeric impurities and the polymeric impurities increased the most compared to the pharmaceutical composition containing the histidine-hcl buffer (F1, F2, F3 and F4); the relative areas of main peaks of all the pharmaceutical compositions are reduced, the acid peak is increased, the alkaline peak is reduced, and the relative areas of main peaks of F3, F4 and F5 are reduced by more than 20% in the storage process measured by CEX-HPLC; all the pharmaceutical compositions showed no significant change in immunoglobulin monomer content during storage as determined by the reduction type CE-SDS; in terms of antibody relative activity, the antibody relative activity of all pharmaceutical compositions decreased slightly during storage, at 5 weeks, the antibody relative activity of both F1 and F2 was greater than 90%, and the antibody relative activity of F5 was the lowest.
The foregoing description of the embodiments and examples illustrates the principles of the invention and its effectiveness, and is not intended to limit the invention in any way or in essence, but it should be noted that modifications and additions may be made to the person skilled in the art without departing from the scope of the invention. Equivalent embodiments of the present invention will be apparent to those skilled in the art having the benefit of the teachings of this disclosure, and modifications, to those skilled in the art, and the invention; it should also be understood that, based on the technical solutions provided by the present invention, those skilled in the art obtain technical solutions through logical analysis, reasoning or limited experiments, which are all within the scope of protection of the appended claims. The scope of the patent of the invention should therefore be determined with reference to the appended claims, which are to be construed as in accordance with the doctrines of claim interpretation.

Claims (10)

1. A pharmaceutical composition, characterized in that it comprises:
(a) 70-90 mg/mL of an anti-IL-17A antibody or antigen-binding fragment thereof,
(B) 15-25 mmol/L of buffer,
(C) 70-80 mg/mL sucrose, and
(D) 0.2-0.4 mg/mL polysorbate 80,
Wherein the anti-IL-17A antibody or antigen binding fragment thereof comprises HCDR1 shown in SEQ ID NO. 1, HCDR2 shown in SEQ ID NO. 2, HCDR3 shown in SEQ ID NO. 3, LCDR1 shown in SEQ ID NO.4, LCDR2 shown in SEQ ID NO. 5 and LCDR3 shown in SEQ ID NO.6, and the pH of the pharmaceutical composition is 5.0-6.5.
2. The pharmaceutical composition of claim 1, wherein the concentration of the anti-IL-17A antibody or antigen-binding fragment thereof is 80 mg/mL.
3. The pharmaceutical composition of claim 1, wherein the buffer is a histidine salt buffer or an acetate buffer at a concentration of 20 mmol/L.
4. The pharmaceutical composition of claim 1, wherein the sucrose is at a concentration of 80 mg/mL.
5. The pharmaceutical composition of claim 1, wherein the concentration of polysorbate 80 is 0.3 mg/mL.
6. The pharmaceutical composition of claim 1, wherein the pH of the pharmaceutical composition is 5.5-6.5.
7. The pharmaceutical composition of any one of claims 1-6, wherein the anti-IL-17A antibody or antigen-binding fragment thereof comprises a heavy chain variable region as set forth in SEQ ID No. 7 and a light chain variable region as set forth in SEQ ID No. 8.
8. The pharmaceutical composition of claim 7, wherein the anti-IL-17A antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID No. 9 and a light chain as set forth in SEQ ID No. 10.
9. A lyophilized formulation, characterized in that it is obtained by freeze-drying the pharmaceutical composition according to any one of claims 1-8, or that it can be reconstituted to form the pharmaceutical composition according to any one of claims 1-8.
10. Use of a pharmaceutical composition according to any one of claims 1-8 or a lyophilized formulation according to claim 9 in the manufacture of a medicament for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, axial spondylitis, psoriatic arthritis, hidradenitis suppurativa, palmoplantar pustulosis, inflammatory bowel disease, multiple sclerosis or multiple myeloma.
CN202410479487.XA 2024-04-19 2024-04-19 Pharmaceutical compositions comprising antibodies targeting IL-17A Pending CN118078988A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202410479487.XA CN118078988A (en) 2024-04-19 2024-04-19 Pharmaceutical compositions comprising antibodies targeting IL-17A

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202410479487.XA CN118078988A (en) 2024-04-19 2024-04-19 Pharmaceutical compositions comprising antibodies targeting IL-17A

Publications (1)

Publication Number Publication Date
CN118078988A true CN118078988A (en) 2024-05-28

Family

ID=91153371

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202410479487.XA Pending CN118078988A (en) 2024-04-19 2024-04-19 Pharmaceutical compositions comprising antibodies targeting IL-17A

Country Status (1)

Country Link
CN (1) CN118078988A (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107849128A (en) * 2015-07-16 2018-03-27 伊莱利利公司 Itch is treated
CN110585430A (en) * 2019-09-29 2019-12-20 华博生物医药技术（上海）有限公司 Pharmaceutical composition of humanized anti-human IL-17A monoclonal antibody
CN110898220A (en) * 2019-04-02 2020-03-24 Biocad股份公司 Aqueous pharmaceutical composition of anti-IL 17a antibody and application thereof
CN112915201A (en) * 2019-12-06 2021-06-08 珠海市丽珠单抗生物技术有限公司 Liquid formulations comprising anti-IL-17 antibodies
CN115768476A (en) * 2020-06-10 2023-03-07 上海君实生物医药科技股份有限公司 anti-IL-17A antibody pharmaceutical composition and application thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107849128A (en) * 2015-07-16 2018-03-27 伊莱利利公司 Itch is treated
CN110898220A (en) * 2019-04-02 2020-03-24 Biocad股份公司 Aqueous pharmaceutical composition of anti-IL 17a antibody and application thereof
CN110585430A (en) * 2019-09-29 2019-12-20 华博生物医药技术（上海）有限公司 Pharmaceutical composition of humanized anti-human IL-17A monoclonal antibody
WO2021058005A1 (en) * 2019-09-29 2021-04-01 华博生物医药技术（上海）有限公司 Pharmaceutical composition containing humanized anti-human il-17a monoclonal antibody
CN112915201A (en) * 2019-12-06 2021-06-08 珠海市丽珠单抗生物技术有限公司 Liquid formulations comprising anti-IL-17 antibodies
CN115768476A (en) * 2020-06-10 2023-03-07 上海君实生物医药科技股份有限公司 anti-IL-17A antibody pharmaceutical composition and application thereof

Similar Documents

Publication Publication Date Title
US20230047111A1 (en) Pharmaceutical formulations of tnf-alpha antibodies
EP2844286B1 (en) Lyophilised and aqueous anti-cd40 antibody formulations
JP5896471B2 (en) Antibody preparation
EP2648750B1 (en) Antibody formulation
JP2009521482A (en) Low viscosity protein formulations and uses thereof
TWI761869B (en) Formulation containing anti-cd47 / pd-l1 bispecific antibody and preparation and use thereof
JP7089121B2 (en) Protein solution preparation containing high concentration of anti-VEGF antibody
KR20210078514A (en) Formulations of anti-RSV antibodies and methods of use thereof
RU2745814C1 (en) Aqueous pharmaceutical composition of levilimab and the use thereof
CN118078988A (en) Pharmaceutical compositions comprising antibodies targeting IL-17A
KR20210096105A (en) Stabilization formulations containing anti-PCSK9 antibodies
WO2023098694A1 (en) Anti-sost antibody pharmaceutical composition and use thereof
EP4151233A1 (en) Preparation comprising anti-il-23p19 antibody, preparation method therefor and use thereof
CN117159703B (en) Pharmaceutical composition containing anti-LAG-3 antibody and application thereof
WO2023226617A1 (en) Stable antibody preparation
CN116172947A (en) Pharmaceutical composition containing bispecific antibody specifically binding VEGF and ANG2
CN114652825A (en) Stable antibody preparation, preparation method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination