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 .
Election/Restrictions
Applicant’s election without traverse of the species A is
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and the corresponding compound
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in the reply filed on 1/5/26 is acknowledged.
The search of the elected species further identified compounds comprising A is
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and
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and therefore, the search was extended to include these A moieties.
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 1-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
Claims 1-25 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.
The claimed Markush structure contains so many possible variation that the scope of the claim cannot be determined. While breadth alone is not indefinite, the instant claims have an almost unlimited number of possible combinations of chemical moieties that it is not possible to determine the metes and bounds of the claims.
The dependent claims fall therewith.
Claims 1-25 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if: (1) the species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No.
27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The claims are directed to the compounds of Formula I having many different chemical
structures comprising numerous possible alternative variation of R, R1, A, R2, R3 and R4 substituents, such
as alkyls, alkenyls, alkynyls, cycloalkyls, aryls, heterocycles, halides, radioactive atoms, amines, amides, cyano, ether, thioether, sulfonyl, sulfonamide, carboxyl, etc. wherein at least one of R, R1, A, R2, R3, R4 or R5 must be radiolabeled. There is nothing of record to show a common chemical core that is specifically tied to a function in the almost unlimited breadth of the claimed compounds.
Applicant attention is directed to the third paragraph of MPEP 803.02 which discloses: “Since the decisions in In re Weber, 580 F.2d 455, 198 USPQ 328 (CCPA 1978) and In re Haas, 580 F.2d 461, 198 USPQ 334 (CCPA 1978), it is improper for the Office to refuse to examine that which Applicants regard as their invention, unless the subject matter in a claim lacks unity of invention. In re Harnisch, 631 F.2d 716, 206 USPQ 300 (CCPA 1980); and Ex parte Hozumi, 3 USPQ2d 1059 (Bd. Pat. App. & Int. 1984). Broadly, unity of invention exists where compounds included within a Markush group (1) share a common utility, and (2) share a substantial structural feature essential to that utility.”
In the instant case, if it is asserted that the claims share a common utility, it is noted the only shared structure is the phenylsulfonyl moiety that is substituted with a plethora of different and distinct chemical moieties. In addition, the variety of substituted heterocyclic A moieties containing one or more heteroatom that is connected directly to the phenylsulfonyl moiety does not allow the genus to have an art recognized classification. Hence, the Markush grouping is improper.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to
the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1)
(emphasis provided).
The dependent claims fall therewith.
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.
Claim(s) 1 and 4-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tietz et al. (Org. Biomol. Chem., 2013, 11, 8052-8064).
Tietz et al. (Org. Biomol. Chem., 2013, 11, 8052-8064) teaches of the 18F-labelled COX-2 inhibitor radiotracer
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(Fig. 1).
The
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moiety anticipates the
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moiety of the of the instant claims when R is methyl and R1 is hydrogen.
The
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moiety anticipates the A
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moiety of the instant claims when R2 is hydrogen and R3 is CF3.
The
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moiety anticipates R4 is OR5 of the instant claims when R5 is alkyl-aryl substituted with 18F.
Claim(s) 1,3,5,9,22-25,35 and 37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated Toyokuni et al. (WO03/089013).
Toyokuni et al. (WO03/089013) teaches of the COX-2 inhibitor imaging probes
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(p15) that anticipates
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of the instant claim 37
and
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that anticipates the
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of the instant claim 35.
The
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moiety anticipates the
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moiety of the of the instant claims when R is methyl and R1 is hydrogen.
The
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moiety anticipates the
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moiety of the instant claims.
The
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moiety anticipates the R2 is phenyl optionally substituted with 18F of the instant claims.
The
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moiety anticipates the R2 is phenyl of the instant claims.
The CF3 and CF318F anticipates the R4 is CF3 and CF218F, respectively of the instant claims.
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.
Claim(s) 1,2,4,5 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Toyokuni et al. (WO03/089013).
Toyokuni et al. (WO03/089013) discloses the COX-2 inhibitor imaging probes
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(abstract; p3, lines 4+; p5, lines 25+).
The A moiety comprises a 6-membered ring selected from heteroaryl (p3, lines 10-11; p6, lines 3-4), such as pyrimidyl (p8, line 30) that encompasses the
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or
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moieties of the instant claims.
The R1 moiety comprises a methylsulfone (p3, line 12; p6, line 5) that encompasses the
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moiety of the instant claims.
The R2 moiety comprises an aryl group (p3, lines 13-14; p7, lines 6-7), such as phenyl (p10, lines 1-9) that encompasses the aryl (e.g. phenyl) of the instant claims.
The R3 moiety comprises a linear or branched alkyl that comprises a radioactive isotope (p3, lines 15-16; p7, line 8), such as a radioactive halide (p4, lines 5-6) that encompasses CH218F, (CH2)218F, CF218F, etc. of the instant claims
The radioactive halogen comprises 18F (p3, lines 26-28; p17, lines 14-25; p25, lines 7-13) that encompasses the 18F of the instant claims.
The R4 comprises hydrogen (p3, line 17; p6, line 9) that encompasses the R1 is hydrogen of the instant claims.
Toyokuni et al. does not explicitly disclose binding the methylsulfone to the positions identified
by a
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in the groups
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or
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of the instant claims.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the methylsulfone is bound to the pyrimidyl moiety at the positions identified by a
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in the groups
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or
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as the pyrimidyl of Toyokuni et al. is substituted a positions R2 and R3 and therefore, a finite number of positions remain around the pyrimidyl moiety to bind the methylsulfone moiety.
Claim(s) 1,3,5,9,22-25 and 38-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Toyokuni et al. (WO03/089013).
Toyokuni et al. (WO03/089013) discloses the COX-2 inhibitor imaging probes
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(abstract; p3, lines 4+; p5, lines 25+).
The A moiety comprises a 5-membered ring selected from heteroaryl (p3, lines 10-11; p6, lines 3-4), such isoxazolyl (p6, lines 15-16) that encompasses the
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moiety of the instant claims.
The R1 moiety comprises a methylsulfone (p3, line 12; p6, line 5) that encompasses the
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moiety of the instant claims.
The R2 moiety comprises an aryl group (p3, lines 13-14; p7, lines 6-7), such as phenyl (p10, lines 1-9) that encompasses the R2 is aryl (e.g. phenyl) of the instant claims.
The R3 moiety comprises a linear or branched alkyl that comprises a radioactive isotope (p3, lines 15-16; p7, line 8), such as a radioactive halide, CD218F, CF218F, etc. (p4, lines 5-7) that encompasses CH218F, (CH2)218F, CF218F, CD218F, etc. of the instant claims
The radioactive halogen comprises 18F (p3, lines 26-28; p17, lines 14-25; p25, lines 7-13) that encompasses the 18F of the instant claims.
The R4 comprises hydrogen (p3, line 17; p6, line 9) that encompasses the R1 is hydrogen of the instant claims.
With regards to the instant claim 25, alternatively, R4 comprises a radioactive isotope, such as 18F (p4, lines 21-22).
With regards to the instant claims 39 and 40, alternatively, R3 moiety comprises a linear or branched alkyl halide (p6, line 8) and R4 comprises a radioactive isotope, such as 18F (p4, lines 21-22).
With regards to the instant claim 38, Toyokuni et al. does not disclose R2 is a 18F substituted pyridyl moiety.
Toyokuni et al. discloses that the R2 moiety comprises a heteroaryl, such as pyridyl that encompasses the R2 is heteroaryl (e.g. pyridyl) of the instant claims. The heteroaryl can have one to three substituents, such as halo (p9, lines 1-18).
Toyokuni et al. further discloses the COX-2 inhibitor
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Formula II (p15).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the phenyl moiety of Formula III of Toyokuni et al. with a pyridyl moiety that may be substituted with a halogen, such as 18F for the advantage of examining the inhibitory properties via PET.
With regards to the instant claims 41 and 42, Toyokuni et al. does not explicitly disclose a structure wherein R3 moiety comprises CH218F or CD218F.
Toyokuni et al. further discloses the compound the COX-2 inhibitor
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Formula III (p15).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the CF318F of Formula III of Toyokuni et al. for CH218F or CD218F as the R3 moiety comprises a variety of radiolabeled alkyl substituents and it would have been predictable to examine specificity and potency of the imaging probes as Toyokuni et al. teaches that the deuterium substitution in the fluoromethyl group slows kinetics of the proton abstraction thus decreasing the rate
of metabolism and increasing the bioavailability of the imaging probes (p4, lines 13-16).
Claim(s) 1,2,5-18,28 and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cortes-Salva et al. (Molecules 2018, 23, 2850, p1-10) in view of Tietz et al. (Org. Biomol. Chem., 2013, 11, 8052-8064) and in further view of Toyokuni et al. (WO03/089013).
Cortes-Salva et al. (Molecules 2018, 23, 2850, p1-10) discloses the COX-2 inhibitor compound
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(p6, scheme 1).
The
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encompasses the
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moiety of the of the instant claims when
R is methyl and R1 is hydrogen.
The
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encompasses the
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moiety of the of the instant claims when R2 is halogen and R3 is hydrogen.
The
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encompasses the R4 is N(R5)2 moiety of the instant claims, such as
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.
Cortes-Salva et al. does not disclose the fluorine is 18F.
Cortes-Salva et al. further discloses the 18F-radiolabelled COX-2 inhibitor PET radioligands
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,
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(Scheme 2).
Tietz et al. discloses the 18F-labelled COX-2 inhibitor radiotracer
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(Fig. 1) as well as that stated above.
Tietz et al. further discloses that a non-invasive way to monitor COX-2 expression in vivo to elucidate basic pharmacology of the enzyme that plays a role in the development and progression of various diseases (p8053, left column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the fluorine of Cortes-Salva et al. for 18F as Tietz et al. teaches of the advantage of in vivo monitoring of COX-2 via PET and its role in the development and progression of various diseases and Cortes-Salva et al. envisioned 18F radiolabeling of COX-2 inhibitors for in vivo PET detection of inflammation.
With regards to claim 31, Cortes-Salva et al. does not disclose A is
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.
Toyokuni et al. (WO03/089013) discloses the COX-2 inhibitor imaging probes
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(abstract; p3, lines 4+; p5, lines 25+) as well as that stated above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the pyrimidyl moiety of Cortes-Salva et al. for the pyrimidyl moiety
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of Toyokuni et al. as the pyrimidyl of Toyokuni et al. is substituted a positions R2 and R3 and therefore, a finite number of positions remain around the pyrimidyl moiety to bind the methylsulfone moiety and also to examine the efficacy of COX-2 inhibition of the resulting imaging probe via in vivo PET.
Conclusion
Claims 26,27,29,30,32-34 and 36 are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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/MELISSA J PERREIRA/ Examiner, Art Unit 1618