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 .
Status of the Claims
Claims 1-25 are pending.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Instant application is a U.S. National Stage Entry of PCT/GB2021/051600, filed 06/23/2021. PCT/GB2021/051600 claims priority of foreign application GB2009618.6, filed 06/24/2020. Therefore, the effective filing date is 06/24/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/31/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Restriction/Election Requirement
Applicant’s election without traverse of Group I, claims 1-17 and 19, in the reply filed on 11/18/2025 is acknowledged. Applicant further elected the necrosis pathway inhibitor dabrafenib (N-{3-[5-(2-aminopyrimidin-4-yl)-2-tert-butylthiazol-4-yl]-2-fluorophenyl}-2,6-difluoro-benzenesulfonamide).
Applicant’s elected species, dabrafenib, appears allowable in the method of treating FSHD. Therefore, according to MPEP 803.02: should the elected species be found allowable, the examination of the Markush-type claim will be extended. The examination of the Markush-type claims has been extended to include ponatinib. Since a nonelected species has been found not allowable, examination has been expanded to include claims directed to both the elected and nonelected species, and subject matter not embraced by the elected embodiment or the nonelected species is therefore withdrawn from further consideration. The elected species and nonelected species read on instant claims 1-9 and 19.
Claims 10-18 and 20-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/18/2025.
Objections – Drawings
37 C.F.R. 1.84
(u) Numbering of views.
(1) The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear.
The drawings are objected to because the views are not preceded by the abbreviation “FIG.”, and the partial views are not identified by “FIG.” and the view number with the corresponding capital letter (e.g., “FIG. 1A”, “FIG. 1B”).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 9 is objected to because of the following informalities:
In claim 9, the compound name for HS-1371 reads “Quinoline, 4-(4-methylphenoxy)-7-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-”, and should read “4-(4-methylphenoxy)-7-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-quinoline”.
Appropriate correction is required.
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.
Claims 1-9 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating FSHD comprising administering an effective amount of galavit, dabrafenib, or a DUX4 inhibitor listed in claim 9, does not reasonably provide enablement for a method of treating FSHD comprising administering any amount of any inhibitor of the necroptosis pathway. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
Breadth of the claims
The breadth of the claim includes a method of treating FSHD, comprising administering any inhibitor of the necroptosis pathway.
Nature of the invention
The nature of the invention is performance of a method of treating FSHD, comprising administering any inhibitor of the necroptosis pathway.
State of the prior art
DUX4 is known in the prior art to play a role in the treatment of FSHD (WO 2019084499 A1). The prior art does not teach that any compound capable of inhibiting the necroptosis pathway, inclusive of the inhibition of any gene or protein that may play a role in this pathway, as stated in the instant claims, is also capable of treating FSHD. Known inhibitors of DUX4, discussed in WO 2019084499 A1, have been shown to be useful in the treatment of FSHD.
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of treating FSHD in a patient, comprising administering an inhibitor of the necroptosis pathway, would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
Level of predictability in the art
Synthetic organic chemistry is quite unpredictable. See In re Marzocchi and Horton 169 USPQ at 367 ¶3. Similarly, it is well established that “[T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Amount of direction provided by the inventor
The invention lacks direction with respect to making and/or using (performing) a method of treating FSHD in a patient, comprising administering an inhibitor of the necroptosis pathway. Limited examples are provided for compounds reading on the inhibitor of the necroptosis pathway, and at best, an effective amount of such inhibitors is described in the specification, on page 15, as an “amount of compound which is sufficient to provide a beneficial effect to the subject to which the compound is administered.” Additionally, the administration of an effective amount of said compounds is not required by the instant claims, and no direction is provided in the claims or specification as to how one would determine what an effective amount is for each potential inhibitor.
Existence of working examples
The disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating FSHD in a patient, comprising administering an inhibitor of the necroptosis pathway.
Similarly, according to the specification, any compound that inhibits the necroptosis pathway is capable of treating FSHD.
However, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with the scope of the claims. The specification only provides examples for treating FSHD comprising administering galavit and dabrafenib. There is insufficient disclosure to reasonably conclude that the method of treating FSHD in a patient, comprising administering any compound that inhibits the necroptosis pathway, as recited, would contribute to treatment of FSHD. The inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claim.
Quantity of experimentation needed
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
One skilled in the art, such as a medical doctor, would be required to perform hundreds of clinical trials and in vivo or in vitro assays in order to determine which of the indefinite number of inhibitors would be capable of treating FSHD. Even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for a method of treating FSHD in a patient, comprising administering an inhibitor of the necroptosis pathway, is clearly justified.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation of a list of small molecule inhibitor compounds, and the claim also recites “optionally wherein the inhibitor is…”, followed by a repetition of some compounds from the broader list, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The inventor or joint inventor should note that claim 1 is a reach-through claim. The claim attempts to obtain protection for subject matter that is prophetic and/or has yet to be invented. This includes both inhibitors of the necroptosis pathway have not yet been invented, as well as targets (e.g., proteins, genes) capable of being inhibited by compounds that would result in the inhibition of the necroptosis pathway that have not yet been identified. Similarly, the metes and bounds of the inhibitors of the necroptosis pathway are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. Neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. The inhibitor is only defined, in claims 1-8 and 19, by its desired function. Consequently, the method for the treatment of FSHD, the method comprising administering “an inhibitor of the necroptosis pathway” has been rendered indefinite by the use of the reach-through protocol. Dependent claims 2-8 and 19 are rejected as being dependent upon a rejected claim and failing to give structure to the inhibitor of the necroptosis pathway.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-9 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rickard et al. (WO 2019084499 A1), cited by Applicant in the IDS.
Rickard et al. teaches methods of treating FSHD. Rickard et al. teaches, in paragraph [00117], “in some embodiments, the compound used to treat subjects with muscular deficiencies such as FSHD is ponatinib, or analogs or salts thereof”, as in instant claims 1, 7-9, and 19. Ponatinib is taught, in paragraph [00114], to block activation of DUX4, which is known to trigger necroptosis through the RIPK3–MLKL pathway, as in instant claims 2-4. Example 5 shows that the method is administered to myotubes and myoblasts, as in instant claim 6.
It is taught in paragraph [0055] that the method results in up to a 100% decrease in DUX4 expression, as in instant claim 5. Additionally, MPEP 2112 I states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).” In other words, products of identical or similar composition (in the instant case, compositions for the treatment of FSHD comprising ponatinib) cannot exert mutually exclusive properties when administered under the same or similar circumstances.
Nonstatutory 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 1-7 and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17, and 18 of U.S. Patent No. 10,385,338 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Patent ‘338 teaches, in claims 1, 17, and 18, a method of treating FSHD comprising administering a viral vector that inhibits DUX4, which is known to trigger necroptosis through the RIPK3–MLKL pathway, as in instant claims 1-4, 7, and 19. Regarding instant claim 5, the inhibition would be an inherent property of the method of the prior art. See MPEP2112 I. Alternatively, the inhibition and administration technique of claims 5 and 6 would be considered routine optimization of the method taught by Patent ‘338. See MPEP 2144.05.
Conclusion
Claims 1-9 and 19 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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