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 Claims
Claims 23-31 and 43-56 are pending.
Priority
Instant application 18/323,277, filed 5/24/2023 claims priority as follows:
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Information Disclosure Statement
All references from IDS(s) received 08/24/2023 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 23-31 and 43-56, in the reply filed on 04/28/2026 is acknowledged. Applicant’s election without traverse of the grouping of species reading on the generic formula recited in either claim 23 or 43 wherein:
R1 is halogen; R4 is alkyl; and R5 is hydrogen is also acknowledged.
Examination will begin with the elected species. In accordance with MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and applicable art was not identified (though double patenting references were identified). Therefore, the scope of the search was extended to encompass a limited number of species which are anticipated by the prior art. The search was not extended unnecessarily to cover all non-elected species.
Therefore, the entire scope of claims 23-31 and 43-56 has not yet been examined in accordance with Markush search practice.
Claim Objections
Applicant is advised that should claim 53 be found allowable, claim 54 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(a)
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 23-31 and 43-56 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 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. The courts have stated that, “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 claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully 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 that, “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 lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Independent claims 23 and 43 recite genera defined by independent variables R1, R4, R5, the integer n, and (claim 43 only) X. R1 is recited as twelve functional group classes (hydrogen, hydroxy, alkoxy, halogen, haloalkoxy, alkyl ester, amine, alkylamine, dialkylamine, thio, thioalkyl, alkyl ethers); R4 and R5 are each recited as seven independently selected classes; X is selected from carbon and nitrogen; and n is unbounded.
The specification discloses approximately 11 specific compounds Formulas I-XI, FIGS. 1-11). Every disclosed species uses R1 = F or OCH3, a single chain length (n = 1), and X = C, with the sole exception of FIG. 3 (X = N). No species is disclosed in which R4 or R5 is alkyl ester or amine.
A genus claim requires disclosure of “a representative number of species” reflecting “the variation within the genus.” MPEP 2163(II)(A)(3)(ii). The disclosed species are clustered narrowly and do not reflect the structural diversity claimed. Further, the applicant’s own IC50 data (Table 1) show greater than five-fold variation across the disclosed structural analogs, evidencing unpredictability in the relevant art. Under such conditions, “adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” MPEP 2163(II)(A)(3)(ii).
Claims 23-31 and 43-56 each incorporate the limitation “n is an integer number representing a repeating unit of the compound,” without any upper limit for n. The specification discloses only a single chain length (the pentyl linker produced by the synthesis of FIG. 13). The originally filed disclosure at para. [0012] restricted the analogous variable to “n = 0 to 3”; that limitation has been removed in the present claims without corresponding supporting disclosure. It appears that the specification does not have any support for an unbounded n.
A single disclosed value does not support an unbounded numerical range. The specification provides no basis to conclude the inventors possessed compounds with n = 5, 10, 100, or higher. This deficiency independently warrants rejection of every claim that depends, directly or indirectly, on claim 23 or claim 43.
Claim 43 recites X selected from carbon and nitrogen. Only one species with X = N is disclosed (FIG. 3; Formula III). The synthetic scheme at FIG. 13 produces only X = C compounds and provides no route to X = N analogs. One species does not establish possession of the X = N sub-genus where the specification does not indicate that the inventors invented species sufficient to constitute the sub-genus. See MPEP 2163(II)(A)(3)(ii).
Claims 28-29, 45-46, and 52-54 recite that the compound “reduces inflammation to treat a disease causing inflammation” or “reduces neuroinflammation by inhibiting H1 and H2 receptors”. The specification’s described mechanisms of action are mTOR inhibition, p53 reinitiation, and BNIP3/BNIP3L inhibition. None of these mechanisms of action are histamine-receptor pharmacology. No binding affinity, IC50, Ki, or selectivity data at H1 or H2 receptors is reported. No anti-inflammatory assay is reported for any disclosed compound. No art-recognized correlation between the disclosed 1,1-bis(aryl)alkyl urea scaffold and H1/H2 antagonism is identified.
“[D]escribing a composition by its function alone typically will not suffice to sufficiently describe the composition.” See MPEP 2163(II)(A)(3)(a). A functional recitation may suffice only “when there is a well-established correlation between structure and function.” See MPEP 2163(II)(A)(3)(i)(C)(2). No such correlation is shown here. The functional limitations therefore reflect a “wish or plan” rather than a described invention.
The description requirement of the patent statue 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.”) Accordingly, in view of the foregoing, the specification fails to provide adequate written description for the aforementioned claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
In the interest of compact prosecution, please note that Applicant may overcome the rejections by:
Reinstating an upper bound on n consistent with the original disclosure (e.g., n = 0-3 per [0012]).
Narrowing R1, R4, R5, and X to the specific substituents exemplified in Formulas I-XI; or to a list of substituents for which the specification establishes a reasonable correlation between structure and function.
Cancelling the H1/H2 receptor and anti-inflammatory functional limitations.
Claim Rejections - 35 USC § 112(b)
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 28-31, 45-46, and 52-56 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.
Claims 28-29, 45-46, and 52-54 depend from independent claims 23 or 43, which are compound (product) claims, and recite “wherein the compound reduces inflammation to treat a disease causing inflammation in a patient” or “wherein the compound reduces neuroinflammation by inhibiting H1 and H2 receptors in a patient”.
The aforementioned limitations present two issues making claims 28-29, 45-46, and 52-54 indefinite.
First, the phrases “wherein the compound reduces inflammation to treat a disease causing inflammation in a patient” or “wherein the compound reduces neuroinflammation by inhibiting H1 and H2 receptors in a patient” are functional limitations that define the compound “by what it does rather than by what it is”. See MPEP 2173.05(g) (citing In re Swinehart, 439 F.2d 210, 212, 169 USPQ 226, 229 (CCPA 1971). Functional language must provide a “clear-cut indication of the scope of the subject matter embraced by the claim.” MPEP 2173.05(g) instructs examiners to evaluate functional language using three factors: (1) whether there is a clear-cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.
The recited limitations fail these three factors. By tethering the recited mechanism (“treat a disease causing inflammation” or “inhibiting H1 and H2 receptors”) to occurrence “in a patient” and to an observable clinical result (“reduces inflammation” or “reduces neuroinflammation”), the claim conflates two distinct readings: (a) the compound need only possess the intrinsic capacity to inhibit H1/H2 receptors or treat a disease causing inflammation; or (b) the compound must actually produce a measurable reduction of inflammation or neuroinflammation in patient. MPEP 2173.05(g) recognizes that functional limitations are indefinite where the claims “merely recite[s] a description of a problem to be solved or a function or result achieved by the invention” without reciting the structure or steps that accomplish that result. The “in a patient” qualifier introduces patient-specific variables (e.g. dosing, baseline disease state, individual responsiveness) for which neither the claim nor any standard supplies objective boundaries, leaving the skill artisan unable to determine when the limitation is met.
Second, MPEP 2173.05(p) provides that “[a] single claim which claims both an apparatus and the method steps of using the apparatus is indefinite,” citing In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011). The issue identified in MPEP 2173.05(p) and Katz is that for claims reciting both a product and a process of using that product, the public cannot determine “whether infringement occurs when one creates [the product], or whether infringement occurs when the user actually uses” it.
Claims 28-29, 45-46, and 52-54 are apparently directed only to “the compound” of claim 23 or 43, but the qualifier “in a patient” imports a use context. The recited reduction of (neuro)inflammation cannot occur until the compound is administered to and acts within a patient. Under one reasonable interpretation, the claim therefore covers both the compound itself and the in vivo activity that results from its administration to a patient. This causes ambiguity: does infringement occur when one makes or sells the compound, or only when one administers the compound to a patient and achieves the recited physiological effect?
Therefore, in view of the foregoing, claims 28-29, 45-46, and 52-54 are indefinite.
Claims 30-31 and 55-56 are indefinite because the preamble identifies the claims as directed to “a compound,” which under its ordinary and customary meaning refers to a single chemical substance, while the body recites that the compound “comprises an aqueous solution and one or more pharmaceutically acceptable excipients, additives, carriers, or adjuvants” or “comprises one or more excipients, carriers, additives, adjuvants, or binders in a tablet or capsule”. The latter recitations describe multi-component compositions or formulations rather than a single compound. Under the broadest reasonable interpretation standard set forth in MPEP 2173.02, a person of ordinary skill in the art is left with at least two reasonable but incompatible interpretations of the claims: (1) the claims are directed to a single compound (making the wherein clause internally contradictory because a single compound cannot itself comprise a solution and carriers); or (2) the claims are directed to pharmaceutical compositions or formulations (meaning the preamble mischaracterizes the claimed subject matter). The metes and bounds are therefore unclear.
Therefore, in view of the foregoing, claims 30-31 and 55-56 are indefinite.
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 23, 28-31, 43-46, and 49-56 are rejected under 35 U.S.C. 102(a)(1) and/or 102(a)(2) as being anticipated by DEPREZ (WO 2008006625 A2; cited in IDS).
Deprez discloses urea derivatives of Formula (I) and pharmaceutical compositions thereof (see Abstract):
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and specifically exemplifies the following urea derivatives, which is not exhaustive, that read on the Formula of instant claims 23 and 43 (see, for example, para. 18-131, and Examples 1-43):
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With respect to claims 23 and 43-44, the compounds exemplified by Deprez anticipate the formula of instant claim 1 when n = 0 and X = C.
With respect to claims 49-51, Deprez discloses the compound:
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Which reads on the formula when X is C, N is 0, R1 is a halogen (chlorine) and R5 is a trifluoromethyl radical.
With respect to claims 30-31 and 55-56, Deprez discloses pharmaceutical compositions comprising the compounds of Formula (I) and pharmaceutically inert excipients and/or additives (see para. 0328).
With respect to claims 28-29, 45-46, and 52-54, Deprez discloses that the compounds of Formula (I) have utility for treating neurodegenerative disease (page 22, last para. to page 23, end of first para.). Additionally, Deprez discloses that the compound of Formula (I) have utility for treating neurodegenerative diseases or diarrhea resulting from inflammatory disorders of the gut (page 26, second para.).
Moreover, as noted in MPEP 2112.01, “Where the claimed and prior art products are
identical or substantially identical in structure or composition, or are produced by identical or
substantially identical processes, a prima facie case of either anticipation or obviousness has
been established.” Additionally, MPEP 2112.01 notes that “A chemical composition and its
properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the
properties applicant discloses and/or claims are necessarily present.” There is no requirement
that a person of ordinary skill in the art would have recognized the inherent disclosure at the
relevant time, but only that the subject matter is in fact inherent in the prior art reference.
In the instant case, Deprez discloses compounds which fall within the formula of claim 1 which one of ordinary skill would reasonably expect are capable of the functions recited in claims 28-29, 45-46, and 52-54.
Claims 43, 47, and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chemical Abstracts STN REGISTRY Database, Record for RN 138354-51-5, “N-(4-Chlorophenyl)-N'-[2-(diphenylamino)ethyl]urea”, Entered STN 17 Jan 1992.
The below compound entered the STN Registry database before the earliest priority date of the instant application and reads on claims 43, 47, and 51 when X is N, R1 is H, n is 0, R5 is H, and R4 is halogen:
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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.
11,225,459
Claims 23-24, 28-31 43-46, and 48, and 51-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,225,459 (“the ‘459 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘459 patent recites a compound having a formula (see claim 1):
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which is Formula II instantly disclosed and encompassed by the pending claims. Additionally, claims 4-5 of the ‘459 patent recite compositions comprising the compound of claim 1 and one or more pharmaceutically acceptable excipients.
12,338,204
Claims 23-31 and 43-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 12,338,204 (“the ‘204 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘204 patent recites the compounds disclosed in instant FIGS 1-11 and encompassed by the pending claims.
19/026,202
Claim 23-31 and 43-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-10of copending Application No. 19/026,202 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘202 application recites compounds having the formula:
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Wherein the underlying support for the above compound genus disclosed in the ‘202 application includes the compounds depicted in instant FIGS 1-11.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 23-31 and 43-56 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights