DETAILED ACTION
This office action is in response to applicant’s filing dated October 2, 2025.
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
Claims 1-20 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed October 2, 2025.
Election/Restrictions
Applicant’s election without traverse of Group II, drawn to a method of inhibiting Cytosine-phosphate-Guanine negative (CGI-) gene misexpression in a cell comprising administering an effective amount of a BET inhibitor to the cell in the reply filed on October 2, 2025 is acknowledged.
The Examiner notes that Applicant presents arguments with regard to the lack of unity. In the interest of compact prosecution, the Examiner is addressing the traversal arguments. However, Applicants must clarify in their next response if the election was with or without traverse.
The traversal is on the ground(s) that Bradner is directed to broad categories of diseases, namely, neoplasia, inflammatory disease, obesity, fatty liver disease, diabetes, atherosclerosis, arterial stent occlusion, heart failure, and other disorders; the mechanism of action that Bradner describes is to inhibit BET proteins by binding to a bromodomain structural binding pocket; as a result, such BET inhibitor compounds are thought to inhibit the growth, proliferation, or survival of proliferating neoplastic cells or of inducing the differentiation of such cells. However, Bradner fails to describe the inhibition of cytosine-phosphate-guanine negative (CGI-) gene misexpression as claimed (claim 12). Applicant also notes that Bradner does not describe treating the elected species, Alzheimer's disease.
This is not found persuasive because the examiner notes that Group I was directed to a method of treating a subject suffering from an age-related inflammatory disease in a subject comprising administering a therapeutically effective amount of a Bromodomain and ExtraTerminal (BET) domain inhibitor to the subject in need thereof. Thus, Group I did not require inhibition of cytosine-phosphate-guanine negative (CGI-) gene misexpression. Neither group required a subject having Alzheimer’s. Thus, these limitations do not make up part of the special technical feature as they are not shared between groups or species. As set forth previously, Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of a BET inhibitor, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Brander (US 2013/0184264 A1, cited in the IDS filed February 23, 2023) as set forth previously and will not be reiterated here. Since the technical feature, i.e. a BET inhibitor, is taught by the prior art, the technical feature lacks novelty. As such, the technical feature linking inventions of Groups I and II does not constitute a special technical feature as defined by PCT RULE 13.2 as it does not define a contribution over the prior art. Accordingly, the species are not so linked by the same or corresponding special technical feature as to form a single inventive concept.
Claims 1-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election without traverse of (1) tert-butyl (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl- 6H-thieno [3,2-f][1,2,4]triazolo [4,3-a][1,4] diazepin-6-yl)acetate (JQ1) as the elected BET inhibitor compound species and Alzheimer’s disease as the elected disease from which the cell is obtained species in the reply filed on October 2, 2025 is acknowledged.
Claims 12-20 are presently under examination as they relate to the elected species:
JQ1 and Alzheimer’s disease
Priority
The present application is a 371 of PCT/US21/47229 filed on August 24, 2021, which claims benefit of priority to US Provisional Application No. 63/070,426 filed on August 26, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 23, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received on February 23, 2023. These drawings are accepted.
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 12 and 15-20 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. This is a written description rejection.
The Written Description Guidelines for examination of patent applications indicates, "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 by disclosure of relevant, identifying characteristics, i.e., structure or other physical characteristics and/or other 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 applicant was in possession of the claimed genus." (Federal register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see especially page 1106 column 3) and (see MPEP 2164).
Claims 12 and 15-20 are a method of inhibiting Cytosine-phosphate-Guanine negative (CGI-) gene misexpression in a cell, comprising administering an effective amount of a BET inhibitor to the cell. Thus, the claims encompass a method comprising administering a composition comprising a genus of compounds which function as a BET inhibitor. Thus, the claims encompass a genus of compounds which function as a BET inhibitor with no other defining structural components of the compound. BET inhibitors can be a small molecule, polypeptide, peptide, glycoprotein, peptide-mimetic, an antigen binding protein (ABP), a DNA, an RNA, RNAi, siRNA, shRNA, a peptide nuclei acid (PNA), a genetic construct for targeting gene editing, a CRSIPR/Cas9 construct, a guide nucleic acid and tracrRNA. Thus, the claims encompass a genus of molecules which function as a BET inhibitor with no other defined structural components to produce a composition useful in a method of inhibiting CGI- gene misexpression in a cell.
In a review of the instant specification, the specification does not appear to provide guidance as to what structural components are critical to the desired function (see below). The specification discloses various compounds as BET inhibitors (see page 2, line 1-page 3, line 6) but only disclose the CGI-gene expression downregulation effect of 1 compound (Example 8, Fig 12A-12B). Because there are an innumerably large number of bio-molecules/compounds within the scope of the generic claims, it would require extensive manpower to make and test each compound to determine which compound would possess the recited properties (i.e., function as a BET inhibitor) and be useful in the instantly claimed compositions.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a 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." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he 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, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, the claims are drawn to a method of inhibiting Cytosine-phosphate-Guanine negative (CGI-) gene misexpression in a cell, comprising administering an effective amount of a BET inhibitor to the cell. Thus, the claims encompass a genus of molecules which function as a BET inhibitor with no other defined structural components to produce a composition useful in a method of inhibiting CGI- gene misexpression in a cell.
The claims are generic, broadly reciting a genus of “a BET inhibitor.”
As stated supra, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claims 1, 7, and 8 are broad and generic, with respect to all possible compounds encompassed by the claims.
Applicant has failed to show that they were in possession of all the diverse compounds encompassed by a BET inhibitor. Applicant discloses a very narrow set of compounds described as a BET inhibitor, despite claiming any compound functioning as a BET inhibitor. The possible variation of any molecule that functions as a BET inhibitor within the scope of claims 12 and 15-20 are limitless and would encompass compounds that function as a BET inhibitor not yet discovered. In a review of the instant specification, the specification does not appear to provide guidance as to what structural components are critical to the desired function (see below). The specification discloses various compounds as BET inhibitors (see page 2, line 1-page 3, line 6) but only disclose the CGI-gene expression downregulation effect of 1 compound (Example 8, Fig 12A-12B). Because there are an innumerably large number of bio-molecules/compounds within the scope of the generic claims, it would require extensive manpower to make and test each compound to determine which compound would possess the recited properties (i.e., function as a BET inhibitor) and be useful in the instantly claimed compositions. The small set of compounds cannot be viewed as being reasonably representative of the genus in its claimed scope because no readily apparent combination of identifying characteristics is provided.
Given the broad scope of the claimed subject matter, Applicant has not provided sufficient written description that would allow the skilled in the art to recognize all the compounds claimed to be useful in the compositions of claims 12 and 15-20.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 12-14 and 16-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Magistri et al (Current Alzheimer Research, 2016; 13:985-995).
Regarding claim 12-14, 16, and 17, Magistri teaches Alzheimer’s disease (AD) is an age-related neurodegenerative disease characterized by progressive loss of memory and other cognitive functions (page 985, left, 1st paragraph); the triple transgenic 3xTg mouse model of Alzheimer’s disease harbors three human transgenes: the familial AD mutations APPSwe and PS1m146v and the TauP301L mutation which is found in frontotemporal dementia (page 986, left); and 20 male 3xTg mice started to receive intraperitoneal (IP) injections when they were 3 months old; half of the mice received 1 injection per day for 5 days a week of JQ1 (50mg/kg), while the other half received vehicle control solution; 12 weeks-old mice were injected for 15 weeks (Fig. 1) (page 986, right, 2nd paragraph). Magistri teaches JQ1 treatment reduced splenomegaly and neuroinflammation in the brain of treated mice where we observed a reduction in the expression of the pro-inflammatory modulators Il-1b, Il-6, Tnfa, Ccl2, Nos2 and Ptgs2; JQ1-treated mice showed a reduction of tau phosphorylation at Ser396 in the hippocampus and frontal cortex while total levels of tau remained unaffected (abstract). Administering JQ1 to a triple transgenic 3xTg mouse model of Alzheimer’s disease reads on administering an effective amount of a BET inhibitor to a cell wherein the cell is present in an age-related inflammatory disease, Alzheimer’s disease.
The prior art is silent regarding “inhibiting cytosine-phosphate-guanine negative (CGI-) gene misexpression in a cell.” However: “inhibiting CGI-gene misexpression in a cell” will inevitably flow from the teachings of the prior art (see above rejection), since the same compound (JQ1) is being administered to the same subjects (a cell present in an Alzheimer’s disease). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding “inhibiting CGI-gene misexpression in a cell,” by practicing the method made obvious by the prior art: "the administration of an effective amount of JQ1 to a cell present in Alzheimer’s disease,” one will also be “inhibiting CGI-gene misexpression in a cell,” even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage (“inhibiting CGI-gene misexpression in a cell”) of the method made obvious by the prior art (“the administration of an effective amount of JQ1 to a cell present in Alzheimer’s disease”).
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).”
With regard to claims 18-20, Magistri teaches the elected compound, JQ1, is useful to reduce neuroinflammation in mouse model of Alzheimer’s disease. In performing the active step (i.e. administering an effective amount of the JQ1 taught by Magistri to a cell from Alzheimer’s disease), the method would necessarily result in inhibition of nuclear lamina and/or heterochromatin disruption; inhibition of CGI-misexpression associated organ failure; and/or inhibition of age-associated degenerative changes.
In regard to "wherein” clauses, MPEP 2111.04 states:
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. In the instant case, the wherein clause is directed to the intended result (i.e. inhibition of nuclear lamina and/or heterochromatin disruption; inhibition of CGI-misexpression associated organ failure; and/or inhibition of age-associated degenerative changes) of the process step positively recited (i.e. administering JQ1 to an cell present in Alzheimer’s disease).
Thus, the teachings of Magistri anticipate the method of claims 12-14 and 16-20.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 15 is rejected under 35 U.S.C. 103 as being unpatentable over Magistri et al (Current Alzheimer Research, 2016; 13:985-995).
Magistri teaches all the limitations of claim 15 (see above 102), except wherein the cell is a senescent cell.
However, Magistri teaches to test whether JQ1 treatment had any beneficial effects on animal cognition we began drug treatment when 3xTg mice were 3 months old and we daily administered the drug for almost 4 months; at this point we tested animals cognition with a series of behavioral tests aimed at measuring hippocampus- and cortex- dependent learning and memory; despite the encouraging results showing reduction of neuroinflammation and tau phosphorylation, behavioral tests revealed no improvement in cognition in JQ1-treated 7-month-old mice; this could be due to the relatively young age of treated mice cohort and the late start of behavioral impairment in 3xTg mice; as reported by previous studies, 3xTg mice at this age start to develop impairments in spatial working memory; however, more severe deficits in recognition memory and reference memory only appear between 9 and 12 months of age; more experiments using JQ1 for a prolonged period of time and in different age windows should be performed to test the effects of the drug on mice cognition (page 993, left, 1st paragraph). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to administer JQ1 to a senescent 3xTg mouse, since the prior art teaches that severe deficits in recognition memory and reference memory only appear between 9 and 12 months. The skilled artisan would have been motivated to test senescent mice to determine if JQ1 would reduce reduction of neuroinflammation and tau phosphorylation and show improvement in cognition in aged mice.
Taken together, all this would result in the practice of the method of claim 15 with a reasonable expectation of success.
Conclusion
Claims 12-20 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Rayna Rodriguez/Primary Examiner, Art Unit 1628