DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a 35 U.S.C. 371 national phase application, and claims
priority to, International Application No. PCT/CN2021/140083, filing date 12/21/2021.
This PCT application claims priority to Chinese Application No. PCTCN2020138273
filed 12/22/2020. Receipt is acknowledged of certified copies of papers required by 37
CFR 1.55.
Applicant is notified that to obtain the benefit of foreign priority under 35 U.S.C.
119(a)-(d) prior to declaration of an interference, a certified English translation of the
foreign application PCTCN2020138273 must be submitted in reply to this action. 37
CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no
benefit being accorded for the non-English application.
This correction is required to perfect priority (MPEP 216.01).
Status of Application/Claims
The preliminary amendment, filed 01/08/2024, is acknowledged. Claims 2, 4, 10, 14, 16, and 18 are canceled. Claims 5-9, 11-13, 15, 17, 19-25 are currently amended. Claim 26 is new. Claims 1, 3, 5-9, 11-13, 15, 17, and 19-26 are currently pending and are examined on the merits herein.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on 06/21/2023, 01/02/2025, and 03/27/2025 have been fully considered by the examiner.
Specification
The use of the terms Tween 20, Tween 80, Triton, Pluronic, Longer Pump (Longer Precision Pump Co., Ltd), Millipore, Bioscience, Thermo, Agilent, which are trade names or marks used in commerce, have been noted in this application. The terms should be in all caps wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 13 and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 contains the trademarks/trade names “Tween 80” and “Tween 20”; and claim 21 contains the trademark/trade name “Tween 80.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a surfactant and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 5, 9, 11-13, 15, 17, 19, and 24-25 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Joerg, et al. WO2016103153A1 – Pharmaceutical products and stable liquid compositions of IL-17 antibodies. Effective filing date: 12/22/2014, Publication date: 06/30/2016, herein referred to as Joerg; as evidenced by PubChem. Compound summary – Sorbitol. 1/1/2026. Internet – Wayback Machine. p.1-50 (herein referred to as PubChem1) and PubChem. Compound summary – Mannitol. 1/1/2026. Internet – Wayback Machine. p.1-48 (herein referred to as PubChem2).
Joerg teaches pharmaceutical products and stable compositions of IL-17 antibodies and processes of making these pharmaceutical products and compositions that can be administered to patients for treatment of IL-17-mediated disorders, including autoimmune disorders such as psoriasis, ankylosing spondylitis, psoriatic arthritis, diabetes, chromic plaque-type psoriasis, multiple sclerosis, and rheumatoid arthritis (title; abstract; p.1, para.3; p.2, para.1; p.39, para.4). Joerg specifically teaches a formulation comprising about 25 mg/mL – about 165 mg/mL anit-IL-17 antibody, about 10-30 mM histidine buffer, about 0.01% - about 0.03% polysorbate 80 surfactant (i.e., TWEEN 80), about 2.5 mM – about 20 mM methionine (which is within the range of 0.15% -- 1%), a stabilizer (i.e., trehalose sugar), having a pH of about 5.8 (p.43, para.4). Joerg also teaches formulations wherein the buffer is a citrate buffer of about 10 mM – about 30 mM (p.56, Example 5; Fig.16; p.61, claims 9-10). Joerg also teaches formulations wherein the histidine or citrate buffer is specifically 20 mM (p.61, claims 9-10). Further Joerg teaches that citrate buffer was found beneficial with regards to degradation products, and histidine buffer showed advantages in aggregation and degradation (p.25, para.3). Joerg also teaches formulations wherein the stabilizer is mannitol, which is a sugar alcohol (p.61, claim 17). Additionally, Joerg teaches compositions of anti-IL-17 antibody concentrations ranging from 20 mg/mL up to high concentrations of 175 mg/mL (p.60, claim 1). Joerg teaches “ready-to-use” pharmaceutical products and liquid compositions of IL-17 antibodies and antigen binding fragments, including secukinumab (p.2, para.2). Joerg also teaches amino acid SEQ ID NOs : 14 and 15, which encode the light and heavy chains of the secukinumab IL-17 antibody, respectively (see alignments below; [AltContent: textbox (Instant SEQ ID NO: 1 vs. Joerg SEQ ID NO: 14
[img-media_image1.png])]p.18, para.3):
[AltContent: textbox (Instant SEQ ID NO: 2 vs. Joerg SEQ ID NO: 15
[img-media_image2.png])]
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 5-8, 21-22 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Joerg; as evidenced by PubChem. Compound summary – Sorbitol. 1/1/2026. Internet – Wayback Machine. p.1-50 (herein referred to as PubChem1) and PubChem. Compound summary – Mannitol. 1/1/2026. Internet – Wayback Machine. p.1-48 (herein referred to as PubChem2).
Joerg teaches anti-IL-17 antibody formulations, including concentrations and types of buffers, stabilizers, and surfactants, as well as pH values for pharmaceutical formulations for the treatment of autoimmune disease as described in detail above for claims 1, 3, 5-6, 9, 11-13, 15, 17, 19, and 24-25. Joerg also teaches specific pharmaceutical formulations comprising an anti-IL-17 antibody of 150 mg/mL secukinumab (i.e., encoded by SEQ ID NOs 14 and 15; instant SEQ ID NOs 1 and 2), a buffer that is a histidine or citrate buffer at 20mM, a stabilizer that is a sugar alcohol mannitol or methionine, and a surfactant that is polysorbate 80, wherein the stabilizer is methionine and the formulation has a pH value of 5.8, as described in detail for claims 1, 3, 5-6, 9, 11-13, 15, 17, 19, and 24-25 above.
Joerg does not teach formulations that specifically comprise methionine at a concentration of about 0.4% or about 1% (instant claim 6); a sugar alcohol stabilizer that is at a concentration of about 3%-5% (instant claims 7 and 21) or about 3% or about 4% (instant claims 8 and 21); or, that the sugar alcohol is sorbitol (instant claims 22 and 26).
Joerg further teaches additional buffers and pHs for the compositions. Buffers include histidine buffer, citrate buffer, succinate buffer, phosphate buffer, acetate buffer, and combinations thereof (p.25, para.3). Jeorg teaches the effect of buffer species on stability, including acetate and citrate buffers (weak organic acids) and histidine buffers (organic base) (p.33, para.3; p.56, para.3). Joerg teaches 100mM citric acid/sodium phosphate buffer concentrations and histidine buffer concentrations ranging between 5mM to 50mM (p.25, para.3; p.34, para.3). Joerg also specifically claims histidine, citrate, acetate, and succinate buffers in the pharmaceutical product that are at buffer concentrations of about 10mM to about 30mM as well as histidine buffer of 20mM (p.61, claims 9-11p.34, para.3). Joerg teaches that the pH of the liquid composition may be in the range of about 5.5, about, 5.6, about 5.7, about 5.8, about 5.9, about 6, about 6.2, about 6.4, about 6.6 wherein lower pH values correspond to reductions in acidic variants and also shows stability of the IL-27 antibody buffer at 5.4 (p.25, para.4 – p.26, para.1; Fig.13C). Joerg teaches stabilizers and excipients that assist in preventing oxidation and aggregation of proteins in the pharmaceutical compositions, particularly liquid pharmaceutical compositions, which have a shorter shelf life due to tendency of proteins to oxidize and/or aggregative while in aqueous solutions (p.27, para.3). Joerg teaches ionic and non-ionic stabilizers including sugars (which can be a sugar alcohol or an amino sugar), amino acids (including methionine), and surfactants (p.26, para.2 – p.27, paras.1-2; p.27, para 4; p.28, paras.1-2; p.29, para.2). Joerg teaches that the sugar can be trehalose or mannitol which were regarded as beneficial stabilizers (p.27, para.4; p.35, para.3). Joerg teaches sugar alcohol (a “group 1 stabilizer”) concentrations for sorbitol and mannitol from about 175mM to about 350mM, which is from about 3.18%-6.37%, as evidenced by PubChem1 (i.e., sorbitol MW=182.71 g/mol) and PubChem2 (i.e., mannitol MW=182.17 g/mol) (i.e., includes from about 3%-5% as instantly claimed). Joerg teaches that the amino acid can be arginine or methionine (p.27, para.4; p.29, para.2). Joerg also teaches that methionine is advantageous in providing anti-oxidant properties (p.29, para.1). Joerg teaches methionine concentrations for compositions at 0.15%, 1%, and 2% (i.e., 10mM, 67mM, and 134mM, respectively; p.52, para.4; Fig.11; Example 3). Additionally, Joerg teaches that polysorbate 80 (i.e., Tween 80) and polysorbate 20 (i.e., Tween 20) can be used as the surfactant for the compositions (p.27, para.1); and, teaches polysorbate 80 concentrations of about 0.01-0.1% and polysorbate 20 concentrations of about 0.02% (p.27, para.1).
Joerg further teaches that various physical and chemical reactions can occur in solution that leads to an increase in degradation and/or loss of bioactivity including covalent and noncovalent aggregation, deamidation, oxidation, clipping, isomerization, and denaturation; and, that an acceptable liquid antibody composition must enhance stability and minimize protein degradation, especially protein aggregation, in order to avoid serious immunogenic reactions (p.2, para.1). Joerg also teaches assessment of acidic and basic variants (i.e., charge variants) in the compositions (p.10, para.3; Fig.13C).Joerg further teaches that formulations of “liquid pharmaceutical compositions” refers to aqueous compositions that contain at least one IL-17 antibody or antigen binding fragment and at least one additional excipient/buffer, and may include additional excipients including stabilizers and surfactants, and additional active ingredients; and, teaches that the compositions are formulated with excipients that are compatible with the intended route of administration (p.10, para.6; p.23, paras.4-5).
Regarding instant claim 6 as it relates to methionine concentration: The combination of Joerg’s teachings does not explicitly teach a methionine range of about 0.4% -- 1%. However, the methionine ranges taught by Joerg includes 0.15%, 1%, and 2%. Thus, the overall dosage range of 0.15% -- 2% taught by Joerg encompasses the instantly claimed dosage range of 0.4% -- 1%. Thus, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to further combine the teachings of Joerg by modifying the methionine concentration to be between about 0.4% -- 1%, to arrive at the claimed invention, because the combination of prior art elements according to the known methods of Joerg results in a predictable result and because one would use routine optimization to arrive at the methionine range of instant claim 6.
Regarding instant claims 7-8, 21-22, and 26 as they relate to a sugar alcohol stabilizer: It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Joerg by modifying the antibody formulation comprising a trehalose sugar stabilizer (taught by Joerg) to include a sugar alcohol stabilizer that is sorbitol or mannitol a concentration of 175 mM – 350 mM (i.e., 3.18% -- 6.37%; also taught by Joerg), to arrive at the instantly claimed invention, because the combination of prior art elements according to known methods results in a predictable result of providing protection against aggregation and degradation. As Joerg teaches that trehalose, mannitol, and sorbitol are all “group 1” stabilizers, this would be a simple substitution of one group 1 stabilizer for another.
Claims 20 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Joerg as applied to claim 1 above, and further in view of herein referred to as FDA. COSENTYX® -- Full prescribing information. June 2020. Reference ID: 4626087. p.1-36, herein referred to as FDA.
The combination of teachings by Joerg teaches an anti-IL-17 antibody, buffers, stabilizers, surfactants, and pH values for pharmaceutical formulations for the treatment of autoimmune disease, including specific pharmaceutical formulations comprising an anti-IL-17 antibody of 150 mg/mL secukinumab (i.e., encoded by SEQ ID NOs 14 and 15; instant SEQ ID NOs 1 and 2), a buffer that is a histidine buffer at 20mM, a stabilizer that is methionine or a sugar alchol, and a surfactant that is polysorbate 80 wherein the the formulation has a pH value of 5.8, as described in detail for claims 1, 3, 5-9, 11-13, 15, 17, 19, 21-22, and 24-26 above.
Joerg does not teach formulations wherein the anti-IL-17 antibody is expressed by a CHO cell (instant claim 20); or wherein the method of preparation comprises adding water for dissolving, mixing the substances and adjusting the volume to a specified volume (instant claim 23).
FDA teaches prescribing information for COSENTYX® (i.e., secukinumab, anti-IL-17 antibody) including indications and usage, dosage and administration, dosage forms and strengths, contraindications, warnings and precautions, adverse reactions, drug interactions, clinical pharmacology, toxicology, and storage and handling (p.1). FDA teaches dosages of 150 mg/mL antibody for injection via a single-use pen, prefilled syringe, or reconstitution of lyophilized powder for injection (p.1, col.2) for treatment of patients with autoimmune diseases including plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis (p.1, col.1). FDA teaches that secukinumab is a recombinant human monoclonal IgG1/κ antibody that binds specifically to IL-17A and is expressed in Chinese Hamster Ovary (CHO) cells (p.8, section 11-Description, para.1). FDA also teaches that the pharmaceutical is reconstituted/suspended in sterile water for injection (p.24, para.1; p.25, para.1) and provides detailed instructions for how to mix and dissolve the antibody at room temperature for a 1 mL solution (p.3, section 2.8; p.25). Further, FDA, teaches that COSENYTYX® Sensoready pens and prefilled syringes contain 150 mg secukinumab formulated in: L-histidine/histidine hydrochloride monohydrate, L-methionine, polysorbate 80, trehalose dihydrate, and sterile water for injection (p.9, para.1).
Regarding instant claim 20, it would have been prima facie obvious for one of ordinary skill in the art to further combine the teachings of Joerg with the teachings of FDA by using CHO cells to express the anti-IL-17 antibody (as taught by FDA) for the anti-IL-17 antibody formulation (taught by Joerg) to arrive at the instantly claimed invention, because the combination of prior art elements according to known methods results in a predictable result of CHO-mediated expression of the anti-IL-17 antibody. One of ordinary skill in the art would have a reasonable expectation of success because Joerg and FDA teach antibody formulations specifically for secukinumab which is a recombinant human monoclonal antibody.
Regarding instant claim 23, it would have been prima facie obvious for one of ordinary skill in the art to further combine the teachings of Joerg with the teachings of FDA by using a method of preparing an antibody formulation by dissolving an anti-IL-17 antibody (taught by Joerg and FDA) for a formulation that also contains buffer, stabilizer, and surfactant (as taught by Joerg) to arrive at the instantly claimed invention because FDA teaches methods for dissolving in sterile water, careful mixing methods for uniform mixing without shaking, and a volume of 1 mL for suspension and administration. One of ordinary skill in the art would have a reasonable expectation of success because Jeorg and FDA teach formulations of 150 mg/mL secukinumab anti-IL-17 antibody for the treatment of autoimmune disease, and FDA provides detailed instructions for preparation and administration of the formulation to patients with autoimmune disease.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jami M Gurley whose telephone number is (571)272-0117. The examiner can normally be reached Monday - Friday, 8am - 4pm.
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647