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 .
Non-Final Rejection
The Status of Claims:
Claims 1-12 are pending.
Claims 1-12 are rejected.
Claims 1-8 and 10-12 are objected.
DETAILED ACTION
1. Claims 1-12 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/FR2022/050977 05/23/2022 ,which has a foraging priority document, FRANCE FR2105360 05/21/2021.
Drawings
3. The drawings filed on 11/21/2023 are accepted by the examiner None.
IDS
4. The IDS filed on 12/05/23 and 11/21/23 are reviewed by the examiner.
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 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.
Claim Objections
Claims 1-8 and 10-12 are objected to because of the following informalities:
In claim 1, the expression of the parenthesis “(in particular 4-fluorophenyl)” is recited. The expression can be improper. The examiner recommends to remove the parenthesis from the claim.
In claim 5, the expression of the parenthesis” (in particular fluorine or bromine)” is recited. The expression can be improper. The examiner recommends to remove the parenthesis from the claim.
Appropriate correction is required.
claims 2-8 and 10-12 are objected to for the phrase "for use according to...". This is not conventional claim language for US practice. The claims would be more concise stating "The compound of claim...." The expression for “for use “ should be removed from the claims.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-12 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 pre-AIA the applicant regards as the invention.
In claim 1, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 1 recites the broad recitation “a C1-C6 alkyl ” , “a C6-C10 aryl, ,,” and the claim also recites “ preferably a methyl, which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “a C6-C10 aryl” and the claim also recites “ preferably a phenyl”, which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “a C1-C6 alkyl, wherein1 or several hydrogen atoms is (are) optionally replaced with a fluorine atom”, and the claim also recites “preferably a trifluoromethyl”, which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “a 5-membered heteroaryl group comprising from 1 to 3 heteroatoms independently selected from N, O and S”, and the claim also recites “such as triazole, preferably 1,2,4-triazolea”, which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “a 5-10 membered heteroaryl”, and the claim also recites “such as a furan, pyrrole, imidazole, pyrazole, thiophene, pyridine, pyrimidine, benzofuran, benzodioxole, indole, benzimidazol
”, which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “a C6-C10 aryl optionally substituted with a halogen atom”, and the claim also recites “preferably a fluorophenyl (in particular 4-fluorophenyl)”, which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “optionally substituted with a halogen atom, a hydroxyl, a C1-C6 alkyl, or a C1-C6 alkoxyl”, and the claim also recites “preferably a fluorine atom, a hydroxyl, a methoxy or a trifluoromethyl, even more preferably a hydroxyl”, which is the narrower statement of the range/limitation.
In the present instance, claim 1 recites the broad recitation “ a C6-C10 aryl optionally substituted with a halogen atom and/or a C1-C6 alkyl”, and the claim also recites “ in particular a phenyl optionally substituted with a halogen atom and/or a Ci-C6 alkyl, preferably a phenyl optionally substituted with a halogen atom, in particular it is
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which is the narrower statement of the range/limitation.
In the present instance, claim 3 recites the broad recitation “Cy represents a phenyl, thiophene, furan, pyridine or pyrimidine group ”, and the claim also recites “ in particular a phenyl or a thiophene ”, which is the narrower statement of the range/limitation.
In the present instance, claim 4 recites the broad recitation “X represents a halogen,”, and the claim also recites “ in particular fluorine ”, which is the narrower statement of the range/limitation.
In the present instance, claim 5 recites the broad recitation “a halogen atom”, and the claim also recites “ (in particular fluorine or bromine)”, which is the narrower statement of the range/limitation.
In the present instance, claim 7 recites the broad recitation “C6-C10 aryl optionally substituted with a halogen atom”, and the claim also recites “ preferably a fluorophenyl, in particular 4-fluorophenyl”, which is the narrower statement of the range/limitation.
In the present instance, claim 7 recites the broad recitation “R represents a C6-C10 aryl”, and the claim also recites “ in particular a phenyl, optionally substituted with a halogen atom, in particular substituted cyclopropyl of formula
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”, which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The examiner recommends to put the narrower limitations to their corresponding dependent claims.
In claim 1 , the limitation “a 5-10 membered heteroaryl comprising from 1 to 3 heteroatoms independently selected from N, O and S, in particular a 5-membered heteroaryl group” is recited first; then another limitation” a 5-10 membered heteroaryl containing from 1 to 3 heteroatoms independently selected from N, O and S, such as a furan, pyrrole, imidazole, … benzimidazole” is recite. These expressions can be confusing because similar definitions for the 5-10 membered heteroaryl group are defined twice; the examiner recommends to put those limitations into a single form of its definition in the claim.
Regarding claims 1, 11-12, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 1-12 provide for a compound of formula (I) or its pharmaceutical composition for use in the prevention and/or treatment of viral infections, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
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 1-12 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treating specific diseases, does not reasonably provide enablement for prevention of viral infections. 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. Applicants are not enabled for preventing any of these diseases. The only established prophylactics are vaccines not the compounds of Formula(I) such as present here. In addition, it is presumed that “prevention” of the claimed diseases would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
“The factors to be considered [in making an enablement rejection] have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art, and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546. 1) As discussed above, preventing diseases requires identifying those patients who will acquire the disease before viral infections occur. This would require extensive and potentially opened ended clinical research on healthy subjects. 2)
The passages spanning line1 to line 5 on page 6 lists the diseases Applicant intend to treat. 3) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical anti-viral infection medicine and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will become the patients for viral infections before the fact. 6) The artisan using Applicants invention would be a Board Certified physician in anti-viral infections with an MD degree and several years of experience. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of viral infections generally. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent viral infections generally. That is, the skill is so low that no compound effective generally against viral infections has ever been found let alone one that can prevent such conditions. 7) It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved", and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed viral infections and on the claimed compounds.
The Examiner suggests deletion of the word “prevention”.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
5. Claims 1-4 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Engelhardt et al (WO 2010/007114 A2).
Applicants claim the followings:
1. (Original) A compound of formula (I):
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Cy(i) in which X represents a hydrogen atom or a halogen atom, Y is selected from -CH20H, -CH=NOH, -CH2NH2, an aryl optionally mono- or polysubstituted, a heteroaryl optionally mono- or polysubstituted, and -L-(CH2)p-W, - L represents -C(O)NH-, -CH2NH-, -CH=N-, -NHC(O)-, or -CH2N=CH.or a pharmaceutically acceptable salt thereof or a mixture thereof, for use in the prevention and/or treatment of viral infections.
2. (Original) The compound for use according to claim 1, of formula (la):Cy
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(la), wherein X, Y and Cy are as defined in claim 1.
3. (Previously Presented) The compound for use according to claim 1, characterized in that Cy represents a phenyl, thiophene, furan, pyridine or pyrimidine group, in particular a phenyl or a thiophene.
4. (Previously Presented) The compound for use according to claim 1, characterized in that X represents a halogen, in particular fluorine.
9.(Currently Amended) A pharmaceutical composition comprising a compound ccording to any one of claims 1 to 8 claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable excipient for use in the prevention and/or treatment of viral infections.
10. (Original) The pharmaceutical composition for use according to claim 9, further comprising an additional therapeutic agent, chosen from an antiviral agent, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, an agent for the treatment of immunodeficiency disorders and an agent for pain treatment.
11. (Previously Presented) A compound for use according to claim 1, wherein the viral infections are due to Flaviviruses, such as dengue virus, Zika virus, West Nile virus, Kunjin virus, Alphaviruses, such as Chikungunya virus, Mayaro virus, Semliki Forest virus, Sindbis virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Filoviruses such as Ebola virus, Marburg fever virus, arenaviruses such as Lassa fever virus, Junin virus, Amapari virus, picornaviruses such as vesicular stomatitis virus, paramyxoviruses such as influenza virus, or coronaviruses such as SARS-COV2.
Determination of the scope and content of the prior art
Engelhardt et al disclose the following compounds and their compositions:
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(see page 143, compounds# III-5 & III-6)
On the basis of their biological properties the compounds of general formula(1), they can be suitable for treating viral infections ( e.g. HIV and Kaposi's sarcoma); inflammatory and autoimmune diseases ( e.g. colitis, arthritis, Alzheimer's disease, glomerulonephritis and wound healing); bacterial, fungal and/or parasitic infections; leukemias, lymphomas and solid tumors (e.g. carcinomas and sarcomas), skin diseases ( e.g. psoriasis); diseases based on hyperplasia which are characterized by an increase in the number of cells ( e.g. fibroblasts, hepatocytes, bones and bone marrow cells, cartilage or smooth muscle cells or epithelial cells (e.g. endometrial hyperplasia)); bone diseases and cardiovascular diseases ( e.g. restenosis and hypertrophy). They are also suitable for protecting proliferating cells (e.g. hair, intestinal, blood and progenitor cells) from DNA damage caused by radiation, UV treatment and/or cytostatic treatment (see page 195, lines 6-15).
The current invention, however, differs from the prior art in that the portion of the L (-NHC(O)-) group of Y in the claimed compounds of formula (I) is attached directly to the phenyl group unlike the prior art compounds of formula (I).
Ascertainment of the difference between the prior art and the claims
The difference between the instant application and the applied Engelhardt et al prior art is that the Engelhardt et al does not expressly teach the portion of L (-NHC(O)-) group of Y) being attached directly to the phenyl group.
Resolving the level of ordinary skill in the pertinent art.
Regarding the Claims1-4 and 9-11 , with respect to the lack of disclosing the portion of L (-NHC(O)-) group of Y) being attached directly to the phenyl group, the prior art is silent about it. However, the prior art does disclose the following compounds:
:
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.
The relation between the prior art and the claimed invention are very similar with their corresponding chemical structures with the only difference of the presence or the absence of a CH2 group as well as their common use in the treatment of viral infections.
Furthermore, according to a case law, adjacent homologs are considered to be obvious absent unexpected results. In re Henze, 85 USPQ 261, 263 (CCPA 1950).
In addition, obviousness based on similarity of structure and function entails motivation to make the claimed compound in expectation that compounds similar in structure will have similar properties.
So, if the skilled artisan in the art had desired to develop a compound containing the portion of L (-NHC(O)-) group of Y) being attached directly to the phenyl group as an alternative for the purpose of exhibiting similar properties, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to do so in the Engelhardt et al. This is because the skilled artisan in the art would expect such a modification to be successful and feasible as guidance shown in the prior art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Engelhardt et al expressly disclose the following compounds and their compositions useful for treating viral infections:
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(see page 143, compounds# III-5 & III-6)
Although the prior art does not teach that the portion of the L (-NHC(O)-) group of Y in the compounds of formula (I) is attached directly to the phenyl group, their only chemical structural difference is the presence or the absence of a CH2 group between them.
Because of given that the high structural similarity of the compounds of the prior art with the claimed compounds of formula (I), a person skilled in the art would have expected these compounds to exhibit beneficial properties identical or at least similar to those exhibited by the compounds disclosed in the cited prior art when they are used in the treatment of viral infections.
So, if the skilled artisan in the art had desired to develop a compound containing the portion of L (-NHC(O)-) group of Y) being attached directly to the phenyl group as an alternative for the purpose of exhibiting similar properties, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to do so in the Engelhardt et al. This is because the skilled artisan in the art would expect such a modification to be successful and feasible as guidance shown in the prior art.
Conclusion
Claims 1-12 are rejected.
Claims 1-8 and 10-12 are objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached on 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached on 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 1/21/2026