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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 on 09 February 2026 has been entered.
Claim Status
Claims 4, 6-9, 11-13, 16-23, 31, 33, 35, 37, 39-42, 44, 47, 49, 51-54, 56, 58, 63, and 69-74 are cancelled. Claims 1-3, 5, 10, 14-15, 24-30, 32, 34, 36, 38, 43, 45-46, 48, 50, 55, 57, 59-62, 64-68 and 75 as filed on 09 February 2026 are pending. Claims 4-15, 43, 45-46, 48, 50, 55, 57, 59-62, 64-68 withdrawn. Claims 1-3, 5, 10, 24-30, 32, 34, 36, 38, and 75 are under examination.
New Rejection
Claim Rejections - 35 USC § 112
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.
Claim 75 is 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.
MPEP § 2163 states that 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, or it may be satisfied by the 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 applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “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 one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Scope of the Claimed Genus
Claim 75 is to a pharmaceutical composition for the treatment of a fibroblast-mediated disease comprising a combined synergistic amount of a PTPRS de-clustering agent and a TNF inhibitor. The claim requires the PTPRS de-clustering agent is a PTPRS Ig1&Ig2 of at least 98% identity of instant SEQ ID NO: 17 and the TNF inhibitor is Etanercept wherein the Etanercept is at least 51% below a therapeutically effective amount of Etanercept when used individually.
Instant SEQ ID NO: 17 is 444 amino acids in length allowing for up to 8 amino acid changes within the sequence. SEQ ID NO: 17 is referred to by applicant as Construct 1 and comprises the mouse Ig 1 & 2, a linker, and an Fc ([0183] and [0249]).
Summary of Species Disclosed in the original specification
Applicant discloses a pharmaceutical composition with synergistic amounts for a PTPRS de-clustering agent of instant SEQ ID NO: 17, Construct 1, when used with Etanercept (Figure 11A-E and Figure 13 A-G and [0249]).
State of the Relevant Art
Fibroblast-like synoviocytes (FLS) are known therapeutics for mediating inflammation and joint destruction in rheumatoid arthritis. Receptor protein tyrosine phosphatases (RPTPs or PTPRs) have varying length extracellular domain (Bottini (WO 2014/018554 A1) (Of Record) (Hereafter “Bottini ‘554”) [0004]). The extracellular domain of RPTP proteins are separated into three immunoglobulin like domains: Ig1, Ig2, and Ig3 (Stanford & Bottini. Trends in Pharmacological Sciences. 38:524-540. (2017) (PTO-892) (Figure 3).
The extracellular domains Ig1 and Ig2 are known in the art for use in treatment of fibroblast mediated diseases either alone (Example 1 and [0124]). The art does not teach the variation of the Ig1 and Ig2 domains for use in its therapeutics (claims 1-9) and the Ig1 and Ig2 Bottini ‘554 has taught for use is not the same sequence as the one used in the fusion of instant SEQ ID NO: 17.
The art does not provide one of ordinary skill in the art with guidance on what are the core parts of the Ig1 and Ig2 region of instant SEQ ID NO: 17 for use in its therapeutics for a combined synergistic composition with etanercept.
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that 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.
The specification discloses a pharmaceutical composition with combined synergistic amounts of instant SEQ ID NO: 17 and etanercept where the therapeutic dose of Etanercept is at
The applicant has not shown the presence of combined synergistic amounts for PTPRS de-clustering agents that comprise sequences other than the disclosed Construct 1 of instant SEQ ID NO: 17.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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 applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity.
The applicant has not provided a core structure that provides the de-clustering activity required by claim 75 by instant SEQ ID NO: 17 other than instant SEQ ID NO: 17 in its entirety/ The applicant has now shown the synergistic activity when the amino acid sequence is varied.
Conclusion:
One of skill in the art would not know what amino acid changes to instant SEQ ID NO: 17 would remove the synergistic effects as a PTPRS de-clustering agent as no structure/function correlation is found in the specification or the art. The applicant has only shown a single species of a pharmaceutical composition comprising instant SEQ ID NO: 17 with Etanercept and has not shown that variation of instant SEQ ID NO: 17 would have this activity. The specification and the art do not provide guidance on the other species or structure of instant SEQ ID NO: 17 that would have the combined synergistic effect with Etanercept.
Applicant was not in possession of the invention as claimed.
Rejections Maintained – Updated as Necessitated by Applicant Amendment of Claims
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 5, 10, 24-26, 29-30, 32, 34, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO 2019042170 A1) (Of Record), Bottini (WO 2014/018554 A1) (Of Record) (Hereafter “Bottini ‘554”), and Hoffman (CA 2847142 C) (Of Record).
Regarding claims 1 and 4-5, Zhang teaches a combination of drugs for treating disease related to a tumor necrosis factor including rheumatoid arthritis. Zhang teaches the combination of an anti-inflammatory active drug with a TNFα inhibitor (Abstract). Zhang teaches the use of the applicant’s elected species of etanercept (page 2 in second to last line and Example 1). Zhang teaches the use of fibroblast-like synoviocites (FLS) in culture with the combination therapy comprising etanercept (Example 1). Zhang teaches the inhibition of FLS proliferation (page 5 in 3. Experimental Results).
Zhang does not teach a combination therapy comprising PTPRS de-clustering agent of Ig1 and Ig2 and does not teach a dose for etanercept that is at least 51% therapeutic dose that applicant has defined as 50 mg.
These deficiencies are filled by Hoffmann and Bottini ‘554.
Regarding claims 1-2 and 5, Hoffmann teaches the treatment of multiple diseases with TNFα inhibitors with multiple doses including induction/loading then maintenance and treatment phase (abstract). Hoffmann teaches the treatment of rheumatoid arthritis (page 4 in lines 5-21 in particular line 11). Hoffmann teaches the inhibitor is etanercept and teaches the induction dose is about 20 to 200 mg and the treatment dose is 20 to 120 mg (page 7 in lines 17-26) which would include doses of etanercept 51% or 52% below a therapeutically effective dose of the claims which is 50 mg stated in claim 5.
Regarding claims 1 and 23-26, Bottini ‘554 teaches the use of PTPRS extracellular domains called Ig1 and Ig2 interact with fibroblast-like synoviocytes (Example 1 in particular [0124]). Bottini ‘554 teaches a method of treatment for rheumatoid arthritis by administering a combination of Ig1 and Ig2 (Figures 11-16). Further, Bottini ‘554 teaches treatment with Ig1 and Ig2 resulted in improved clinical outcomes in a mouse model for rheumatoid arthritis and decreased tissue erosion and cartilage damage (Figure 15).
Regarding claims 10, 29-30, 32, 34, and 36, Bottini ‘554 teaches SEQ ID NO: 4 which matches amino acids 30-127 of instant SEQ ID NO: 4 and is taught as Ig1 (claims 4). Instant SEQ ID NO: 1 matches SEQ ID NO: 1 of Bottini ‘554 (claim 5). Amino acids 128 to 231 of instant SEQ IDNO: 4 matches SEQ ID NO: 4 of Bottini ‘554 (claim 6). Instant SEQ ID NO: 2 matches Bottini ‘554 SEQ ID NO: 2 (claim 7). Amino acids 232-321 of instant SEQ ID NO: 4 matches Bottini ‘554 SEQ ID NO: 4 (claim 8). Instant SEQ ID NO: 3 matches Bottini ‘554 SEQ ID NO: 3 (claim 9). Regarding the below a therapeutically effective level of the PTPRS de-clustering agent required by claim 10, Bottini ‘554 teaches a dose is the amount of active ingredient given to an individual that will vary based on condition being treated, size and tolerance of the subject, frequency of administration that can be modified by one of ordinary skill in the art as needed based on these factors ([0032]). Bottini ‘554 teaches the activity of Ig1 and Ig2 as a PTPRS de-clustering agents is as an anti-inflammatory (page 25 in lines 2-5 and Figure 2D). Bottini ‘554 further teaches that the agents of their invention can be used alone or in combination with any other treatment disclosed or known in the art ([0111]).
It would have been obvious at the time the application was filed to substitute the TNFα inhibitor and the inhibitor of FLS proliferation in the method of treating rheumatoid arthritis of Zhang with the etanercept at more than 51% below 50 mg of Hoffmann with the Ig1 and Ig2 as a PTPRS de-clustering agents of Bottini ‘554 to produce a pharmaceutical composition comprising etanercept and Ig1 and Ig2. One of skill in the art would have been motivated to optimize the pharmaceutical compositions for use in the method of Zhang with the known etanercept of Hoffmann and Ig1 and Ig2 of Bottini ‘554 as proven effective treatments for rheumatoid arthritis. Further, it would be obvious to substitute the generic TNFα inhibitors with the TNFα inhibitor of etanercept and the generic inhibitor of FLS proliferation with Ig1 and Ig2. There would have been a reasonable expectation of success as Zhang, Hoffmann, and Bottini ‘554 are all teaching pharmaceuticals in treatment of rheumatoid arthritis and Zhang teaches a combination therapy and Bottini ‘554 teaches the combination of their therapeutics with any other treatment known in the art.
Applicant Arguments
Applicant argues Zhang does not teach the combined drug composition of the claims and that the doses of Zhang are based on weight rations and molar rations related to additional parts of the composition of Zhang.
Applicant argues Bottini does not teach PTPRS Ig1&IG2 polypeptides and teaches the PTPRS de-clustering agent as a monotherapy. Applicant argues Bottini does not teach the combination with other therapies including not teaching TNF inhibitor.
Applicant argues Hoffman teaches a preferred neutralizing antibody of D2E7 and various doses for the TNF inhibitors. Applicant argues Hoffman does not teach or suggest use of TNF inhibitors with chlorogenic acid that Zhang teaches is used with its PTPRs de-clustering agents.
Applicant argues the following ways the art differs from the claims:
Zhang comprises a combination therapy of a chlorogenic acid and a TNFα inhibitor and dose is based on various weight and molar rations of additional agents.
Bottini does not suggest PTPRS de-clustering agent can be used at sub-therapeutic doses when combined with a TNF inhibitor and that it does not suggest combining with a TNF inhibitor.
Hoffman does not teach or suggest TNFα could be used at a suboptimal dose when combined with another therapeutic agent such as PTPRS de-clustering agents. Applicant argues the doses are for the preferred TNFα inhibitor D2E7 and not the other TNFα inhibitors.
Applicant argues the alterations of the art would render the invention of Zhang inoperable as the combination of chlorogenic acid with TNF inhibitor is reported as having synergistic effects and Zhang teaches the desirability of using chlorogenic acid for use. Applicant argues there is no motivation to combine Zhang with other
Response to Arguments
Applicant's arguments filed 02/09/2026 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Zhang is relied upon to teach a method of treating rheumatoid arthritis with the combination of a TNFα inhibitor and the inhibitor of FLS proliferation.
Bottini ‘554 is relied upon to teach an inhibitor of FLS that is effective in a method of treating autoimmune diseases. Bottini ‘554 further teaches that the agents of their invention can be used alone or in combination with any other treatment disclosed or known in the art ([0111]).
Hoffman is relied upon to teach doses for etanercept as Zhang provides no dosing for its TNF inhibitor.
The dosing of Hoffmann is explicitly taught as for any of their TNF inhibitors. When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012). Specifically, in In re Antor Media Corp., the court stated:
"Consistent with the statutory framework and our precedent, we therefore hold that, during patent prosecution, an examiner is entitled to reject claims as anticipated by a prior art publication or patent without conducting an inquiry into whether or not that prior art reference is enabling. As long as an examiner makes a proper prima facie case of anticipation by giving adequate notice under § 132, the burden shifts to the applicant to submit rebuttal evidence of nonenablement." In re Antor Media Corp., 689 F.3d at 1289, 103 USPQ2d at 1559.
Regarding the suboptimal or subtherapeutic dose applicant argues. Applicant has not provided a limiting definition for the claim language of at least 51% below a therapeutically effective level. The examiner has found multiple doses reported as therapeutic and reviewed the specification and applied the art and specification for determining the BRI of this claim language and finding doses below what was known in the art as a therapeutically effective level. The doses explicitly taught in the art to be administered are below what others in the art reported as therapeutically effective as explained in the art rejection.
Zhang teaches the method comprises the administration of its drug combinations simultaneously or separately (page 9 “Claims” in lines 1-4). The teachings of Zhang does not teach the separation of its TNF inhibitor and chlorogenic would render the method inoperable. Further, the instant claims are to a composition comprising PTPRS Ig1&IG2 polypeptides and etanercept, the composition of the claims could contain additional agents.
Claims 1, 27-28, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO 2019042170 A1) (Of Record), Bottini (WO 2014/018554 A1) (Of Record) (Hereafter “Bottini ‘554”), and Hoffman (CA 2847142 C) (Of Record) as applied to claims 1-3, 5, 10, 24-26, 29-30, 32, 34, and 36 above, and further in view of Huang. Current Opinion in Biotechnology. 20:692-699. (2009) (Of Record).
The teachings of Zhang from the previous art rejection is incorporated here in full.
Zhang does not teach a combination therapy comprising a PTPRS de-clustering agent of Fc fused to Ig1 and 2 and does not teach a dose for etanercept.
These deficiencies are filled by Bottini ‘554, Hoffmann, and Huang.
The teaches of Bottini ‘554, and Hoffmann from the previous rejections are incorporated here in full.
Huang teaches the use of Fc-fusions to another peptide (Figure 1 and Table 1). Huang teaches the use of Fc fusions in a number of patient populations including rheumatoid arthritis (Table 1). Huang teaches Fc fusions have improved pharmacokinetics with increased plasma-half-life wherein a biological active peptide maintains its activity while linked to the Fc domain (page 696 in col 1 in par 4-5). Huang specifically teaches Fc fusions can comprise an Fc fused to two different peptides and to receptor domains (Figure 1: b and d). Huang teaches the use of Fc fusions comprising anti-inflammatories including IL-1 inhibitors (Table 1).
It would have been obvious at the time the application was filed to combine the method of treating rheumatoid arthritis comprising etanercept and an anti-inflammatory agent taught by Zhang with the dosing for etanercept taught by Hoffmann, and the method of treating rheumatoid arthritis comprising the anti-inflammatory agent of and Fc fused to Ig1 and Ig2 taught by Bottini ‘554 in view of Huang. One of ordinary skill in the art would have been motivated to use art taught dosing for etanercept and an art taught anti-inflammatory. The substitutions of the general dose of Zhang with the specific dose of Hoffmann is obvious as Hoffmann provides effective doses for the treatment of rheumatoid arthritis which Zhang is teaching the treatment of. The substitution of the anti-inflammatory taught in combination with the etanercept of Zhang with the anti-inflammatory of Fc fused Ig1 and Ig2 of Bottini ‘554 would have been obvious as Bottini ‘554 teaches Ig1 and Ig2 as an anti-inflammatory that can be used in the treatment of rheumatoid arthritis. One of ordinary skill in the art would have been motivated to improve the serum half-life of the peptide of Bottini ‘554 to decrease dose amount and schedule and provide improved patient experience and outcomes when treating rheumatoid arthritis. There would have been a reasonable expectation of success as the fusion of an Fc domain is taught to improve outcomes for use on anti-inflammatory agents which is being taught by Bottini ‘554. The resulting combination therapy of etanercept with Fc fused Ig1 and Ig2 would have been expected to show improved clinical outcomes with improved patient experience as the Fc fusion would have increased plasma-half-life and longer biological activity resulting.
Applicant Arguments
Applicant argues the art rejection of the independent claim has been overcome rendering the dependent claims non-obvious.
Response to Arguments
Applicant's arguments filed 02/09/2026 have been fully considered but they are not persuasive.
Rejection of the independent claim is maintained.
Claims 1-5, 23-30, 32, 34, 36, and 38 are rejected under 35 U.S.C. 103 as being obvious over Zhang (WO 2019042170 A1) (Of Record), Bottini (WO 2014/018554 A1) (Of Record) (Hereafter “Bottini ‘554”), Hoffman (CA 2847142 C) (Of Record), Huang. Current Opinion in Biotechnology. 20:692-699. (2009) (Of Record), and Bottini (WO 2018/176019 A1)(Hereafter “Bottini ‘019”) (Of Record).
The applied reference has a common Applicant and Inventor 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).
The teachings of Zhang from the previous art rejections are incorporated here in full.
Zhang does not teach a combination therapy comprising a PTPRS de-clustering agent of Fc fused to Ig1 and 2 and does not teach a dose for etanercept.
These deficiencies are filled by Bottini ‘554, Hoffmann, Huang, and Bottini ’019
The teaches of Bottini ‘554, Hoffmann, and Huang from the previous rejections are incorporated here in full.
Bottini ’019 teaches the use of RPTP sigma Ig1 and Ig2 which is the peptide of Bottini ‘554 and the instant claims in a fusion with an Fc. Bottini ’019 teaches this fusion specifically inhibits rheumatoid arthritis FLS (Figure 2). Bottini ’019 teaches the treatment of rheumatoid arthritis ([0087]).
It would have been obvious at the time the application was filed to combine the method of treating rheumatoid arthritis comprising etanercept and an anti-inflammatory agent taught by Zhang with the dosing for etanercept taught by , and the method of treating rheumatoid arthritis comprising the anti-inflammatory agent of and Fc fused to Ig1 and Ig2 taught by Bottini ‘019 in view of Huang. One of ordinary skill in the art would have been motivated to use art taught dosing for etanercept and an art taught anti-inflammatory. The substitutions of the general dose of Zhang with the specific dose of Hoffmann is obvious as Hoffmann provides effective doses for the treatment of rheumatoid arthritis which Zhang is teaching the treatment of. The substitution of the anti-inflammatory taught in combination with the etanercept of Zhang with the anti-inflammatory of Fc fused Ig1 and Ig2 of Bottini ‘019 would have been obvious as Bottini ‘554 teaches Ig1 and Ig2 as an anti-inflammatory that can be used in the treatment of rheumatoid arthritis. One of ordinary skill in the art would have been motivated to use an anti-inflammatory with improved serum half-life and extended biological activity that Huang teaches the Fc fused to Ig1 and Ig2 of Bottini ‘019 would have. This would have been expected to decrease dose amount and schedule and provide improved patient experience and outcomes when treating rheumatoid arthritis. There would have been a reasonable expectation of success as the fusion of an Fc domain is taught to improve outcomes for use on anti-inflammatory agents and the fusion of Bottini ‘019 is an Fc fusion used as an anti-inflammatory. The resulting combination therapy of etanercept with Fc fused Ig1 and Ig2 would have been expected to show improved clinical outcomes with improved patient experience as the Fc fusion would have increased plasma-half-life and longer biological activity resulting.
In regards to the below therapeutically effective amount of TNF inhibitor required by all claims, specific dosage recited in the instant claims "[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), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal doses of treatment because optimal dose is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
This rejection under 35 U.S.C. 103 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); 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 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. See generally MPEP § 717.02.
Applicant Arguments
Applicant argues the art rejection of the independent claim has been overcome rendering the dependent claims non-obvious.
Response to Arguments
Applicant's arguments filed 02/09/2026 have been fully considered but they are not persuasive.
Rejection of the independent claim is maintained.
Rejection Maintained
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 1-3, 5, 10, 24-30, 32, 34, 36, and 38 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, and 7-16 of copending Application No. 18290679 (reference application) in view of Zhang (WO 2019042170 A1) (Of Record), Bottini (WO 2014/018554 A1) (Of Record) (Hereafter “Bottini ‘554), Hoffman (CA 2847142 C) (Of Record), and Huang. Current Opinion in Biotechnology. 20:692-699. (2009) (Of Record).
The reference application recites a pharmaceutical composition comprising the PTPRS agent of Ig1 or Ig2 for the treatment of autoimmune diseases (claims 1-3 and 7-8).
The reference application does not recite a TNF inhibitor of etanercept, the sequences of the claims, or the fusion of Ig1 or Ig2 as an Fc fusion.
These deficiencies are filled by Zhang, Hoffmann, Bottini ‘554, and Huang.
The teachings of Zhang, Hoffmann, Bottini ‘554, and Huang from the art rejections are incorporated here in full.
Bottini ‘554 teaches the use of Ig1 and Ig2 of the reference application in the treatment of rheumatoid arthritis as previously described.
Huang teaches the treatment of multiple autoimmune diseases including lupus (Tables 1-2).
It would have been obvious at the time the application was filed to combine the method of treating an autoimmune disease comprising the Ig1 and Ig2 domains of the reference application with the method comprising etanercept and an anti-inflammatory agent taught by Zhang and Hoffmann. The reference application teaches the treatment of autoimmune disease broadly while Bottini ‘554 teaches its use in rheumatoid arthritis patients. The substitution of the generic autoimmune diseases of the copending claims with the specific autoimmune disease of rheumatoid arthritis would have been obvious as Ig1 and Ig2 are used in the reference application and Bottini ‘554. There would have been a reasonable expectation of success as Bottini ‘554 teaches the peptide of the reference application used in the rheumatoid arthritis of Zhang and Hoffmann. Zhang teaches a method of treating rheumatoid arthritis comprising etanercept and an anti-inflammatory. The reference application in view of Bottini ‘554 recites an anti-inflammatory in a method of treating autoimmune diseases including rheumatoid arthritis. One of skill in the art would have been motivated to improve the method of treatment of the reference claims by combining it with etanercept as combination therapies show improved outcomes by interacting with multiple pathways.
One of skill in the art would have been further motivated to improve the anti-inflammatory peptide of Ig1 and Ig2 taught by the reference application and Bottini ‘554 with the use of an Fc domain as taught by Huang as Huang teaches the fusion of an Fc domain improves serum half-life and extends biological activity and further teaches its combination with on anti-inflammatory agents. The resulting combination therapy of etanercept with Fc fused Ig1 and Ig2 of the reference application would have been expected to show improved clinical outcomes with improved patient experience as the Fc fusion would have increased plasma-half-life and longer biological activity resulting.
In regards to the below therapeutically effective amount of TNF inhibitor required by all claims and the below therapeutically effective amount of the PTPRS de-clustering agent required by claims, specific dosage recited in the instant claims "[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), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal doses of treatment because optimal dose is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (ie dosage and intervals) optimization is obvious.
This is a provisional nonstatutory double patenting rejection.
Applicant Arguments
Applicant argues the overcoming of the art rejection of the independent claim has overcome this double patenting rejection and request the double patenting rejection be held in abeyance.
Response to Arguments
Applicant's arguments filed 02/09/2026 have been fully considered but they are not persuasive.
The art rejection is maintained as is the double patenting rejection.
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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