DETAILED ACTION
All rejections and objections not mentioned below have been withdrawn.
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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
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The disclosure of the prior-filed application, Application No. EP21194819.5, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. A claim by claim analysis indicated a lack of support in application No. EP21194819.5 for the R1 variables including cycloalkyl, R2 variables including -OH and severally of the compounds of claim 7 including:
Thus all claims were given a priority date of 09/01/2022.
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 11-12 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention. The specification does not provide sufficient information that all mammals having a P2X7 receptor mediated condition or disease or treatment of conditions or diseases selected from neurodegenerative, cognitive, psychiatric disorders, neuropathic pain, chronic pain, inflammatory processes of the musculoskeletal muscular-skeletal system, liver fibrosis, gastrointestinal tract disorders, genitourinary genito-urinary tract disorders, ophthalmic diseases, Chronic Obstructive Pulmonary Disease (COPD), cancer, and proliferative diseases in a mammal in need thereof are treatable with pharmaceutical composition comprising compound of Formula I described in the method claims.
The instant specification fails to provide information that would allow the skilled artisan to practice the instant invention without undue experimentation. Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
(1). The Nature of the Invention:
AII of the rejected claims are drawn to an invention which pertains to a method of treatment or prevention of a disease by administering a pharmaceutical composition comprising compound of Formula I. The nature of the invention is complex in that it encompasses the treatment of all diseases having a P2X7 receptor mediated condition or disease or treatment of conditions or diseases selected from neurodegenerative, cognitive, psychiatric disorders, neuropathic pain, chronic pain, inflammatory processes of the musculoskeletal muscular-skeletal system, liver fibrosis, gastrointestinal tract disorders, genitourinary genito-urinary tract disorders, ophthalmic diseases, Chronic Obstructive Pulmonary Disease (COPD), cancer, and proliferative diseases in a mammal in need thereof .
(2). Breadth of the Claims:
The claims are very broad. The claims would reasonably encompass any disease mediated by P2X7 receptor which could be the treatment of unknown diseases in a mammal by administering a pharmaceutical composition comprising compound of Formula I. The coverage of diseases in the claim is immense. The breadth of the claims includes hundreds of diseases such as neurodegenerative, cognitive, psychiatric disorders, neuropathic pain, chronic pain, inflammatory processes of the musculoskeletal muscular-skeletal system, liver fibrosis, gastrointestinal tract disorders, genitourinary genito-urinary tract disorders, ophthalmic diseases, Chronic Obstructive Pulmonary Disease (COPD), cancer, and proliferative diseases, etc.
(3). Guidance of the Specification /(4). Working Examples::
The guidance given by the specification as to how one would administer the claimed compounds to a subject in order to treat any disease is not provided. All the examples tested (examples 1-71) do not cover even the majority of the full scope of the instant formula (I), for example wherein R1=cycloalkyl. As can be seen in the examples provided small changes in structure have a significant effect on activity. Thus there is no reasonable expectation that the full scope of the generic formula I will enable claims 11-12. See pages 64-91 of the specification.
There are no working examples for the treatment of a disease using pharmaceutical compositions comprising compounds of Formula (I) with R1 = C3-C6 cycloalkyl and there is no reliable correlation that these compounds would enable the same biological activity as the tested compounds (pages 64-91).
(5). State of the Art:
While the state of the art is relatively high with regard to treating specific disease, the state of the art with regard to treating all diseases having a P2X7 receptor mediated condition or disease or treatment of conditions or diseases selected from neurodegenerative, cognitive, psychiatric disorders, neuropathic pain, chronic pain, inflammatory processes of the musculoskeletal muscular-skeletal system, liver fibrosis, gastrointestinal tract disorders, genitourinary genito-urinary tract disorders, ophthalmic diseases, Chronic Obstructive Pulmonary Disease (COPD), cancer, and proliferative diseases generally is underdeveloped. In particular, there is no known compound which is effective against all diseases mediated by P2X7. For example, there are compounds that treat a range of diseases, but no one has ever been able to figure out how to get a compound to be effective against any disease generally. Thus, the existence of such a ''silver bullet'' is contrary to our present understanding in pharmaceutical art. This is true in part because diseases arise from a wide variety of sources, such as viruses (e.g. EBV, HHV-8, and HTLV-I), exposure to chemicals such as tobacco tars, genetic disorders, ionizing radiation, and a wide variety of failures of the body's cell growth regulatory mechanisms. For example given that the various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol. It is known (see Jin et al., Nature Reviews Drug Discovery | Volume 22 | March 2023 | 213–234) in the current art that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, to maximize efficacy and minimize toxicity. Thus, given that applicant has failed to demonstrate treatment of various cancers utilizing various compounds encompassed by formula (I) and in light of the challenge in treating various types of cancers, the examiner maintains that applicant has not enabled the claims.
(6) The predictability or unpredictability of the art:
The invention is directed to treatment of all diseases having a P2X7 receptor mediated condition or disease or treatment or prevention of conditions or diseases selected from neurodegenerative, cognitive, psychiatric disorders, neuropathic pain, chronic pain, inflammatory processes of the musculoskeletal muscular-skeletal system, liver fibrosis, gastrointestinal tract disorders, genitourinary genito-urinary tract disorders, ophthalmic diseases, Chronic Obstructive Pulmonary Disease (COPD), cancer, and proliferative diseases. It is well established that the scope of enablement various inversely with the degree of predictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839 (1970).
In the instant case the unpredictability of the art is very high because there are thousands of diseases which have fundamentally different mechanism and different causes. The method of diagnosing or treating one disease or condition does not necessitate the treatment or diagnosis of another disease or condition since diseases and conditions have unique chemical pathways by which they are expressed. Additionally, a single disease or condition can be diagnosed via multiple biochemical pathways and treated via multiple biochemical pathways. Thus, the treatment and diagnosis of diseases and conditions is highly unpredictable.
(7). The Quantity of Experimentation Necessary:
In order to practice the claimed invention, one of skill in the art would have to first envision a combination of a compound of Formula I with an appropriate pharmaceutical carrier, a dosage for each, the duration of treatment, route of treatment, etc. and, in the case of human treatment, an appropriate animal model system for one of the claimed compounds. One would then need to test the combination in the model system to determine whether or not the combination is effective for treating or preventing the claimed disease or condition. If unsuccessful, one of skill in the art would have to then need to envision a modification of the combination of the compound with an appropriate pharmaceutical carrier, compound dosage, duration of treatment, route of administration, etc. and appropriate animal model system, or envision an entirely new combination of the above and test the system again. In order to practice Applicant's invention, it would be necessary for one to conduct the preceding experimentation for each type of disease because there is no known drug effective for treating all types of diseases. Therefore, it would require undue, unpredictable experimentation to practice the claimed invention to treat or prevent the claimed diseases or conditions in a mammal by administration of a pharmaceutical composition of Formula I.
(8) The quantity of experimentation necessary:
Since every disease and disorder has its unique chemical pathway of expression, diagnosis and treatment of individual diseases and condition cannot be predicted a priori but must be determined from case to case by painstaking experimental study and when the above factors are weighed together, one of ordinary skill in the art would be burdened with undue ''painstaking experimentation study'' to determine which compounds of Formula I treats which diseases/conditions. For example, chemical modification of biomolecules may alter the biological property that is important in the use of that particular, and also other properties such as solubilities in aqueous media, binding affinities etc. Thus variety of compounds encompassed by formula (I) will have different biological properties. Considering variety of compounds covered by Formula I and the multitude of different diseases to be treated, this is a very large degree of experimentation.
Genetech, 108 F.3d at 1366 states that “a patent is not a hunting Iicense. It is not a reward for search, but compensation for its successful conclusion'' and ''[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.''
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over PEVARELLO (PEVARELLO et al., EP3398941A1, 2018-11-07) .
The reference PEVARELLO teaches the following led compound (page 40, example 55), wherein n=1, R2=aromatic phenyl substituted with halogens, R=aromatic phenyl substituted with a halogen and “The compounds of the invention can be used in treatment of conditions or diseases mediated by P2X7 receptor”(abstract).
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The reference PEVARELLO teaches also teaches the following generic formula (page 3):
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This helps to teach claims 1-7.
The reference PEVARELLO does not specifically teach a compound of claims 1-7 but instead requires picking and choosing of specific groups from a generic formula.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified PEVARELLO to get a compound of claims 1-7 because the led compound example 55 of PEVARELLO is only one change away from the compounds of the instant claims and that one change is suggested in the reference generic formula (I) which specifically suggests X=NC1-C4 alkyl. One would have a reasonable expectation of success because the change is suggested and it is only one change from a suggested compound. One would be motivated to do so because all compounds of PEVARELLO are suggested for treating conditions or diseases mediated by P2X7 receptor.
The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989).
However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Allowable Subject Matter
Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Response to Arguments
Applicant's arguments filed 07/15/2026 have been fully considered but they are not persuasive.
Claims 1-2 have been added to the 103 rejection due to the new amendment of R1= C1-4 alkyl.
The applicant’s argument that the claims are fully enabled now that claim 1 has been amended to include the experimental examples provided within the specification, or evidence that compounds of Formula I have P2X7 activity and thus can treat P2X7 diseases is not persuasive because this still does not solve the issues of : instant formula I includes a huge range of structurally different compounds that have unknown activity, the huge quantity of experiments necessary to treat all the claimed diseases, that different diseases have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol, or that treating a pathway would include treating undiscovered diseases. The argument against all diseases was a typo and was meant to read all diseases mediated by P2X7 as discussed here and mentioned in several places within the 112a rejection. While a working example is not required for every embodiment the applicant must provide “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” as the courts have made a distinction between mechanical elements, which function the same in different circumstances, yielding predictable results, and chemical and biological compounds, which often react unpredictably under different circumstances. Nationwide Chem. Corp. v. Wright, 458 F. supp. 828, 839, 192 USPQ 95, 105(M.D. Fla. 1976); Aff’d 584 F.2d 714, 200 USPQ 257 (5th Cir. 1978); In re Fischer, 427 F.2d 833, 839, 166 USPQ 10, 24(CCPA 1970). Thus, the physiological activity of a chemical or biological compound is considered to be an unpredictable art. All the examples tested (examples 1-71) do not cover even the majority of the full scope of the instant formula (I), for example wherein R1=cycloalkyl. As can be seen in the examples provided small changes in structure have a significant effect on activity. Thus there is no reasonable expectation that the full scope of the generic formula I will enable claims 11-12. Genetech, 108 F.3d at 1366 states that “a patent is not a hunting Iicense. It is not a reward for search, but compensation for its successful conclusion'' and ''[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.''
The applicants argument that carrier, dosages, treatments and durations and routes of administration are all routine experimentation is not persuasive because new patents are awarded for new methods of administration with unexpected results due to methods of administration. In addition methods of administration dependent on the drug, disease and person.
The applicants argument that a different patent was allowed with a similar disease scope is not persuasive as each patent’s allowability is considered under its own merits.
The applicant’s argument that the reference PEVARELLO doesn’t provide a reasoned basis to replace O in the example 55 with N(C1-4alkyl) because there is no motivation to select both the lead compound and the specific modification is not persuasive because any of the examples given by the reference would be considered to have the P2X7 activity and it would have been obvious that small modifications such as changing one variable suggested by the general formula would be considered to have similar enough structure to also have similar activity by one of ordinary skill in the art. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Conclusion
Claims 1-7 and 11-12 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR HASTINGS whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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