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/IN2021/051095 (filing date 11/24/2021), which claims the benefit of the prior-filed Indian Provisional Patent Application No. IN202041051228 (filing date 11/25/2020).
Status of Application/Claims
The preliminary amendment, filed 05/23/2023, is acknowledged. Claim 7 is canceled. Claims 3, 6, and 9-10 are currently amended. Claims 11-13 are new. Claims 1-6 and 8-13 are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/23/2023 has been fully considered by the examiner.
Claim Objections
Claim 3 objected to because of the following informalities:
Claim 3 recites, “…one or more of the following excipients, i) sugar, ii) amino acid, iii) surfactant” which should be corrected to “…one or more of the following excipients: i) sugar, ii) amino acid, and/or iii) surfactant”.
Appropriate correction is required.
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 6 and 8 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.
Claims 6 and 8 recite, “A method…does not require an anti-oxidant.” It is unclear if the absence of an anti-oxidant is a requirement of the claim or if an anti-oxidant can be present. Thus, claims 6 and 8 are rejected because the scope of the claims is indefinite.
For further examination, the claims are interpreted to mean that the absence of an anti-oxidant is required, based on the following instant specification citations that suggest that methionine is an anti-oxidant and that aspects of the invention include methods wherein the formulation does not require any anti-oxidant:
“In another aspect… the formulation does not require any anti-oxidant or methionine” (p.2, lines 25-28).
“Examples of antioxidants herein include methionine, citrate, lipoic acid, uric acid, glutathione, tocopherol, carotene, lycopene, cysteine, phosphonate compounds…” (p.5, line 30 – p.6, line 2).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 11-13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 11-13 recite, “…wherein the anti-oxidant is methionine” and are dependent upon claims 2, 6, and 8, respectively, which recite:
Claim 2: “The formulation as claimed in claim 1, is devoid of anti-oxidant.”
and
Claims 6 and 8: “A method…does not require an anti-oxidant.”
As claims 2, 6, and 8 encompass any antioxidant and claims 11-13 specify methionine, claims 11-13 fail to further limit claims 2, 6, and 8, respectively.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 3-5, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over 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.
Joerg teaches pharmaceutical products and stable liquid compositions of IL-17 antibodies and processes of making these pharmaceutical products and compositions for treatment of IL-17-mediated disorders, including autoimmune disorders such as psoriasis, anklyosing spondylitis, psoriatic arthritis, and rheumatoid arthritis (title; abstract). Joerg teaches that various physical and chemical reactions can occur in solution that lead 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 teaches “ready-to-use” pharmaceutical products and liquid compositions of IL-17 antibodies and antigen binding fragments, including secukinumab (p.2, para.2). Joerg further teaches 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). Joerg teaches that the compositions have a range of IL-17 antibody concentrations ranging from 25 mg/mL up to high concentrations of 150 mg/mL (p.3, para.5; p.4, para.4, Fig.1). Joerg teaches buffers and pHs for the compositions. Buffers include histidine buffer, citrate buffer, and acetate buffer. Jeorge 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). 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 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 (p.25, para4 – p.26, para.1; Fig.13C). Joerg teaches that 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, amino acids, and surfactants (p.26, para.2 – p.27, paras.1-2; p.27, para 4; 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 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 does not teach a singular aqueous high concentration anti-IL-17 antibody formulation that specifically comprises a trehalose or mannitol sugar excipient (instant claims 3-4), an arginine amino acid (instant claims 3 and 5), and/or a surfactant excipient (instant claim 3); organic base histidine (instant claim 9); or, weak organic acid acetate or citrate (instant claim 10).
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 combine the teachings of Joerg by formulating a liquid pharmaceutical composition that is an aqueous composition comprising at least one IL-17 antibody and at least one additional excipient/buffer, additional excipients including stabilizers and surfactants, and additional active ingredients (taught by Joerg) by modifying the formulation to include 150 mg/mL anti-IL-17 antibody in buffer comprising histidine base and an acetate or citrate weak organic acid at a pH within the range of 5.5 to 6.5 (also taught by Joerg), to arrive at the instantly claimed invention, because the combination of prior art taught by Joerg according to known methods results in a predictable result. One of ordinary skill in the art would have a reasonable expectation of success because Joerg teaches that such pharmaceutical compositions can be formulated to be compatible with the intended route of administration for the treatment of autoimmune disorders. Further, Joerg teaches the benefits that histidine and citrate buffers provide advantages in aggregation and degradation. Further, it would have also been obvious to further combine the teachings of Joerg by modifying the formulation to include trehalose or mannitol sugar, arginine or methionine amino acid, and/or surfactants to arrive at the instantly claimed invention because Joerg also teaches the expected benefits that including such excipients serves to further stabilize the formulation (i.e., reducing degradation and aggregation); and, Joerg further teaches that methionine additionally has anti-oxidant properties (i.e., controlling oxidation).
Claims 1-6 and 8-13 are rejected under 35 U.S.C. 103 as being unpatentable over Joerg, as applied to claim 1 above, in further view of Di Padova, et al. US7807155B2 – IL-17 antagonistic antibodies. Effective filing date: 03/02/2007, PCT Publication date: 02/09/2006, Issue date: 10/05/2010, herein referred to as Di Padova; ; and further in view of Li, et al. Chemical instability of protein pharmaceuticals: Mechanisms of oxidation and strategies for stabilization. Biotechnology and Bioengineering (1995), 48, p.490-500, herein referred to as Li.
Joerg teaches aqueous high concentration 150 mg/mL IL-17 antibody pharmaceutical formulations comprising acetate or citrate weak organic acids and histidine organic base buffers; formulations with one or more excipients that are trehalose or mannitol sugar, arginine amino acid, and/or surfactant; methionine anti-oxidant for controlling oxidation; and, formulations of pH of about 5.5 to about 6.5 for stabilizing the formulation, reducing aggregation and degradation, and inhibiting acidic and basic (charge) variants, as described in detail for claim 1 above.
Joerg does not teach that the formulation is devoid of antioxidant/methionine (instant claims 2 and 11); that the method of inhibiting charge variants and aggregation comprises in a formulation that does not require an anti-oxidant/methionine (instant claims 6 and 12); or, that the method of controlling oxidation comprises a formulation that does not require an anti-oxidant/methionine (instant claims 8 and 13).
Di Padova also teaches IL-17 antibody formulations, including liquid and lyophilized formulations for treatment of disease, including prophylaxis and treatment of autoimmune diseases including arthritis, rheumatoid arthritis, aklyosing spondylitis, psoriatic arthritis, and psoriasis (as Joerg), among other conditions (title; abstract; p.13, col.18, para.6). The prior art of Di Padova teaches formulations wherein an antioxidant/methionine is not required.
Li teaches that oxidation is one of the major chemical degradation pathways for protein pharmaceuticals and that amino acid residues most susceptible to oxidation are methionine, cysteine, histidine, tryptophan, and tyrosine (abstract). Li teaches that protein oxidation may result in loss of biological activity; and strategies to stabilize proteins against oxidation including physical methods (solid vs. liquid formulations), intrinsic methods (site-directed mutagenesis and chemical modification), and use of chemical additives (abstract). Li teaches chemical additives can be anti-oxidants, chelating agents, or other additives. Li further teaches specific chelating agents EDTA, amino acids, phosphoric acid, and tartaric acid that provide the benefits of removing catalyzing metals such as iron and copper (p.497, col.2, para.3). Li also teaches specific “other additives” can be polyols and sugars, and that these components provide additional benefits of enhancing protein solubility, protein confirmation stabilization, and inhibit metal-catalyzed oxidation of proteins and peptides (p.497, col.2, para.4).
Regarding claims 2, 6, 8, and 11-13, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to combine the teachings of Joerg with the teachings of Di Padova and Li by modifying the IL-17 antibody formulation (taught by Joerg and Di Padova) to comprise a chemical additive such as a chelating agent, sugar, and/or amino acids in order to arrive at the instantly claimed invention, in order to receive the expected benefits (as taught by Joerg and Li) that including these additives would provide for protein oxidation protection, solubility, and stabilization (i.e., reduced degradation and aggregation). One of ordinary skill would have a reasonable expectation of success because Joerg and Di Padova teach IL-17 antibody formulations and Joerg teaches EDTA, sugars, and amino acids as stabilizers for IL-17 antibody formulations, as well as anti-oxidant methionine. Further, an IL-17 formulation with a non-methionine, non-antioxidant additive such as chelating agents, sugars, and/or amino acids instead of methionine antioxidant would be a simple substitution of one known element for another in order control oxidation in the pharmaceutical formulation.
Conclusion
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647