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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/10/25 has been entered.
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 1 remains and claim 48 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claimed method reads on using a SOS2 nucleic acid inhibitor to treat intra-ocular (IOP) pressure or glaucoma in a human patient.
The prior art of record appears to disclose that a predicted loss of function variant recited in the instant claims were not known to be associated with an ophthalmic condition. Pierre et al. (Biochemical Pharmacology 82, 1049-1056, 2011, cited on an IDS) teach, "Understanding why only SOS1 mutation (but not SOS2 mutations) have been found in association with human pathologies (page 303)." Rojas et al. (Genes & Cancer 2: 293-305, 2011, cited on an IDS) disclose that a heterozygous mutation in SOS2 causes Noonan Syndrome. Noonan syndrome is a genetic condition that stops typical development in various body parts.
The specification does not provide a working example of the claimed method. The specification contemplates the method. The only working example listed in the specification is directed to exome sequence analysis that shows that two missense variants (Pro191Arg and Ala208Thr) are associated with IOP (Figure 1A and 1B), glaucoma (Figures 2A and 2B) and AST (figure 3). Both variants were associated with a reduced risk for glaucoma. In view of this example it appears that a skilled artisan would want to study increasing the missense SOS2 variants and not inhibit SOS2 expression. A missense mutation can be a loss-of-function mutation, but the mutation does not always result in a loss-of-function. It can lead to a complete or partial loss of function, a neutral effect, or even a gain of function, depending on where the mutation occurs and how the new amino acid changes the protein's structure. Like biomarkers, genetic analysis helps identify genes that may contribute to an individual's risk for glaucoma or IOP similar.
It appears that the specification is trying to extrapolate from the working example to using SOS2 as a biomarker for ophthalmic conditions and/or target for treating the conditions. The discovery and application of glaucoma biomarkers can be difficult, the maker selection is limited by patients with individual differences, techniques for the use and analysis of therapeutic drugs. See Agnifili et al. Prog. Brain Res. 2015, 221, pages 1-32, cited on an IDS.
Furthermore, other than contemplating the claimed method and one example directed to expression of SOS2 in unknown samples, the specification of the application does not disclose how to use the claimed invention without an undue amount of experimentation. See MPEP 2164.05(a) Specification must be enabling as of the filing date. See also Genentech Inc. V. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: "Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner V. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention." Thus, in view of the reasons set forth above, it would take an undue amount of experimentation for one of skill in the art to practice the claimed invention.
Thus, claims 1 and 48 are not enabled.
Response to Arguments
Applicant's arguments filed 12/10/25 have been fully considered but they are not persuasive.
Applicant argues that applicant believes that the Office might have miscomprehended that disclosed data or mischaracterized the data because the specification discloses that the missense variants are putative loss of function variants that reduce risk for IOP and glaucoma and a skilled artisan would conclude that reducing SOS2 expression by administering an SOS2 inhibitor treats IOP and glaucoma.
Applicant's arguments is not found persuasive because "putative loss of function variant" indicates that it is assumed to be a loss of function but as stated in the enablement rejection, and incorporated herein, there is nothing of record to indicate that reducing SOS2 expression in the eye of a subject having an eye disorder (IOP or glaucoma) would result in treating the disorder. Without a skilled artisan experimenting with the method to determine if the biomarker is also a therapeutic target, the claimed invention is not considered enabled. Thus, at the time of filing, the treatment method was not considered enabled. Furthermore, paragraph 49 of the specification discloses that for human subjects or patients that are genotyped or determined to be either SOS2 reference or heterozygous for an SOS2 predicted loss-of-function variant, such human subjects or patients can be treated with an SOS2 inhibitor. The claimed method is broader than this teaching in the specification.
In response to applicant's argument that the specification provides enablement for the claimed method because the specification discloses sequencing and analysis of an extensive data set of 145,000 genetic patient samples and identifies rare missense mutations as linked to IOP and glaucoma, the argument is not found persuasive because a missense mutation can be a loss-of-function mutation, but it isn't always. It can lead to a complete or partial loss of function, a neutral effect, or even a gain of function, depending on where the mutation occurs and how the new amino acid changes the protein's structure. Like biomarkers, genetic analysis helps identify genes that may contribute to an individual's risk for glaucoma or IOP similar. The specification does not provide a working example of the claimed invention.
Furthermore, the expression of SOS2 is from unknown samples. What tissue (eye, serum, blood, liver) was being analyzed?
In response to applicant's argument that the reference cited by the Office is more than a decade old and seems primarily focus on molecular biomarkers which unlike the genetic association analysis provided in the present application, the argument is not found persuasive because the age of the reference is moot because it discusses unpredictability (undue amount of experimentation) of correlating a biomarker to a therapeutic target that and there appears no art of record to indicate that that issue has changed in the past ten years. The specification appears to disclose that two missense mutations are associated with reduced IOP and reduced risk of glaucoma. Reduced risk does not indicate that the subject will have glaucoma. It just indicates that the subject might not experience glaucoma if they have the missense SOS variant.
Thus, the claimed method is not considered enabled
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, 8, 10, 45-47 remain and claim 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11820982, of record. Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims embrace treating an ophthalmic condition in a human patient comprising measuring a SOS2 nucleic acid molecule in the patient from the a biological sample from the patient, performing a genotype assay on the sample, determining if the patient has a SOS2 variant nucleic acid molecule encoding SOS2 Pro191Arg (isoform 1 or 2), Ala208Thr (isoform 1 or 2), and administering a known ophthalmic agent to the patient and administering a SOS2 inhibitor selected from a siRNA, shRNA or a quianzoline. The sequences set forth in the instant claims are the same sequences set forth in the claims of '982 patent. Thus, the instant claims appear to be an obvious variant of the claims of '982.
Response to Arguments
Applicant's arguments filed 11/10/25 have been fully considered but they are not persuasive because applicant did not argue the merits of the NSDP rejection. It is noted that applicant request that the rejection be held in abeyance until allowable subject matter has been identified.
As stated in the 112a rejection, claims 1, 8, 10, and 45-48 are free of the prior art. The method in new claim 49 can be used to study decreasing SOS2 polypeptide expression in a cell of a human subject having increased IOP or glaucoma. The prior art does not teach or suggest decreasing SOS2 polypeptide expression in a cell of a human subject having increased IOP or glaucoma. In addition, while the claimed method of treating IOP or glaucoma in the human subject using an antisense or siRNA that comprises a sequence that is complementary to a SOS2 mRNA is not considered enabled, the additional method step of using a known therapeutic agent for glaucoma or IOP is enabled. Nothing in the prior art teaches that reducing SOS2 expression in the human subject would interfere with the known therapeutic agent. Thus, the combination of the known agent in the method step is considered enabled.
Conclusion
See attached PTO-326 for disposition of claims.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636