DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Preliminary amendment filed on 09/14/2023 has been entered. Claims 10-12, 14-16, 20, 23, 24, and 26-28 are cancelled. Claims 31 and 32 are new. Claims 1-9, 13, 17-19, 21, 22, 25, and 29-32 are pending in this application. Claims 3-9, 22, 25, and 29-32 are withdrawn. Claims 1, 2, 13, 17-19 and 21 are currently under examination.
Priority
This application is a 371 of PCT/US2022/020362 filed on 03/15/2022 and claims benefit of US PRO 63/161,050 filed on 03/15/2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed application, Application No. 63/161,050, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 1, 2, 13, 17-19 and 21 recite “
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”, which are not disclosed or supported by the prior-filed Application No. 63/161,050. Thus, the priority date of claims 1, 2, 13, 17-19 and 21 is 03/15/2022.
Election/Restrictions
Applicant's election with traverse of Group I invention (claims 1-9, 13, 17-19, 21, and 31) and species (A. ataxia-telangiectasia as the specific disease; and B. censavudine as the specific LINE-1 inhibitor) in the reply filed on 04/24/2026 is acknowledged. The traversal is on the ground(s) that “the instant application do not qualify as a "clear case" of lacking unity of invention… a search of Group I would not impose a serious burden upon the Examiner… the kit of Group II, which comprises the same compounds and recites the same diseases those recited in Group I” (p. 2, para. 3), and “a search of the elected species would likely uncover art of interest to other species recited in the instant claims. Any additional searches that would be needed would not be an undue burden on the Examiner” (p. 3, para. 2). This is not found persuasive because "Groups I/II are directed to a technical feature: censavudine. This technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Sedivy et al. (WO2020154656, published on 07/30/2020, also listed in IDS filed on 09/19/2024), who teach that inhibition of human L1 activity with Censavudine… Therefore, the technical feature of Groups I/II cannot be a special technical feature over the prior art” and “the species listed in Groups A to B do not share either common activities or common structures”, as set forth on pages 5 to 6 of the Restriction/Election Requirement mailed on 02/26/2026. “Lack of unity of invention may be directly evident “ a priori ,” that is, before considering the claims in relation to any prior art, or may only become apparent “ a posteriori ,” that is, after taking the prior art into consideration. For example, independent claims to A + X, A + Y, X + Y can be said to lack unity a priori as there is no subject matter common to all claims. In the case of independent claims to A + X and A + Y, unity of invention is present a priori as A is common to both claims. However, if it can be established that A is known, there is lack of unity a posteriori, since A (be it a single feature or a group of features) is not a technical feature that defines a contribution over the prior art.“ (see MPEP § 1850 [R-01.2024], 37 CFR 1.475, II).
Claims 3-9, 22, 25, and 29-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 1, 2, 13, 17-19 and 21 are currently under examination.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 09/19/2024, 01/16/2025, 04/24/2026 with appropriate assertion under 37 CFR 1.98 have been considered.
Claim Objections
Claims 17, 18, and 21 are objected to because of the following informalities: In claims 17 and 18, insert the missing phrase “, wherein the method is” immediately after the recitation “of claim 1” (line 1) to become a proper dependent claim. In claim 21, change the incorrect conjunction “and/or” (line 3) to “or” because the (a), (b), and (c) cannot coexist. 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, 2, 13, 17-19 and 21 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 reducing or ameliorating a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof, does not reasonably provide enablement for treating or preventing a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof. The term “treating” is defined “As used herein, the terms "treat," "treating," "treatment," and the like refer to eliminating, reducing, or ameliorating a CNS or systemic disease and/or symptoms associated therewith” and the term “preventing” is defined “As used herein, the terms "prevent," "preventing," "prevention" and the like refer to a method of preventing the onset of a CNS or systemic disease and/or symptoms associated therewith”, in the specification (p. 21 to 22, [0101 and 0102]). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or to use the invention commensurate in scope with these claims. Claims 2, 13, 19 and 21 depend from claim 1.
Applicants claim a method of treating or preventing a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof recited in claims 1, 17, and 18, which encompass “eliminating” and “preventing the onset” the recited disease. In the absence of a limiting definition by the Applicants, "prevention" as described according to the Institute for International Medical Education (pages 15 and 16), is a preventive measure, such as preserving physical fitness in primary prevention and effective intervention to correct departures from good health in secondary prevention. More specifically, tertiary prevention, which is most relevant as used in the context of the instant invention, "consists of the measures available to reduce or eliminate long-term impairments and disabilities, [and to] minimize suffering caused by existing departures from good health". Thus, the claimed method of preventing a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof as interpreted by a skilled practitioner of the medical or pharmaceutical arts would be to reduce for long-term the occurrence of or to eliminate a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof by the method.
The Applicant's attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The rejected invention is drawn to A method of treating or preventing a disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a LINE-1 inhibitor, or a pharmaceutical composition thereof, wherein the disease is ataxia-telangiectasia, age-related macular degeneration, systemic lupus erythematosus, IFN-associated autoimmune disease, Fanconi Anemia, idiopathic pulmonary fibrosis, or cardiovascular disease, and the LINE-1 inhibitor is censavudine,
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(claims 1, 17, and 18).
Relative skill of those in the art: The relative skill of those in the art is from biomedical field (see the cited reference below).
Breadth of claims: The claim is extremely broad in that it encompasses the elimination or prevention of a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof using the claimed method.
State of the prior art/Predictability or unpredictability of the art: There is no teaching or suggestion in the state of the prior art that application of certain pharmaceutical method can eliminate or prevent a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof. Dumitrache et al. (Neuron 110, October 19, 2022, 3217-3219) disclosed that in brain, abnormal activation of long interspersed nuclear element 1 (LINE-1, L1) is linked to neurodevelopmental defects, neuroinflammation, and neurodegeneration. One such syndrome to which L1 activity has been previously linked is ataxia telangiectasia (AT). To validate that L1 upregulation was the cause of the cerebellar degeneration in the LINE-1a mouse brain, the mice were treated with nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs such as 3TC (= Lamivudine) have been shown to inhibit L1 reverse transcriptase (and TEs in general) and are currently in trial for some neurodegenerative diseases. These data show that suppressing L1 expression can decrease the DNA damage and neuroinflammation and slow the PC degeneration and ataxia associated with L1 overexpression (page 3217, left col., para. 1; page 3218, left col., para. 2; middle col., para. 1). One of skilled artisan would understand that contemporary treatment or management of ataxia telangiectasia is to minimize ataxia telangiectasia symptoms, not to eliminate or to prevent, ataxia telangiectasia.
Amount of guidance/Existence of working examples: It is worth noting that there are no working examples in the instant application to show that the claimed method is effective for eliminating or for preventing a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof as recited in the claim. The exemplary embodiments of the Specification merely present in vitro assays: Islatravir and other compounds were tested for inhibition of retrotransposition activity of human LINE-1 in HeLa cells. The results are provided in Table 3 and Table 4 in Example 1 (p. 34-37).
Quantity of experimentation: In order to practice the full scope of the invention, one skilled in the art would need to undertake a novel and extensive research program to show that a disease-eliminating or preventive measure can be achieved after applying the claimed method. Furthermore, one of ordinary skill in the art would need to test a representative number of animals before one of ordinary skill in the art would be able to conclude that any method can be used to eliminate or to prevent a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof. Because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope of use in eliminatiion or prevention of a disease, wherein the disease is ataxia-telangiectasia (elected), in a subject in need thereof, it would constitute an undue and unpredictable experimental burden.
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164. Genetech, 108 F.3d at 1366, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent 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".
Therefore, in view of the Wands factors as discussed above, including the amount of guidance provided and the predictability of the art and the lack of working examples to practice the full scope of the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 21 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 21 recites the limitation "the HIV" (lines 2 to 3, a total of 3 occurrences). There is insufficient antecedent basis for this limitation in the claim. Applicant is advised to change the above recitation to “an HIV”.
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.
(I) Claims 1, 2, 13, 17-19 and 21 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Romero et al. (WO 2023/164472, published on August 31, 2023 and benefitted from US PRO 63/312,472 filed on February 22, 2022, hereinafter referred to as Romero ‘472).
With regard to structural limitations “a method comprising administering to a subject suffering from a disease (and not infected with an HIV virus) a therapeutically effective amount of a LINE-1 inhibitor, or a pharmaceutical composition thereof (or further comprising administering one or more optional therapeutic agents), wherein the disease is ataxia-telangiectasia (elected), and the LINE-1 inhibitor is censavudin (=
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, elected)” (claims 1, 2, 13, 17-19 and 21):
Romero ‘472 disclosed a method for treating medical disorders, such as cancer, autoimmune disorders, and/or neurological disorders, and modulating LINE1 reverse transcriptase and/or HERV-K reverse transcriptase using censavudine or a related compound. The compounds may be part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier. As used herein, "censavudine" refers to 1-[(2R,5R)-5-ethynyl-5-(hydroxymethyl)-2H-furan-2-yl]-5-methylpyrimidine-2,4-dione, which is the chemical entity represented by the structure:
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. In certain embodiments, the method further comprises administering an effective amount of an additional therapeutic agent. In certain embodiments, the autoimmune disorder is selected from Aicardi-Goutieres syndrome, rheumatoid arthritis, psoriasis, systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), graft versus host disease, scleroderma, type I diabetes, dermatomyositis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, vasculitis, and Sjogren's syndrome (page 5/67, [0015]; page 11/67, [0037]; page 20/67, [0070]). LINE-1 has also been implicated in neurological disorders such as ataxia telangiectasia (AT) and Rett syndrome (Zhang, 2020). The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes (page 4/67, [0011]; page 50/67, [0210]).
Thus, these teachings of Romero ‘472 anticipate Applicant’s claims 1, 2, 13, 17-19 and 21.
(II) Claims 1, 2, 13, 17-19 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sedivy et al. (WO 2020/154656, published on July 30, 2020, hereinafter referred to as Sedivy ‘656, also listed in IDS filed on 09/19/2024) incorporated by Erwin et al. (Nat. Rev. Neurosci. 15, 497-506, 2014, hereinafter referred to as Erwin ‘2014, also listed in IDS filed on 09/19/2024).
With regard to structural limitations “a method comprising administering to a subject suffering from a disease (and not infected with an HIV virus) a therapeutically effective amount of a LINE-1 inhibitor, or a pharmaceutical composition thereof (or further comprising administering one or more optional therapeutic agents), wherein the disease is ataxia-telangiectasia (elected), and the LINE-1 inhibitor is censavudin (=
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, elected)” (claims 1, 2, 13, 17-19 and 21):
Sedivy ‘656 disclosed a method for treating or reversing age-associated inflammation in a patient in need thereof comprising administering a therapeutically effective amount of a reverse transcriptase inhibitor (RTI) to the patient in need thereof, wherein the RTI comprises censavudine or elvucitabine. The only human retrotransposable element (RTE) capable of autonomous retrotransposition is the long-interspersed element-1 (LINE-1, or L1). Increasing evidence points to RTE activation in some cancers, in the adult brain, and during aging (ref # 117, 118, 119, 120). In addition, the RTI and the at least one second therapeutic agent can be administered from a single composition or two separate compositions (page 44/151, [0158]; page 61/151, [0192]; page 40/151, [0140]). All patents, patent application, and publications cited herein are fully incorporated by reference herein. Erwin, J.A., et al. (2014). Mobile DNA elements in the generation of diversity and complexity in the brain. Nat. Rev. Neurosci. 15, 497-506 (page 97/151, [0233]; page 95/151, line 1 to 2). Erwin ‘2014 (incorporated by reference here) disclosed that there are increased rates of retrotransposition in mouse and human models of Rett syndrome and ataxia telangiectasia. Another disorder associated with increased somatic retrotransposition, ataxia telangiectasia, is a neurodegenerative disorder caused by mutations in the gene encoding ataxia telangiectasia mutated (page 499, right col., para. 1; page 504, left col., para. 2).
Thus, these teachings of Sedivy ‘656 incorporated by Erwin ‘2014 anticipate Applicant’s claims 1, 2, 13, 17-19 and 21.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
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