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 Claims
The amendments to the claims filed October 28, 2024 are acknowledged and entered. Claims 1-15 are pending.
Priority
This application is a 371 of PCT/EP2023/057044, filed March 20, 2023, which claims priority of EP22305333.1, filed March 21, 2022.
Information Disclosure Statement
Acknowledgement is made of the Information Disclosure Statement filed on October 28, 2024. All references have been considered except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification.
Claim Rejections - 35 USC § 112a
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 1-15 are 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.
The claims are drawn to a method of inhibiting senescence in a subject. The claims require administration of an a “SHP2 inhibitor”; however, the claims do not require that the “SHP2 inhibitor” possess any particular conserved structure, or other distinguishing feature. The specification provides some examples of SHP2 inhibitor compounds, however, there is no complete description of compounds embraced by this genus. Moreover, the state of the prior art recognizes that that this class of compounds may be used to induce senescence. Lan et al. (EMBO Journal 2015, 34, 1493-1508) teaches senescence induction leads to the inhibition of self-renewal of tumor cells and the blockage of tumor growth and formation. Senescence induction by inhibiting SHP2 may be useful for blocking cancer (Abstract). Applicant teaches SHP2 inhibitors are well known in the art (page 6); however, it appears that at least some SHP2 inhibitors are known to have the opposite effect of that which is claimed. Given the direction provided by Applicant, one skilled in the art would not recognize that Applicant was in possession of the invention as claimed at the time the application was filed.
It is suggested that the claims be amended to recite specific SHP2 inhibitors for which Applicant has written support in their specification.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 [10 USPQ2d 1614] (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”). Thus, an applicant complies with the written-description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572.
According to the MPEP §2163 I. A. “the issue of a lack of adequate written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant had possession of the claimed invention. The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.” The MPEP states in §2163 II 3 ii) “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 (see i)(A), above), reduction to drawings (see i)(B), above), or 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 (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
According to the MPEP §2163.02 Standard for Determining Compliance With the Written Description Requirement,
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed". In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter". Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
Applicants are reminded of what the U.S. Court of Appeals Federal Circuit wrote in University of California v. Eli Lilly and Co. 43 USPQ2d 1398, "In claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus." "A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is.” See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). "It is only a definition of a useful result rather than a definition of what achieves that result." "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.")".
Claims 1-2, 4 and 6-9 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 a condition which the state of the prior art recognizes may be treated by administration of an SHP2 inhibitor and for which Applicant has written support does not reasonably provide enablement for inhibiting senescence generally in a subject. 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.
In evaluating the enablement question, several factors are to be considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed. 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.
The nature of the invention & breadth of claims:
Claim 1 is drawn to a method of inhibiting senescence in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a SHP2 inhibitor.
Claims 2 depends from claim 1 and recites wherein the subject is elderly.
Claim 4 depends from claim 1 and recites wherein the subject is suffering from a physiological change accompanying senescence selected from the group consisting of physical endurance, fatigue, decrease in energy metabolism, and dysfunction of mitochondria.
Claim 6 depends from claim 1 and recites wherein the subject is suffering from an age-associated disease.
Claim 7 depends from claim 6 and recites specific diseases including classes of diseases represented by a neurodegenerative disease and a chronic inflammatory disease. Claim 8 depends from claim 6 and requires that the disease is associated with inflammation.
Claim 9 depends from claim 1 and requires that the SHP2 inhibitor is conjugated to a nanoparticle.
The specification teaches conditions embraced by the claims refers to any disease or condition in a mammalian, preferably human, subject wherein the presence of senescent cells, or presence of
cellular senescence, or presence of senescence, in a mammalian, preferably human, subject is linked to said disease or condition in said subject (see page 4, “age associated disease”). State of the prior at reference Kirkland et al. (Journal of Internal Medicine 2020, Vol 288, 518-536) teaches senolytics are a class of drugs that selectively clear senescent cells. Senescent cells are selectively target from amongst normal cell types, leading to the death of senescent cells and treatment of age-related disease (Graphical Abstract). Broadly, the claims only require administration of an SHP2 inhibitor which is generally known in the art for the treatment of different forms of disease (see art rejections set forth herein).
In view of the specification and state of the prior art, a person skilled in the art would understand the claimed invention to be a method of treating a disease by administration of an SHP2 inhibitor. The method would be understood to be useful for treating conditions for which senolytics are believed to be useful and also of conditions believed to be treatable with an SHP2 inhibitor. Claims 1-2, 4, 6 and 9 do not recite any disease and therefore very broadly include any form of disease. Claims 7-8 include broad classes of disease such as chronic inflammatory and neurodegenerative disease. The claimed method of treatment is very broad.
The state of the prior art
State of the prior at reference Kirkland et al. noted above teaches in preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular disease, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment. Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer’s disease, COVID-19, osteoarthritis, and other conditions are underway or beginning (Abstract). See also Table 2, which recites specific conditions believed to potentially benefit from senolytics. The state of the prior art appears to recognize the claimed method may have use in the treatment of some conditions embraced by the claims (e.g. Alzheimer’s) but is unaware the method may have use as a general treatment of all disease as is presently claimed.
Regarding SHP2 inhibitors, the state of the prior art does not recognize that this class of compounds broadly treats all forms of disease as is presently claimed. Nor does the prior art recognize that an SHP2 inhibitor broadly treats all forms of neurodegenerative disease (see references Miller et al. (WO2021/119525), Jorand-Lebrun et al. (WO2020/210384), Feng et al. (WO2005/094314) and Yart et al. (WO2020/104635) provided in the art rejections set forth below).
The Level of One of Ordinary Skill
The level of skill in the art is high. The artisan using the claimed invention would be a person with medical training such as a medical doctor or physician with an MD degree or the equivalent.
Predictability in the art
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Amount of guidance/working examples
Applicant demonstrates that compounds of the invention inhibit senescence in a mouse model (See Example at pages 17-18).
No examples are provided to show the claimed method may treat any particular disease.
The quantity of experimentation needed:
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on theevidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
That conclusion is clearly justified here and one skilled in the art could not practice the full scope of the claimed invention without undue experimentation.
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.
Claims 1, 6-8 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (WO2015/003094)(hereinafter “Zhang”).
Regarding claim 1, Zhang teaches a method of administering an SHP2 inhibitor to a subject in need thereof (see claim 7). Regarding “inhibition of senescence”, this limitation appears to be the biological result or consequence of administration of an SHP2 inhibitor. The prior art teaches the claimed method step of administering an SHP2 inhibitor and therefore the downstream biological effects that result from this administration would be intrinsic to the prior art method. Providing an explanation for how the prior art method may work is not a limitation which distinguishes the instant method from the prior art.
Regarding claims 6-8 and 15, Zhang teaches wherein the method of administering an SHP2 inhibitor treats a chronic inflammatory condition (see claim 11; systemic lupus erythematosus). As evidenced by Marczynski et al. (Int. J. Mol. Sci. 2021 22(5) Abstract), systemic lupus erythematosus is a chronic inflammatory disease.
Zhang teaches the claimed limitations and therefore anticipates the instant invention.
Claims 1-4, 6-7 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yart et al. (WO2020/104635)(hereinafter “Yart”).
Regarding claims 1, 3 and 6-7, Yart teaches administration of a SHP2 inhibitor to a subject for the treatment of diabetes and obesity (claims 1-3)
Regarding claims 2 and 4, Yart teaches subject refers to an individual and “individual” does not denote a particular age and includes adults (page 2). Elderly subjects are adults. Metabolism is known to decrease with age.
Regarding claim 9, Yart teaches the SHP2 inhibitor is embedded or conjugated to a nanoparticle,
so that the SHP2 inhibitor would be preferentially deliver in myeloid cells (e.g. macrophages) that are able to phagocyte said nanoparticle (page 11).
As mentioned above, Applicant’s mechanism “inhibiting senescence” would necessarily be included as it is the result of administering an SHP2 inhibitor. Yart teaches the claim limitations of administration of an SHP2 inhibitor to a subject and claimed diseases and therefore anticipates the claimed invention.
Claims 1, 5-7 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feng et al. (WO2005/094314)(hereinafter “Feng”).
Feng teaches a composition comprising an SHP2 inhibitor that may be administered to a subject for the treatment of cachexia (claims 15-18; page 9). Feng teaches cachexia is characterized by muscle loss (page 4). The instant specification teaches senescence is the gradual deterioration of functional characteristics (page 3). Muscle loss is regarded as including loss due to muscle senescence. Feng teaches the composition may be administered using a nanoparticle (page 4)
As mentioned above, Applicant’s mechanism “inhibiting senescence” would necessarily be included as it is the result of administering an SHP2 inhibitor. Feng teaches the claim limitations of administration of an SHP2 inhibitor to a subject and claimed diseases and therefore anticipates the claimed invention.
Claims 1, 6-8, 10 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jorand-Lebrun et al. (WO2020/210384)(hereinafter “Jorand-Lebrun”).
Jorand-Lebrun teaches compounds that are highly effective SHP2 inhibitors (page 4, Summary of the invention). Jorand-Lebrun teaches the compounds may administered to a subject in the treatment of age-related macular degeneration, chronic inflammatory disorders and arthritis (page 36, lines 30-35; page 37, lines 1-15).
As mentioned above, Applicant’s mechanism “inhibiting senescence” would necessarily be included as it is the result of administering an SHP2 inhibitor. Jorand-Lebrun teaches the claim limitations of administration of an SHP2 inhibitor to a subject and claimed diseases and therefore anticipates the claimed invention.
Claims 1-2, 4, 6-8, 11 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Miller et al. (WO2021/119525)(hereinafter “Miller”).
Miller teaches a method of treating a neurodegenerative disorder including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, or chronic inflammatory demyelinating polyneuropathy comprising administering a subject and effective amount of and SHP2 inhibitor (claims 5-7). Miller teaches wherein the disorder is one resulting from exposure to mitochondrial toxins ([00023]). A disorder resulting from exposure to mitochondrial toxins would presumably include dysfunction of mitochondria. Miller teaches the subject is an elderly subject (see [000146] adult subject e.g. senior adult).
As mentioned above, Applicant’s mechanism “inhibiting senescence” would necessarily be included as it is the result of administering an SHP2 inhibitor. Miller teaches the claim limitations of administration of an SHP2 inhibitor to a subject and claimed diseases and therefore anticipates the claimed invention.
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.
Claim 1 and 6-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/809,948 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipate by the reference claims.
Reference claim 1 recites:
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In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See also Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008);Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). The specification of the reference application teaches the method is particularly suitable for the treatment of type 2 diabetes (page 2).
The reference claims do not recite Applicant’s mechanism of “inhibiting senescence”; however, as has been noted above, Applicant’s mechanism would necessarily be included as it is the result of administering an SHP2 inhibitor.
The reference claim teaches the required limitation of administration of an SHP2 inhibitor and embraces a treatment of a diabetes as is presently claimed by the instant application. The instant claims are therefore anticipated by the reference claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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October 1, 2026
/K.S.M./Examiner, Art Unit 1624
/BRUCK KIFLE/Primary Examiner, Art Unit 1624
