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 claims benefit to PCT/KR2022/003207 (filed on 03/07/2022) and KR10-2021-0030501 (filed 03/09/2021) and is acknowledged. The instant claims herein are examined using the effective filing date of 03/09/2021 for the basis of any prior art rejections.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted 09/07/2023, 11/04/2024, and 09/23/2025 were properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) were considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete. The sequence listing is in kilobytes, not bytes.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Interpretation
Claim 22-24 recite, inter alia, that the formulation is “for subcutaneous administration” (claim 22), and “for the prevention or treatment of an allergic disease” (claim 23) and “wherein the allergic disease is one selected from the group consisting of food allergy, atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, chronic idiopathic urticaria, chronic spontaneous urticaria, and allergic contact dermatitis” (claim 24). The examiner has interpreted these limitations as intended uses of the aqueous pharmaceutical formulation of claim 20. Please note that
the language after the word “for” does not impart any meaningful limitation to the claimed
invention. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed
invention, and the preamble merely states, for example, the purpose or intended use of the invention,
rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not
considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite
Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (see MPEP 2111.02). Please
note that as the claims are interpreted as intended uses of the composition of claim 1, any prior art pharmaceutical composition, would, absent evidence to the contrary, be suitable for the claimed intended uses.
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.
Claim 7 is 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 7 recites, inter alia, “the extracellular domain of the alpha subunit of the IgE Fc receptor consists of the amino acid sequence of SEQ ID NO: 1 or a fragment thereof”. The claim utilizes “consists of” language (i.e., closed language) for SEQ ID NO: 1, but also recites that the sequence can also include, essentially, any fragment of SEQ ID NO: 1 (e.g., a sequence that is 2 amino acids long). Thus, the claim is indefinite because it is unclear whether the claim is closed only to the amino acid of SEQ ID NO: 1 (i.e., 100% sequence identity) or if the claim is open to any and all fragments of SEQ ID NO: 1. For the purposes of compact patent prosecution, the examiner is interpreting the claim to encompass SEQ ID NO: 1 as well as any and all fragments of the sequence (i.e., open language).
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
Claim interpretation: The independent claim (and thus the dependent claims) requires “an aqueous pharmaceutical formulation comprising: a fusion protein dimer comprising an extracellular domain of an alpha subunit of an IgE Fc receptor (FceRIa ECD), wherein the pH of the formulation is from 6.0 to 7.0.” Claim 4 requires, inter alia, the formulation to include a modified Fc region linked to the IgE Fc receptor via a hinge. Claim 6 requires the hinge to be a hinge region derived from IgD or a variant thereof. Claim 7 requires the extracellular domain of the alpha subunit of the IgE Fc receptor consists of the amino acid sequence of SEQ ID NO: 1 or a fragment thereof.
The specification defines “modified Fc region” as “a region obtained by substituting some amino acids in the Fc region or by combining different types of Fc regions” (see pg. 7 of the specification). Thus, this limitation is interpreted by the examiner to encompass any Fc regions modified by any substitution or combination of different types of Fc regions.
The term “variant” has not been explicitly defined in the specification, however pg. 8 of the specification discloses that “the hinge of the IgD antibody may be a hinge variant obtained by modifying the hinge region. . . Here, the hinge variant may be obtained by modifying some [amino acids] in a hinge sequence of the IgD antibody in order to minimize the generation of truncated forms during a protein production process.” Thus, this limitation is interpreted by the examiner to encompass any immunoglobulin hinge variant, including those obtained by some nebulous amino acid modifications.
The term “fragment” has not been explicitly defined in the specification however, pg. 7 of the specification discloses “the extracellular domain of the alpha subunit of the IgE Fc receptor may be a fragment or variant of the extracellular domain of the alpha subunit of the IgE Fc receptor, as long as the fragment or variant is capable of binding to IgE. The variant may be prepared through a method of substituting, deleting, or adding one or more proteins in the wild-type FceRIa ECD (extracellular domain), as long as the method does not alter a function of the [alpha] chain of FceRI.” Thus, this limitation is interpreted by the examiner to encompass any fragment of the alpha subunit of the IgE Fc receptor, including functional fragments that retain the capability to bind to IgE.
The claims encompasses any modified Fc region, any variant of the claimed IgD hinge, and any partial fragment of SEQ ID NO: 1 having some nebulous mutations that would somehow function as a IgE Fc receptor. The question at issue is whether the skilled artisan would have understood Applicant to have been in possession of the massive genus of modified Fc regions, IgD hinge variants, and functional fragments of SEQ ID NO: 1 as encompassed by the instant claims.
Reduction to practice and disclosure of drawings or structural chemical formulas: Applicant discloses in the specification preparation of FceRIa fusion protein dimer using the amino acid sequence of SEQ ID NO: 1 and modified immunoglobulin Fc of SEQ ID NO: 2 linked via a hinges of SEQ ID NO: 19, SEQ ID NO: 3, and SEQ ID NO: 4 to create composition GI-301 before creation of an aqueous formulation (see Example 1, pg. 10; Example 2; pg. 14).
Sufficient, relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure: Applicant has not provided information as to the defining structural characteristics that would lead one of ordinary skill in the art to the identity of modified Fc regions, any variant of the claimed IgD hinge, and any partial fragment of SEQ ID NO: 1 having some nebulous mutations that would somehow function as a IgE Fc receptor in a pharmaceutical composition as claimed. Applicant’s claims encompass modified Fc regions, variants of the IgD hinge, and any partial fragment of SEQ ID NO: 1, all of which can include any number of amino acid sequence modifications/substitutions/deletions/etc., and can include both canonical or non-canonical amino acid mutations. However, Applicants have not disclosed which portion of the amino acids are necessary for the creation of the fragments and variants capable for use in the pharmaceutical composition. Even with knowledge in the art regarding amino acid modifications, one of ordinary skill would not know what structural features of the Fc region, IgD hinge, and fragments of SEQ ID NO: 1 are required for the outcome of creating a pharmaceutical that retains functional IgE binding activity without a recognized correlation between structure and function. This is not sufficient to meet the written description requirement. The specification does not provide adequate disclosure for sequences with that much variation for the claimed purpose.
Lack of support for massive genus of hDHFR mutants: The specification fails to teach and/or provide support for possession of the variants, fragments, etc. as there is no correlation or defining characteristic that would convey the identity of variants with the ability to perform the function as broadly claimed.
In support of the claimed genus, the specification demonstrates possession of the amino acid sequence of SEQ ID NO: 1 and modified immunoglobulin Fc of SEQ ID NO: 2 linked via a hinges of SEQ ID NO: 19, SEQ ID NO: 3, and SEQ ID NO: 4 to create composition GI-301 before creation of an aqueous formulation (see Example 1, pg. 10; Example 2; pg. 14). Applicant has only demonstrated possession of: the modified immunoglobulin Fc region of SEQ ID NO: 2 (i.e., an amino acid with 100% sequence identity to SEQ ID NO: 2), the extracellular domain of the alpha subunit of SEQ ID NO: 1 (i.e., an amino acid with 100% sequence identity to SEQ ID NO: 1), and only the hinges of SEQ ID NO: 19, SEQ ID NO: 3, and SEQ ID NO: 4. for use in a pharmaceutical composition.
There is no support in the specification for the use of any modified Fc regions, any variant of the claimed IgD hinge, and any partial functional fragments of SEQ ID NO: 1. Thus, the data generated for the creation and use of the specific modified immunoglobulin Fc region, extracellular alpha subunit of IgE Fc receptor, and 3 IgD hinge amino acid sequences disclosed in the specification cannot reasonably be extrapolated to and applied to support possession of the entire claimed genus of modified Fc regions, variants of the claimed IgD hinge, and functional fragments of SEQ ID NO: 1 as claimed, because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the claimed genus of subject(s) in need thereof, i.e., additional complete or partial structures, other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or some combination thereof demonstrating possession of the claimed genus. Therefore, the claims are rejected under 35 U.S.C. 112(a) for lack of written description.
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.
Claims 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over Sung et al (WO 2019135668 A1; published 07/11/2019; hereinafter “Sung”) in view of Sloey et al (US 20170333559 A1; published 11/23/2017; hereinafter Sloey).
Sung teaches a pharmaceutical composition for treating or preventing an allergic disease comprising a polypeptide dimer comprising two monomers comprising the extracellular domain of the alpha subunit of the IgE Fc receptor (FceRIa-ECD) (as in claim 1) (see abstract, claim 1 and 8) that can be formulated for parenteral administration (i.e., an aqueous formulation; see pg. 5, paragraph 9).
Sung does not explicitly teach that the pH of the formulation is from 6.0-7.0.
However, Sloey (in a similar field of creation of liquid/aqueous pharmaceutical compositions) teaches reducing the viscosity of a liquid pharmaceutical formulation (see title, abstract, and claim 1). Sloey teaches that reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages/concentrations is done via inclusion of viscosity reducing excipients, buffers, stabilizers, surfactants, etc. (see paragraph 0003, 0032) and acceptable pHs of the pharmaceutical are pHs between about 4.0 to about 8.0 (see paragraph 0033; claim 16). Please note that the pH range as instantly claimed lies inside the range disclosed by the prior art. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see MPEP 2144.05).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the pharmaceutical composition of Sung and use the pH disclosed by Sloey to arrive at the claimed invention. As Sloey teaches reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages using acceptable pHs of the pharmaceutical between about 4.0 to about 8.0, one of ordinary skill would have been motivated to make the modification with a reasonable expectation of successfully creating a stable liquid pharmaceutical composition because Sloey teaches advantageous and known pH ranges for use in parenterally administered pharmaceuticals with reduced viscosity.
Regarding claim 2, Sung teaches the formulation can be for subcutaneous injection (see pg. 5).
Regarding claim 3, Sung teaches the fusion protein is two monomers comprising the extracellular domain of the alpha subunit of the IgE Fc receptor (FceRIa-ECD).
Regarding claim 4, Sung teaches that the monomer has a modified Fc region and the Fc region and FCeRIa are joined via a hinge (see claim 1; pg. 1).
Regarding claim 5, Sung teaches that the modfied Fc region is SEQ ID NO: 2 (see claim 3; pg. 3, paragraph 4) which has 100% sequence identity to instantly claimed SEQ ID NO: 2 (see alignment below):
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1085
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Regarding claim 6, Sung teaches that the hinge is an IgD antibody hinge (see claim 4; pg. 2, paragraph 7).
Regarding claim 7, Sung teaches the alpha subunit is SEQ ID NO: 1 (see claim 2) which has 100% sequence identity to instant SEQ ID NO 1 (see alignment below):
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833
821
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Regarding claim 8, Sloey teaches use of high concentrations of therapeutic proteins in pharmaceutical compositions, including at a concentration of at least 70 mg/mL to about 300 mg/mL (see paragraph 0021). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Please also note that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Regarding claim 9, Sung teaches that the pharmaceutical can include pharmaceutically acceptable adjuvants such as buffers (see pg. 4) and Sloey teaches that reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages/concentrations is done via inclusion of viscosity reducing excipients, buffers, stabilizers, surfactants, etc. (see paragraph 0003, 0032).
Regarding claims 10, 12, 14-15, and 17-18, Sloey teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., arginine, proline, histidine, lysine, glycine, methionine, etc.) or surfactants (e.g., polysorbate, including polysorbate 20, or polysorbate 80, or poloxamer, including poloxamer 188 (see paragraph 0035).
Regarding claim 11, , Sloey teaches that concentrations of buffers like histidine can be from about 1 mM to about 200 mM (see paragraph 0033).
Regarding claim 13, Sloey teaches the use of proline at 200 mM (see paragraph 0052, Table 1).
Regarding claim 16, neither Sung nor Sloey explicitly teach the use of methionine at the claimed concentrations. However, Sloey teaches that amino acids like methionine can be used in the formulation in an amount effective to further improve stability, reduce aggregation, and/or make the formulation isotonic, without significantly increasing viscosity (see paragraph 0041). Thus, one of ordinary skill would have been motivated, before Applicant’s filing date, to utilize methionine in a pharmaceutical composition in effective amounts to advantageously improve stability, reduce aggregation, and/or make the formulation isotonic, without significantly increasing viscosity. Please note that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Regarding claim 19, Sloey teaches concentrations of surfactant (e.g., poloxamer) may range from about 0.001% to about 1.0%, or from about 0.003% to about 0.5% (see paragraph 0035).
Regarding claim 20, as discussed above, the combination of Sung and Sloey renders prima facie obvious the aqueous pharmaceutical of claim 20.
Regarding claim 21, Sung teaches the pharmaceutical can be a parenteral dosage form, it may be formulated in the form of an injection, and Sloey teaches the formulation can be in a container including vials, tubes, bottles, single or multi-chambered pre-filled syringes, or cartridges, etc. (see paragraph 0046).
Regarding claim 22, Sung teaches the formulation can be for subcutaneous injection (see pg. 5).
Regarding claim 23, Sung teaches treating or preventing an allergic disease using the composition (see claim 12).
Regarding claim 24, Sung teaches the allergic diseases are food allergies, atopic dermatitis, asthma, allergic rhinitis, allergic conjunctivitis, allergic dermatitis, chronic idiopathic urticarial, and allergic contact dermatitis (see claim 13).
Accordingly, the claimed invention was prima facie obvious at the time of filing, especially in the absence of evidence to the contrary.
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.
First rejection
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 8-9, and 11-12 of U.S. Patent No. 12,410,233 B2 in view of Sloey. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below.
Regarding instant claim 1, patent claim 1, 2, 8 and 9 teaches a pharmaceutical composition having a polypeptide dimer having extracellular domain of aplpha subunit of an IgE Fc receptor.
None of the patent claims teach that the composition has a pH of 6-7.
However, Sloey teaches reducing the viscosity of a liquid pharmaceutical formulation (see title, abstract, and claim 1). Sloey teaches that reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages/concentrations is done via inclusion of viscosity reducing excipients, buffers, stabilizers, surfactants, etc. (see paragraph 0003, 0032) and acceptable pHs of the pharmaceutical are pHs between about 4.0 to about 8.0 (see paragraph 0033; claim 16). Please note that the pH range as instantly claimed lies inside the range disclosed by the prior art. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see MPEP 2144.05).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the pharmaceutical composition of ‘233 and use the pH disclosed by Sloey to arrive at the claimed invention. As Sloey teaches reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages using acceptable pHs of the pharmaceutical between about 4.0 to about 8.0, one of ordinary skill would have been motivated to make the modification with a reasonable expectation of successfully creating a stable liquid pharmaceutical composition because Sloey teaches advantageous and known pH ranges for use in parenterally administered pharmaceuticals with reduced viscosity.
Regarding claim 2, Sloey teaches the formulation can be for subcutaneous injection (see paragraph 0022).
Regarding claim 3, patent claim 1 teaches the polypeptide is two monomers comprising the extracellular domain of the alpha subunit of the IgE Fc receptor (FceRIa-ECD).
Regarding claim 4, patent claim 1 teaches that the monomer has a modified Fc region and the Fc region and FCeRIa are joined via a hinge.
Regarding claim 5, patent claim 1 teaches that the modfied Fc region is SEQ ID NO: 2 which has 100% sequence identity to instantly claimed SEQ ID NO: 2.
Regarding claim 6, patent claim 1 teaches that the hinge comprises the amino acid sequence of SEQ ID NO: 3 (the same sequence as disclosed in SEQ ID NO: 3 of the instant specification), such that patent claim 1 teaches the hinge as an IgD hinge.
Regarding claim 7, patent claim 1 teaches the alpha subunit is SEQ ID NO: 1 which has 100% sequence identity to instant SEQ ID NO 1.
Regarding claim 8, Sloey teaches use of high concentrations of therapeutic proteins in pharmaceutical compositions, including at a concentration of at least 70 mg/mL to about 300 mg/mL (see paragraph 0021). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Please also note that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Regarding claim 9, Sloey teaches that reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages/concentrations is done via inclusion of viscosity reducing excipients, buffers, stabilizers, surfactants, etc. (see paragraph 0003, 0032).
Regarding claims 10, 12, 14-15, and 17-18, Sloey teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., arginine, proline, histidine, lysine, glycine, methionine, etc.) or surfactants (e.g., polysorbate, including polysorbate 20, or polysorbate 80, or poloxamer, including poloxamer 188 (see paragraph 0035).
Regarding claim 11, , Sloey teaches that concentrations of buffers like histidine can be from about 1 mM to about 200 mM (see paragraph 0033).
Regarding claim 13, Sloey teaches the use of proline at 200 mM (see paragraph 0052, Table 1).
Regarding claim 16, neither the patent claims nor Sloey explicitly teach the use of methionine at the claimed concentrations. However, Sloey teaches that amino acids like methionine can be used in the formulation in an amount effective to further improve stability, reduce aggregation, and/or make the formulation isotonic, without significantly increasing viscosity (see paragraph 0041). Thus, one of ordinary skill would have been motivated, before Applicant’s filing date, to utilize methionine in a pharmaceutical composition in effective amounts to advantageously improve stability, reduce aggregation, and/or make the formulation isotonic, without significantly increasing viscosity. Please note that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Regarding claim 19, Sloey teaches concentrations of surfactant (e.g., poloxamer) may range from about 0.001% to about 1.0%, or from about 0.003% to about 0.5% (see paragraph 0035).
Regarding claim 20, the combination of the patent claims and Sloey renders prima facie obvious the aqueous pharmaceutical of claim 20.
Regarding claim 21, Sloey teaches the formulation can be in a container including vials, tubes, bottles, single or multi-chambered pre-filled syringes, or cartridges, etc. (see paragraph 0046).
Regarding claim 22, Sloey teaches the formulation can be for subcutaneous injection (see paragraph 0022).
Regarding claim 23 and 24, conflicting claim 11 and 12 teaches treating allergic disease, specifically food allergies.
Thus, it is clear that the claims are obvious variants of each other.
Second rejection
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 8-10 of U.S. Patent No. 12,409,203 B2 in view of Sloey. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below.
Regarding instant claims 1, 3-4 and 7, patent claim 1 teaches a polypeptide dimer comprising: a first monomer comprising an extracellular domain of an alpha subunit of an IgE Fc receptor (FcεRIα-ECD), a second monomer comprising an extracellular domain of an alpha subunit of an IgE Fc receptor (FcεRIα-ECD), wherein the FceRIα-ECD of the first and second monomers comprises the amino acid sequence of SEQ ID NO: 1, wherein the first monomer and the second monomer each contain an Fc region, and wherein the Fc region and the FcεRIα-ECD, in the first and second monomers, are linked via a hinge. Patent claim 8 teaches a composition of the dimer protein, and patent claim 10 teaches that the composition is a pharmaceutical composition.
However, Sloey teaches reducing the viscosity of a liquid pharmaceutical formulation (see title, abstract, and claim 1). Sloey teaches that reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages/concentrations is done via inclusion of viscosity reducing excipients, buffers, stabilizers, surfactants, etc. (see paragraph 0003, 0032) and acceptable pHs of the pharmaceutical are pHs between about 4.0 to about 8.0 (see paragraph 0033; claim 16). Please note that the pH range as instantly claimed lies inside the range disclosed by the prior art. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see MPEP 2144.05).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the pharmaceutical composition of ‘203 and use the pH disclosed by Sloey to arrive at the claimed invention. As Sloey teaches reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages using acceptable pHs of the pharmaceutical between about 4.0 to about 8.0, one of ordinary skill would have been motivated to make the modification with a reasonable expectation of successfully creating a stable liquid pharmaceutical composition because Sloey teaches advantageous and known pH ranges for use in parenterally administered pharmaceuticals with reduced viscosity.
Regarding claim 2, patent claim 9 teaches that the composition is for subcutaneous injection.
Regarding claim 5, patent claim 2 teaches the Fc region of the first and second monomers comprises the amino acid sequence of SEQ ID NO: 2.
Regarding claim 6, patent claim 3 teaches the hinge of the first and second monomers is a hinge region derived from immunoglobulin IgD or a variant thereof.
Regarding claim 8, Sloey teaches use of high concentrations of therapeutic proteins in pharmaceutical compositions, including at a concentration of at least 70 mg/mL to about 300 mg/mL (see paragraph 0021). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Please also note that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Regarding claim 9, Sloey teaches that reduction of liquid viscosity of pharmaceuticals containing therapeutic proteins at high dosages/concentrations is done via inclusion of viscosity reducing excipients, buffers, stabilizers, surfactants, etc. (see paragraph 0003, 0032).
Regarding claims 10, 12, 14-15, and 17-18, Sloey teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., arginine, proline, histidine, lysine, glycine, methionine, etc.) or surfactants (e.g., polysorbate, including polysorbate 20, or polysorbate 80, or poloxamer, including poloxamer 188 (see paragraph 0035).
Regarding claim 11, Sloey teaches that concentrations of buffers like histidine can be from about 1 mM to about 200 mM (see paragraph 0033).
Regarding claim 13, Sloey teaches the use of proline at 200 mM (see paragraph 0052, Table 1).
Regarding claim 16, neither the patent claims nor Sloey explicitly teach the use of methionine at the claimed concentrations. However, Sloey teaches that amino acids like methionine can be used in the formulation in an amount effective to further improve stability, reduce aggregation, and/or make the formulation isotonic, without significantly increasing viscosity (see paragraph 0041). Thus, one of ordinary skill would have been motivated, before Applicant’s filing date, to utilize methionine in a pharmaceutical composition in effective amounts to advantageously improve stability, reduce aggregation, and/or make the formulation isotonic, without significantly increasing viscosity. Please note that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
Regarding claim 19, Sloey teaches concentrations of surfactant (e.g., poloxamer) may range from about 0.001% to about 1.0%, or from about 0.003% to about 0.5% (see paragraph 0035).
Regarding claim 20, the combination of the patent claims and Sloey renders prima facie obvious the aqueous pharmaceutical of claim 20.
Regarding claim 21, Sloey teaches the formulation can be in a container including vials, tubes, bottles, single or multi-chambered pre-filled syringes, or cartridges, etc. (see paragraph 0046).
Regarding claim 22, patent claim 9 teaches the formulation can be for subcutaneous injection.
Regarding claim 23 and 24, none of the conflicting claims teach that the formulation is for treating or preventing allergies. However, as the claims have been interpreted (see above) to encompass an intended use of the claimed pharmaceutical composition), the patented composition and the claimed composition are, absent evidence to the contrary, useful for the claimed purpose.
Thus, it is clear that the claims are obvious variants of each other.
Conclusion
NO CLAIMS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
iKnowledge "Solutions" by Sudaxshina Murdan; posted 08/02/2015; accessed on 10/09/2025 from https://clinicalgate.com/solutions/#S0065: teaches solution requirements for parenteral (i.e., injectable) forms of administration, where parenteral solutions should have a pH close to physiological pH to avoid pain, phlebitis, and tissue necrosis. Since a reasonably wide pH range can be tolerated, the pH of most licensed parenteral solutions is between 3 and 9 (see Table on pg. 7).
Thomas et al (2D Analysis of Protein Therapeutics and Amino Acid Excipients with Combined UV and Charged Aerosol Detection; 11/16/2016; accessed 10/09/25 from https://documents.thermofisher.com/TFS-Assets/CMD/posters/PN-71849-HPLC-Protein-Therapeutics-Amino-Acid-Excipients-UV-CAD-EAS2015-PN71849-EN.pdf): discusses protein therapeutic formulations, and inclusion of amino acid excipients to improve stability including proline, histidine, and methionine. These amino acids serve as buffers, bulking agents, stabilizers, and antioxidants to help adjust final pH, and suppress aggregation (see pg. 1, paragraph 3-4).
Wang et al. Solution Stability of Poloxamer 188 Under Stress Conditions. J Pharm Sci. 2019 Mar;108(3):1264-1271: discusses “Poloxamer 188 (P188) is a triblock copolymer of the form polyethylene oxide-polypropylene oxide-polyethylene oxide (PEOePPOePEO). The center PPO block is hydrophobic, and the side PEO blocks are hydrophilic, resulting in surface-active properties. P188 has been used in the pharmaceutical industry as an excipient in various formulations and drug delivery systems. Although the chemical stability of P188 in the solid state has been reported, there are very few reports detailing the solution state stability, the solution state stability of P188 conducted to evaluate the effects of P188 concentration, temperature, pH and buffer type, and trace metals on chemical stability” (see abstract, throughout).
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672