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 .
Election/Restrictions
Applicant’s election without traverse of species (a) acetate buffer, (b) sucrose as the tonicity modifier, (c) proline as the neutral amino acid, (d) a receptor protein as the heterologous polypeptide, (e) polysorbate as the non-ionic surfactant, and (f) phenol as the preservative in the reply filed on 7/30/2026 is acknowledged.
Status of Application, Amendments, And/Or Claims
Claims 1-8, 10-11, 14, 16-17, 19-25, 27-29, 31, 33,36-37, 39, 41 and 45 are pending.
Claims 17, 24-25, 28-29, 31 and 33 are withdrawn for being drawn to non-elected species.
Claims 1-8, 10-11, 14, 16, 19-23, 27, 36-37, 39, 41 and 45 are under examination to the extent they read on elected species.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 8/15/2023, 11/14/2023, 2/26/2024, 9/9/2025, 1/30/2026 and 5/5/2026 have been considered.
Specification
The disclosure is objected to because of the following informalities:
The use of the term “ELOCTATE” and “ALPROLIX”, which is a trade name or a mark used in commerce, has been noted in this application (page 13, lines 2-3). The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-8, 10-11, 14, 16, 19-23, 27, 36, 41 and 45 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 1-8, 10-11, 14, 16, 19-23, 27, 36, 41 and 45 are rejected as being indefinite because it is not clear if one more buffers are comprised in the claimed aqueous solution. For example, lines 4-6 of claim 1 recite, "optionally one or more buffers being substances having at least one ionisable group with a pKa in the range of 3.0 to 9.5 and which pKa is within 2 pH units of the pH of the composition". Meanwhile, claim 1, line 9, also recites "wherein the buffers are present in the composition at a total concentration of 0-10 mM" (emphasis added by Examiner).
Therefore, in view of these two conflicting phrases in claim 1, it is not clear if the buffer is optional in the solution or if it is required. Dependent claims 2-4, 6, and 7 recite buffer limitations (suggesting that the buffer is required) and dependent claim 5 recites that the composition is substantially free of buffers. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 2-8, 10-11, 14, 16, 19-23, 27, 36, 41 and 45 depend on a broad and indefinite claim.
Claim 23 contains the trademarks/trade names "ELOCTATE" and "ALPROLIX".
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 trademarks/trade names are used to identify/describe an antihemophilic factor-Fc fusion protein and a coagulation factor IX-Fc fusion protein, respectively, and accordingly the identification/description is indefinite.
Claim Rejections - 35 USC § 102
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 –
Claim(s) 1-8, 10-11, 14, 16, 19-23, 27, 36 and 45 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (US Pub. No. 2019/0276528).
The instantly claimed invention is broadly drawn to an aqueous solution comprising an engineered protein construct comprising an Fc domain, one or more buffer with a pH in the range of 4-8.5 (pKa in a range of 3-9.5), a neutral amino acid, wherein the buffers are present in about 0mM-10 mM with total ionic contribution <20 mM (claim 1-6), wherein the buffer comprises pKa within 1 unit of the pH of the composition (claim 7), wherein the buffer is citrate (claim 8), wherein the osmolarity is in a range of 200-600 msm/L (claim 10), wherein the uncharged tonicity modifier is sucrose (claim 11), wherein the neutral amino acid is proline (claim 14, 16), wherein the ionic strength of the composition is less than 10 mM and the pH is in a range of about 4-7.5 (claim 20-21), wherein heterologous polypeptide is a receptor protein (claim 22), wherein the Fc domain is an IgG Fc (claim 27), wherein the protein is about 1-400 mg/mL (claim 36), wherein a non-ionic surfactant is polysorbate20 or polysorbate 80 (claim 37, 39), and wherein the composition is a pharmaceutical composition (claim 45).
Regarding claim 1, 21-23,27 and 45, Liu et al. teach a stable pharmaceutical composition comprising a fusion protein aflibercept (see paragraph [0002]), wherein the fusion protein is a recombinant protein comprising Fc of an IgG fused to VEGFR (see [0004]).Regarding claim 36, they teach that the fusion protein can be present in concentration 1 mg/ml to about 200 mg /ml (see paragraph [0008]). Regarding claim 5, they teach that the composition can be buffer free (see paragraph [0009]). Regarding claims 2-4, 6, 20, they teach that the composition may comprise a buffer (see para [0020]) and the pH is about 5.5 to about 7.0 [0010, 0021]). Regarding claim 7, they teach that buffers maintain pH in a desired range, e.g., between pH 4 and pH 9 and buffers serve to stabilize a fusion protein by outside their buffer capacity using pKa values (see paragraph [0120]). Regarding claim 8, the teach that buffer may be selected from citrate buffer, acetate, histidine, phosphate, maleate or succinate (see [0023]), and because it is the same buffer (citrate) as recited in the claim the pKa would be attained in the same range, unless evidence to contrary. Regarding claim 6, they teach that buffer concentration is 5 mM to 10 mM (see [0024]). Regarding claims 14 and 16, they teach that the composition comprises a neutral amino acid glycine or arginine (see paragraph [0025]). Regarding claim 37 and 39, they teach that the non-ionic surfactant in the composition is a polysorbate 20 (see claim 16, paragraph [0271])). Therefore, the instantly claimed invention is implicitly or explicitly anticipated by the prior art of the record.
Claim(s) 1-7, 10-11, 14, 19-23, 27, 36, 41 and 45 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jezek et al. (IDS, US Pat. No. 2020/0069799).
The instantly claimed invention is broadly drawn to an aqueous solution comprising an engineered protein construct comprising an Fc domain, one or more buffer with a pH in the range of 4-8.5 (pKa in a range of 3-9.5), a neutral amino acid, wherein the buffers are present in about 0mM-10 mM with total ionic contribution <20 mM (claim 1-6), wherein the buffer comprises pKa within 1 unit of the pH of the composition (claim 7), wherein the buffer is citrate (claim 8), wherein the osmolarity is in a range of 200-600 mOsm/L (claim 10), wherein the uncharged tonicity modifier is sucrose (claim 11), wherein the neutral amino acid is proline (claim 14, 16), wherein the ionic strength of the composition is less than 10 mM and the pH is in a range of about 4-7.5 (claim 20-21), wherein heterologous polypeptide is a receptor protein (claim 22), wherein the Fc domain is an IgG Fc (claim 27), wherein the protein is about 1-400 mg/mL (claim 36), wherein a non-ionic surfactant is polysorbate20 or polysorbate 80 (claim 37, 39), wherein the composition of claim 1 comprises a preservative selected from the group of phenol, m-cresol, chlorocresol, benzyl alcohol being present at a concentration of 10-100 mM (claim 41), and wherein the composition is a pharmaceutical composition (claim 45).
Jezek et al. teach an aqueous solution comprising an antibody and a stabilizing mixture of a chelating agent which a multi-anion and a C3 polyol [0007]. They teach that an antibody can be a fragment fused to another active protein or a soluble receptor extracellular ligand binding domain fused an immunoglobulin Fc domain (see [0031]). Regarding claim 23, they teach that the fusion protein include etanercept, abatacept and belatacept, and additional proteins are for example aflibercept alefacept (see paragraph [0031]). Regarding claim 36, they teach that the fusion protein is present in about 1 mg/mL to 300 mg/mL (see [0037]). Regarding claims 1-7, they teach that the aqueous composition comprises a buffer selected from histidine, maleate, acetate, phosphate [0044]. They teach that the pH is about 5.0 to about 7.0 or 6.1 to about 8.1 [0045]. They teach that the composition comprises polysorbate 20 or polysorbate 80 as a surfactant [0047]. They teach that the composition may have osmolarity in the range of 200 mOsm/L to about 500 mOsm/L [0048]. They teach that the composition comprises an amino acid such as histidine [0050]. Regarding claim 41, they teach that the composition comprises a preservative selected from phenol, m-cresol, chlorocresol, benzyl alcohol and others (see paragraph [0052]). Regarding claim 45, they teach that the composition is pure to be used in a pharmaceutical use (see [0034, 0322, 0323]).
The applied reference has a common inventor (Jan Jezek) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 7-8,11,19-23, 27,36-37,41 and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 10-12, 14, 15,17, 23,25,27,29, 33,35 of copending Application No. 17/428341 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because an aqueous pharmaceutical composition comprising an engineered protein construct comprising an Fc domain, one or more buffer with a pH in the range of 4-8.5, a neutral amino acid, wherein the buffers are present in about 0mM-10 mM with total ionic contribution <20 mM, wherein the buffer comprises pKa within 1 unit of the pH of the composition, wherein the buffer is citrate, wherein the ionic strength of the composition is less than 10 mM and the pH is in a range of about 4-7.5 (claim 20-21), wherein heterologous polypeptide is a receptor protein (claim 22), wherein the Fc domain is an IgG Fc (claim 27), wherein the protein is about 1-400 mg/mL (claim 36), wherein a non-ionic surfactant is polysorbate20 or polysorbate 80 (claim 37, 39), wherein the composition of claim 1 comprises a preservative selected from the group of phenol, m-cresol, chlorocresol, benzyl alcohol being present at a concentration of 10-100 mM, and wherein the composition is a pharmaceutical composition are taught by claims 1-5, 7, 10-12, 14, 15,17, 23,25,27,29, 33,35 of copending Application No. 17/428341.
Claims 1-6, 11, 14, 19-23, 41, 27, 39, 41 and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 18, 22-23, 26, 34, 36, 38, 39 and 52 of copending Application No. 18/243767 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because an aqueous pharmaceutical composition comprising an engineered protein construct comprising an Fc domain, one or more buffer with a pH in the range of 4-8.5, wherein the composition is a pharmaceutical composition, wherein the composition comprises surfactant such as polysorbate 20 or polysorbate 80, wherein the composition comprises polyol as an uncharged tonicity modifier such as sucrose, wherein the aqueous composition comprises an amino acid, wherein the composition comprises etanercept are taught by claims 1, 12, 18, 22-23, 26, 34, 36, 38, 39 and 52 of copending Application No. 18/243767.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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