DETAILED ACTION
Status of claim rejections
The rejections of record under 35 USC 103 are maintained and modified in view of Applicant’s amendment to the claims in the response filed 07/17/2026.
The double patenting rejections of record are maintained and modified in view of Applicant’s amendment to the claims in the response filed 07/17/2026.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed 07/17/2026 has been entered.
Modified 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4, 7, and 21-24 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), and Zhou et al (Biotherapeutic formulation factors affecting metal leachables from stainless steel studied by design of experiments. AAPS PharmSciTech. 2012 Mar;13(1):284-94).
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 or using histidine and proline in the composition.
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) and concentrations of surfactant (e.g., poloxamer 188) may range from about 0.001% to about 1.0%, or from about 0.003% to about 0.5% (see paragraph 0035). 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).
Sloey also teaches that concentrations of buffers in the formulation like histidine can be from about 1 mM to about 200 mM (see paragraph 0033) and the use of proline at 200 mM (see paragraph 0052, Table 1). 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 (i.e., the therapeutic protein of Sung; 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).
Sloey further teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., proline, lysine, glycine, methionine, etc.) (see paragraph 0035) 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).
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.
Neither reference teaches using histidine-HCl.
However, Zhou teaches that biotherapeutic products are predominately formulated as liquids or freeze-dried products delivered by injection, and therefore fall into the category of parenteral formulations. In order to develop a stable formulation with an acceptable shelf life, excipients such as solvents/cosolvents, polymeric and surface-active compounds, chelating agents, antioxidants, preservatives, buffers, bulking agents, protectants, and tonicity adjusters, have been used in parenteral formulations. The majority of biologics products consist of a buffer, a tonicity modifier, a cryo- or lyoprotectant, and a surfactant. Zhou teaches methionine has been used as an antioxidant to protect labile methionine residues in proteins from oxidation and histidine buffer is commonly used to adjust the formulation pH for optimal stability and solubility (see pg. 284, col 1-2).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the formulation of Sung and Sloey and use histidine-HCl as taught by Zhou to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Zhou explicitly teaches buffers like histidine HCl are commonly used in biopharmaceutical formulations to make them stable with an acceptable shelf life and adjusting pH for optimal stability/solubility.
Regarding claim 2, Sung teaches the formulation can be for subcutaneous injection (see pg. 5).
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), the modified 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). Sung also teaches the hinge is an immunoglobulin IgD-derived hinge region having the sequence of Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa1 Xaa2 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 17) where Xaa1 is Lys or Gly, and Xaa2 is Glu, Gly or Ser, or the hinge sequence is Ala Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa3 Xaa4 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 18) where Xaa3 is Lys or Gly, and Xaa4 is Glu, Gly or Ser (see claims 6 and 7 of Sung).
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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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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.
Response to Arguments
Applicant's arguments filed 07/17/2026 have been fully considered but they are not persuasive.
On pg. 4-7 of the remarks, Applicant argues that neither Sung nor Sloey teaches the claimed invention as amended. Applicant argues Sloey fails to teach or suggest proline at a concentration of 240 mM to 260 mM because Sloey teaches 200 mM and no disclosure to increase the concentration to the claimed range. Applicant argues SLoey fails to teach histidine-HCl. Proline, and methionine at the claimed concentrations and that the specific combination of excipients exhibits unexpectedly superior effects (citing to Table 5 and 7 regarding formulation stability in the presence of histidine-HCl and proline, as well as table 9 and 13 regarding methionine for decreasing protein fragmentation.
In response, the examiner disagrees. Sung provides the teaching, suggestion, and motivation as to a pharmaceutical composition comprising a polypeptide dimer comprising two monomers comprising the extracellular domain of the alpha subunit FceRIa-ECD (as instantly claimed). Sloey provides a PHOSITA the teaching, suggestion, and motivation to use buffers/stabilizers such as histidine, methionine and proline and use a pH of 6-7 to advantageously stabilize and/or reduce viscosity of protein formulations in aqueous pharmaceutical compositions (see, e.g., paragraphs 0030, 0035, and 0039). The newly cited Zhou reference provides the teaching, suggestion, and motivation to use histidine-HCl to adjust the formulation pH for optimal stability and solubility. Thus, the combination of the teachings of the prior art references is in line with Applicant’s arguments regarding histidine-HCl). Furthermore, Applicant is reminded that the references teach concentrations that overlap or lie within Applicant’s claimed ranges. 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). As such, the rejection is maintained as set forth above.
On pg. 8-10 of the remarks, Applicant further argues that Sloey fails to teach or suggest the claimed range of poloxamer 188, arguing that the specification demonstrates that use of poloxamer 188 instead of Tween 80 allows for decreased turbidity in the claimed formulation, pointing to Table 10 of the specification, and that Sloey fails to disclose the FCeRI-alpha fusion protein because Sloey is drawn to IgG1 and G2 antibody formulations. Applicant argues that it is general knowledge in the art that formulation characteristics can vary depending on the sequence, type, and properties of the active ingredient like an antibody or protein such that one of ordinary skill would not have reasonably expected the excipient systems developed in Sloey would be directly applied to thet claimed fusion protein dimer, citing to Annexes 1-4 (given their fullest consideration.
In response, the examiner disagrees. As discussed above, Sung provides the teaching, suggestion, and motivation as to a pharmaceutical composition comprising a polypeptide dimer comprising two monomers comprising the extracellular domain of the alpha subunit FceRIa-ECD (as instantly claimed). Sloey, while using IgG1 and 2 antibodies, provides a PHOSITA the teaching, suggestion, and motivation to use buffers/stabilizers such as histidine and proline and use a pH of 6-7 to advantageously stabilize and/or reduce viscosity of protein formulations in aqueous pharmaceutical compositions (see, e.g., paragraphs 0030, 0035, and 0039). As such, the rejection is maintained as set forth above.
Modified 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 1-2, 7, 21-24 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 and Zhou. 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, and 8 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 or proline or histidine-HCl or methionine.
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). Sloey teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., histidine, proline, methionine, etc.) at 1 mM to about 200 mM, surfactants including poloxamer 188 may range from about 0.001% to about 1.0%, or from about 0.003% to about 0.5% (see paragraph 0035) and Sloey teaches the use of proline at 200 mM (see paragraph 0052, Table 1).
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). Sloey also teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., arginine, proline, histidine, lysine, glycine, etc.).
Sloey also 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).
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.
Further, Zhou teaches that biotherapeutic products are predominately formulated as liquids or freeze-dried products delivered by injection, and therefore fall into the category of parenteral formulations. In order to develop a stable formulation with an acceptable shelf life, excipients such as solvents/cosolvents, polymeric and surface-active compounds, chelating agents, antioxidants, preservatives, buffers, bulking agents, protectants, and tonicity adjusters, have been used in parenteral formulations. The majority of biologics products consist of a buffer, a tonicity modifier, a cryo- or lyoprotectant, and a surfactant. Zhou teaches methionine has been used as an antioxidant to protect labile methionine residues in proteins from oxidation and histidine buffer is commonly used to adjust the formulation pH for optimal stability and solubility (see pg. 284, col 1-2).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the formulation of ‘233 and use histidine-HCl as taught by Zhou to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Zhou explicitly teaches buffers like histidine HCl are commonly used in biopharmaceutical formulations to make them stable with an acceptable shelf life and adjusting pH for optimal stability/solubility.
Regarding claim 2, Sloey teaches the formulation can be for subcutaneous injection (see paragraph 0022).
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 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
Claim 4 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 and Sung. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below.
As discussed above, claim 1 is an obvious variant of the claimed invention.
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, the modfied Fc region is SEQ ID NO: 2 which has 100% sequence identity to instantly claimed SEQ ID NO: 2.
None of claims teach that the hinge is SEQ ID NO: 17 or 18.
However, 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) see abstract, claim 1 and 8) that can be formulated for parenteral administration (i.e., an aqueous formulation; see pg. 5, paragraph 9). 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), the modified 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). Sung also teaches the hinge is an immunoglobulin IgD-derived hinge region having the sequence of Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa1 Xaa2 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 17) where Xaa1 is Lys or Gly, and Xaa2 is Glu, Gly or Ser, or the hinge sequence is Ala Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa3 Xaa4 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 18) where Xaa3 is Lys or Gly, and Xaa4 is Glu, Gly or Ser (see claims 6 and 7 of Sung). Sung teaches these hinge sequences advantageously minimize the occurrence of truncations during the production of proteins.
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Therefore, it would have been prima facie obvious to modify the patent claims with the hinge of Sung to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Sung teaches the hinge minimizes the occurrence of truncations during the production of proteins.
As such, it is clear that the inventions are obvious variant of each other.
Third rejection
Claims 1-2, 7, 21-24 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 and Zhou. 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.
None of the patent claims teach that the composition has a pH of 6-7 or proline or histidine-HCl or methionine.
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). Sloey teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., histidine, proline, methionine, etc.) at 1 mM to about 200 mM, surfactants including poloxamer 188 may range from about 0.001% to about 1.0%, or from about 0.003% to about 0.5% (see paragraph 0035) and Sloey teaches the use of proline at 200 mM (see paragraph 0052, Table 1).
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). Sloey also teaches excipients or stabilizers may also be included, for example amino acids or amino acid derivatives (e.g., arginine, proline, histidine, lysine, glycine, etc.).
Sloey also 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).
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.
Further, Zhou teaches that biotherapeutic products are predominately formulated as liquids or freeze-dried products delivered by injection, and therefore fall into the category of parenteral formulations. In order to develop a stable formulation with an acceptable shelf life, excipients such as solvents/cosolvents, polymeric and surface-active compounds, chelating agents, antioxidants, preservatives, buffers, bulking agents, protectants, and tonicity adjusters, have been used in parenteral formulations. The majority of biologics products consist of a buffer, a tonicity modifier, a cryo- or lyoprotectant, and a surfactant. Zhou teaches methionine has been used as an antioxidant to protect labile methionine residues in proteins from oxidation and histidine buffer is commonly used to adjust the formulation pH for optimal stability and solubility (see pg. 284, col 1-2).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the formulation of ‘233 and use histidine-HCl as taught by Zhou to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Zhou explicitly teaches buffers like histidine HCl are commonly used in biopharmaceutical formulations to make them stable with an acceptable shelf life and adjusting pH for optimal stability/solubility.
Regarding claim 2, patent claim 9 teaches that the composition is for subcutaneous injection.
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.
Fourth rejection
Claim 4 is 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 and Sung. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below.
As discussed above, claim 1 is an obvious variant of the claimed invention.
None of claims teach that the hinge is SEQ ID NO: 17 or 18.
However, 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) see abstract, claim 1 and 8) that can be formulated for parenteral administration (i.e., an aqueous formulation; see pg. 5, paragraph 9). 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), the modified 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). Sung also teaches the hinge is an immunoglobulin IgD-derived hinge region having the sequence of Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa1 Xaa2 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 17) where Xaa1 is Lys or Gly, and Xaa2 is Glu, Gly or Ser, or the hinge sequence is Ala Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Xaa3 Xaa4 Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro (SEQ ID NO: 18) where Xaa3 is Lys or Gly, and Xaa4 is Glu, Gly or Ser (see claims 6 and 7 of Sung). Sung teaches these hinge sequences advantageously minimize the occurrence of truncations during the production of proteins.
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Therefore, it would have been prima facie obvious to modify the patent claims with the hinge of Sung to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because Sung teaches the hinge minimizes the occurrence of truncations during the production of proteins.
As such, it is clear that the inventions are obvious variant of each other.
Response to Arguments
Applicant's arguments filed 07/17/2026 have been fully considered but they are not persuasive.
On pg. 11-12 of the remarks, Applicant argues much of the same as it relates to the Sloey and Sung references regarding the double patenting rejections of record against the ‘203 and ‘233 patents (which will not be repeated here).
In response, the examiner disagrees for much of the same reasons as set forth above. As such, the rejections of record are maintained.
Conclusion
NO CLAIMS ALLOWED.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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