DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 87 and 139-157 are pending in the instant invention. According to the Amendments to the Claims, filed February 4, 2026, claims 1-86 and 88-138 were cancelled and claims 87 and 139-157 were added.
Status of Priority
This invention is a Continuation (CON) of International Application No. PCT/US2021/035460, filed June 2, 2021, which claims priority under 35 U.S.C. § 119(e) to US Provisional Application No. 63/033,559, filed June 2, 2020.
Restrictions / Election of Species
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The inventor’s or joint inventor’s provisional election of the following, without traverse, in the reply filed on February 4, 2026, is acknowledged: a) Group VII - claims 87 and 139-157; and b) substituted pentaaza macrocyclic ring complex of Formula (I) - p. 67, Compound 4419, shown to the right below, where n = 0; M = Mn2+; X = -Cl; Y = -Cl; R1 = absent; R2 = -H; R2’ = -H; R3 = -H; R4 = -H; R5 = -H; R5’ = -H; R6 = -H; R6’ = -H; R7 = -H; R8 = -H; R9 = -H; R9’ = -H; R10 = absent; ring U = -1,2-cyclohexylene-; ring V = -1,2-cyclohexylene-; and ring W = -2,6-pyridinylene-. Claims 87, 139-147, 150 and 157 read on the elected species. Affirmation
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of this election must be made by the inventor or joint inventor in replying to this Office action.
Similarly, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
Moreover, the inventor or joint inventor should further note that the combination of the functional limitations of the elected method and the elected species, shown to the right above, was found to be free of the prior art. Thus, the examiner has expanded the forthcoming prosecution to include all claims relevant to the genus of Group VII, for a first Office action and prosecution on the merits.
Thus, a first Office action and prosecution on the merits of claims 87 and 139-157 is contained within.
Specification Objection - Disclosure
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the inventor’s or joint inventor’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility invention should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase Not Applicable should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR
DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A
COMPACT DISC.
(f) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art (including information disclosed under 37 CFR 1.97
and 1.98).
(g) BRIEF SUMMARY OF THE INVENTION.
(h) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(i) DETAILED DESCRIPTION OF THE INVENTION.
(j) CLAIM OR CLAIMS (commencing on a separate sheet).
(k) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(l) SEQUENCE LISTING (See MPEP § 2424 and 37 CFR 1.821-1.825).
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(b) above and 37 CFR 1.77(c). Revisions should particularly include and/or address: a) section headings (b-i), where applicable; and b) bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Claim Objections
Claim 87 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
A method for treating a cancer in a mammalian subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of:
(a) an anticancer therapy selected from the group consisting of a cell cycle inhibitor, a chemotherapeutic agent, a dose of ionizing radiation, a therapeutic agent that inhibits a hormone receptor pathway associated with growth of the cancer, and a therapeutic agent that inhibits a hormone receptor pathway associated with progression of the cancer; and
(b) a compound corresponding to Formula (I):
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(I)
wherein:
each ----- is independently a coordinating bond between the nitrogen heteroatom of the macrocycle and the transition metal, M;
M is Mn2+ or Mn3+;
X is halo, BF4, B(alkyl)4, B(aryl)4, CN, CN(alkyl), CN(aryl), C(O)O(alkyl), C(O)O(alkylaryl), C(O)O(aryl), C(O)S(alkyl), C(O)S(aryl), C(S)S(alkyl), C(S)S(aryl), NH3, NH(alkyl), NHC(NH)NH2, NHC(NH)NH(alkyl), NHC(NH)NH(alkylaryl), NHC(NH)NH(aryl), NHC(O)NH2, NHC(O)NH(alkyl), NHC(O)NH(alkylaryl), NHC(O)NH(aryl), NHC(S)NH2, NHC(S)NH(alkyl), NHC(S)NH(alkylaryl), NHC(S)NH(aryl), NHNH2, NHNH(alkyl), NHNH(aryl), NH(aryl), NH(heterocyclyl), NH(heteroaryl), NC-alkyl, NC-aryl, NCO, NCS, N3, NO, N+O-, NO2, NO3, H2O, OH, OBO, O(alkyl), OCN, OC(O)NH2, OC(O)alkyl, OC(O)NH(alkyl), OC(O)NH(alkylaryl), OC(O)NH(aryl), OC(O)O, OC(O)OH, OC(S)NH2, OC(S)NH(alkyl), OC(S)NH(alkylaryl), OC(S)NH(aryl), OO, OOH, OO(alkyl), OO(aryl), =O, O=O, OP(OH)2, OP(O)(OH)2, OP(O)(OH)O, OP(O)OO, OPH(O)OPH(O)O, OP(O)(OH)-OP(O)(OH)-OP(O)(OH)2, OP(S)(OH)2, OS(alkyl), OS(aryl), OS(O)alkyl, OS(O)aryl, OS(O)2O, OS(O)2OH, OS(O)(S)O, OSSO, OCl, OCl(O), OCl(O)O, OCl(O)3, OBr, OBr(O), OBr(O)O, OBr(O)3, OI(O), OI(O)3, O(phenyl), H2P(alkyl), H2P(arylalkyl), H2P(aryl), H2P(Oalkyl), H2P(Oaryl), HP(O)(Oalkyl)2, HP(O)(Oaryl)2, H2P(O)O, H2P(O)(Oalkyl), H2P(O)(Oaryl), P(O)(alkyl)3, P(O)(alkylaryl)3, P(O)(aryl)3, P(S)(alkyl)3, P(S)(alkylaryl)3, P(S)(aryl)3, SCN, SC(S)NH2, SC(S)NH(alkyl), SC(S)NH(alkylaryl), SC(S)NH(aryl), S(O)alkyl, S(O)alkylaryl, S(O)aryl, S(O)2O(alkyl), S(O)2O(aryl), SO3, HSO3, Mn(halo)4, SbF6, ascorbate, citrate, hydroxamic acid, phenylglycinate, saccharinate, salicylate, succinate, tartrate, or thiotosylate, or an anion thereof;
Y is halo, BF4, B(alkyl)4, B(aryl)4, CN, CN(alkyl), CN(aryl), C(O)O(alkyl), C(O)O(alkylaryl), C(O)O(aryl), C(O)S(alkyl), C(O)S(aryl), C(S)S(alkyl), C(S)S(aryl), NH3, NH(alkyl), NHC(NH)NH2, NHC(NH)NH(alkyl), NHC(NH)NH(alkylaryl), NHC(NH)NH(aryl), NHC(O)NH2, NHC(O)NH(alkyl), NHC(O)NH(alkylaryl), NHC(O)NH(aryl), NHC(S)NH2, NHC(S)NH(alkyl), NHC(S)NH(alkylaryl), NHC(S)NH(aryl), NHNH2, NHNH(alkyl), NHNH(aryl), NH(aryl), NH(heterocyclyl), NH(heteroaryl), NC-alkyl, NC-aryl, NCO, NCS, N3, NO, N+O-, NO2, NO3, H2O, OH, OBO, O(alkyl), OCN, OC(O)alkyl, OC(O)NH2, OC(O)NH(alkyl), OC(O)NH(alkylaryl), OC(O)NH(aryl), OC(O)O, OC(O)OH, OC(S)NH2, OC(S)NH(alkyl), OC(S)NH(alkylaryl), OC(S)NH(aryl), OO, OOH, OO(alkyl), OO(aryl), =O, O=O, OP(OH)2, OP(O)(OH)2, OP(O)(OH)O, OP(O)OO, OPH(O)OPH(O)O, OP(O)(OH)-OP(O)(OH)-OP(O)(OH)2, OP(S)(OH)2, OS(alkyl), OS(aryl), OS(O)alkyl, OS(O)aryl, OS(O)2O, OS(O)2OH, OS(O)(S)O, OSSO, OCl, OCl(O), OCl(O)O, OCl(O)3, OBr, OBr(O), OBr(O)O, OBr(O)3, OI(O), OI(O)3, O(phenyl), H2P(alkyl), H2P(arylalkyl), H2P(aryl), H2P(Oalkyl), H2P(Oaryl), HP(O)(Oalkyl)2, HP(O)(Oaryl)2, H2P(O)O, H2P(O)(Oalkyl), H2P(O)(Oaryl), P(O)(alkyl)3, P(O)(alkylaryl)3, P(O)(aryl)3, P(S)(alkyl)3, P(S)(alkylaryl)3, P(S)(aryl)3, SCN, SC(S)NH2, SC(S)NH(alkyl), SC(S)NH(alkylaryl), SC(S)NH(aryl), S(O)alkyl, S(O)alkylaryl, S(O)aryl, S(O)2O(alkyl), S(O)2O(aryl), SO3, HSO3, Mn(halo)4, SbF6, ascorbate, citrate, hydroxamic acid, phenylglycinate, saccharinate, salicylate, succinate, tartrate, or thiotosylate, or an anion thereof;
R1 is absent;
R2 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R2’ is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R3 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R4 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
ring U is a partially saturated, fully saturated, or unsaturated fused carbocyclyl;
wherein the fused carbocyclyl contains 3, 4, 5, 6, 7, 8, 9, or 10 ring carbon atoms; and
wherein ring U is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, hydrocarbyl, hydrocarbyl-OR11, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R5 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R5’ is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R6 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R6’ is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R7 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R8 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
ring V is a partially saturated, fully saturated, or unsaturated fused carbocyclyl;
wherein the fused carbocyclyl contains 3, 4, 5, 6, 7, 8, 9, or 10 ring carbon atoms; and
wherein ring V is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, hydrocarbyl, hydrocarbyl-OR11, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R9 is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R9’ is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl, wherein the hydrocarbyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
R10 is absent;
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, wherein ring W is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, hydrocarbyl, hydrocarbyl-OR11, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, and heterocyclyl;
each R11 is independently H or alkyl, wherein the alkyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)H, C(O)alkyl, C(O)NH2, C(O)NH(alkyl), C(O)N(alkyl)2, C(O)OH, C(O)O(alkyl), NH2, NH(alkyl), N(alkyl)2, NHOH, NHO(alkyl), N(alkyl)OH, N(alkyl)O(alkyl), HP(O)(OH), HP(O)(Oalkyl), P(O)(alkyl)(OH), P(O)(alkyl)(Oalkyl), P(O)(OH)2, P(O)(OH)(Oalkyl), OH, O(alkyl), OP(O)OR11OR12, SH, S(alkyl), S(aryl), S(O)H, S(O)alkyl, S(O)aryl, S(O)2H, S(O)2alkyl, S(O)2NH2, S(O)2NH(alkyl), S(O)2N(alkyl)2, S(O)2aryl, carbocyclyl, and heterocyclyl;
each R12 is independently H or alkyl, wherein the alkyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C(O)H, C(O)alkyl, C(O)NH2, C(O)NH(alkyl), C(O)N(alkyl)2, C(O)OH, C(O)O(alkyl), NH2, NH(alkyl), N(alkyl)2, NHOH, NHO(alkyl), N(alkyl)OH, N(alkyl)O(alkyl), HP(O)(OH), HP(O)(Oalkyl), P(O)(alkyl)(OH), P(O)(alkyl)(Oalkyl), P(O)(OH)2, P(O)(OH)(Oalkyl), OH, O(alkyl), OP(O)OR11OR12, SH, S(alkyl), S(aryl), S(O)H, S(O)alkyl, S(O)aryl, S(O)2H, S(O)2alkyl, S(O)2NH2, S(O)2NH(alkyl), S(O)2N(alkyl)2, S(O)2aryl, carbocyclyl, and heterocyclyl;
each Z is independently a counterion; and
n is 0, 1, 2, or 3;
wherein the mammalian subject is afflicted with the cancer, has resistance to an anti-cancer therapy, and has a tumor signature indicative of dysregulation of the MnSOD-Ac-K68/ROS/HIF2a axis; and
wherein the therapeutically effective amount of the anticancer therapy is administered to the subject in need thereof prior to, concomitantly with, or after administration of the therapeutically effective amount of the compound corresponding to Formula (I).
Appropriate correction is required. See MPEP § 2173.02.
Claim 139 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation(s):
139. The method of claim 87, wherein the cancer is selected from the group consisting of breast cancer, endometrial cancer, head and neck cancer, ovarian cancer, prostate cancer, and testicular cancer.
158. The method of claim 87, wherein the tumor is a desmoid tumor.
Appropriate correction is required. See MPEP § 2173.02.
Claim 140 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein R2, R2’, R3, R4, R5, R5’, R6, R6’, R7, R8, R9, and R9’ are independently H.
Appropriate correction is required. See MPEP § 2173.02.
Claim 141 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein
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is
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 142 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein:
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is
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or
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; and
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is
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or
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 143 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(a), 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound corresponds to Formula (II):
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(II)
wherein:
RA is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl;
RB is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl;
RC is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl; and
RD is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 144 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(a), 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound corresponds to Formula (III) or Formula (IV):
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(III) or
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(IV)
wherein:
RA is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl;
RB is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl;
RC is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl; and
RD is H, hydrocarbyl, C(O)R11, C(O)NR11R12, C(O)OR11, NR11R12, NR12OR11, P(O)OR11R12, P(O)OR11OR12, OR11, OP(O)OR11OR12, SR11, S(O)R11, S(O)2R11, S(O)2NR11R12, carbocyclyl, or heterocyclyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 145 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound corresponds to Formula (V), Formula (VI), Formula (VII), Formula (VIII), Formula (IX), Formula (X), Formula (XI), Formula (XII), Formula (XIII), Formula (XIV), Formula (XV), or Formula (XVI):
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(V),
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(VI),
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(VII),
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(VIII),
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(IX),
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(X),
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(XI),
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(XII),
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(XIII),
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(XIV),
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(XV), or
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(XVI).
Appropriate correction is required. See MPEP § 2173.02.
Claim 146 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a), 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein:
X is halo, BF4, B(alkyl)4, B(aryl)4, CN, CN(alkyl), CN(aryl), C(O)O(alkyl), C(O)O(alkylaryl), C(O)O(aryl), C(O)S(alkyl), C(O)S(aryl), C(S)S(alkyl), C(S)S(aryl), NH3, NH(alkyl), NHC(NH)NH2, NHC(NH)NH(alkyl), NHC(NH)NH(alkylaryl), NHC(NH)NH(aryl), NHC(O)NH2, NHC(O)NH(alkyl), NHC(O)NH(alkylaryl), NHC(O)NH(aryl), NHC(S)NH2, NHC(S)NH(alkyl), NHC(S)NH(alkylaryl), NHC(S)NH(aryl), NHNH2, NHNH(alkyl), NHNH(aryl), NH(aryl), NH(heterocyclyl), NH(heteroaryl), NC-alkyl, NC-aryl, NCO, NCS, N3, NO, N+O-, NO2, NO3, H2O, OH, OBO, O(alkyl), OCN, OC(O)alkyl, OC(O)NH2, OC(O)NH(alkyl), OC(O)NH(alkylaryl), OC(O)NH(aryl), OC(O)O, OC(O)OH, OC(S)NH2, OC(S)NH(alkyl), OC(S)NH(alkylaryl), OC(S)NH(aryl), OO, OOH, OO(alkyl), OO(aryl), =O, O=O, OP(OH)2, OP(O)(OH)2, OP(O)(OH)O, OP(O)OO, OPH(O)OPH(O)O, OP(O)(OH)-OP(O)(OH)-OP(O)(OH)2, OP(S)(OH)2, OS(alkyl), OS(aryl), OS(O)alkyl, OS(O)aryl, OS(O)2O, OS(O)2OH, OS(O)(S)O, OSSO, OCl, OCl(O), OCl(O)O, OCl(O)3, OBr, OBr(O), OBr(O)O, OBr(O)3, OI(O), OI(O)3, O(phenyl), H2P(alkyl), H2P(arylalkyl), H2P(aryl), H2P(Oalkyl), H2P(Oaryl), HP(O)(Oalkyl)2, HP(O)(Oaryl)2, H2P(O)O, H2P(O)(Oalkyl), H2P(O)(Oaryl), P(O)(alkyl)3, P(O)(alkylaryl)3, P(O)(aryl)3, P(S)(alkyl)3, P(S)(alkylaryl)3, P(S)(aryl)3, SCN, SC(S)NH2, SC(S)NH(alkyl), SC(S)NH(alkylaryl), SC(S)NH(aryl), S(O)alkyl, S(O)alkylaryl, S(O)aryl, S(O)2O(alkyl), S(O)2O(aryl), SO3, HSO3, Mn(halo)4, SbF6, ascorbate, citrate, hydroxamic acid, phenylglycinate, saccharinate, salicylate, succinate, tartrate, or thiotosylate, or an anion thereof; and
Y is halo, BF4, B(alkyl)4, B(aryl)4, CN, CN(alkyl), CN(aryl), C(O)O(alkyl), C(O)O(alkylaryl), C(O)O(aryl), C(O)S(alkyl), C(O)S(aryl), C(S)S(alkyl), C(S)S(aryl), NH3, NH(alkyl), NHC(NH)NH2, NHC(NH)NH(alkyl), NHC(NH)NH(alkylaryl), NHC(NH)NH(aryl), NHC(O)NH2, NHC(O)NH(alkyl), NHC(O)NH(alkylaryl), NHC(O)NH(aryl), NHC(S)NH2, NHC(S)NH(alkyl), NHC(S)NH(alkylaryl), NHC(S)NH(aryl), NHNH2, NHNH(alkyl), NHNH(aryl), NH(aryl), NH(heterocyclyl), NH(heteroaryl), NC-alkyl, NC-aryl, NCO, NCS, N3, NO, N+O-, NO2, NO3, H2O, OH, OBO, O(alkyl), OCN, OC(O)alkyl, OC(O)NH2, OC(O)NH(alkyl), OC(O)NH(alkylaryl), OC(O)NH(aryl), OC(O)O, OC(O)OH, OC(S)NH2, OC(S)NH(alkyl), OC(S)NH(alkylaryl), OC(S)NH(aryl), OO, OOH, OO(alkyl), OO(aryl), =O, O=O, OP(OH)2, OP(O)(OH)2, OP(O)(OH)O, OP(O)OO, OPH(O)OPH(O)O, OP(O)(OH)-OP(O)(OH)-OP(O)(OH)2, OP(S)(OH)2, OS(alkyl), OS(aryl), OS(O)alkyl, OS(O)aryl, OS(O)2O, OS(O)2OH, OS(O)(S)O, OSSO, OCl, OCl(O), OCl(O)O, OCl(O)3, OBr, OBr(O), OBr(O)O, OBr(O)3, OI(O), OI(O)3, O(phenyl), H2P(alkyl), H2P(arylalkyl), H2P(aryl), H2P(Oalkyl), H2P(Oaryl), HP(O)(Oalkyl)2, HP(O)(Oaryl)2, H2P(O)O, H2P(O)(Oalkyl), H2P(O)(Oaryl), P(O)(alkyl)3, P(O)(alkylaryl)3, P(O)(aryl)3, P(S)(alkyl)3, P(S)(alkylaryl)3, P(S)(aryl)3, SCN, SC(S)NH2, SC(S)NH(alkyl), SC(S)NH(alkylaryl), SC(S)NH(aryl), S(O)alkyl, S(O)alkylaryl, S(O)aryl, S(O)2O(alkyl), S(O)2O(aryl), SO3, HSO3, Mn(halo)4, SbF6, ascorbate, citrate, hydroxamic acid, phenylglycinate, saccharinate, salicylate, succinate, tartrate, or thiotosylate, or an anion thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 147 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein:
X is F, Cl, Br, or I; and
Y is F, Cl, Br, or I.
Appropriate correction is required. See MPEP § 2173.02.
Claim 148 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein:
X is C(O)O(alkyl), C(O)O(alkylaryl), or C(O)O(aryl); and
Y is C(O)O(alkyl), C(O)O(alkylaryl), or C(O)O(aryl).
Appropriate correction is required. See MPEP § 2173.02.
Claim 150 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound is:
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(4419).
Appropriate correction is required. See MPEP § 2173.02.
Claim 151 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound is:
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(4403).
Appropriate correction is required. See MPEP § 2173.02.
Claim 152 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound is:
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(4401).
Appropriate correction is required. See MPEP § 2173.02.
Claim 153 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound is:
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(4498).
Appropriate correction is required. See MPEP § 2173.02.
Claim 154 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound is:
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GC4444.
Appropriate correction is required. See MPEP § 2173.02.
Claim 155 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound is:
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GC4702.
Appropriate correction is required. See MPEP § 2173.02.
Claim 156 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the compound is:
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GC4711.
Appropriate correction is required. See MPEP § 2173.02.
Claim 157 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 87, wherein the cancer and/or tumor is breast cancer or prostate cancer.
Appropriate correction is required. See MPEP § 2173.02.
Claim Rejections - 35 U.S.C. § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. § 112:
(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.
Method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I)
Claims 87 and 139-157 are rejected under 35 U.S.C. § 112(a) because the specification, while being enabling for performing a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are as presented herein in the section above entitled Claim Objections, respectively, does not reasonably provide enablement for performing a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use (perform) the invention commensurate in scope with these claims. A method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively, as recited in claim 87, has not been adequately enabled in the specification to allow any person having ordinary skill in the art, at the time this invention was made, to make and/or use (perform) a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the instant invention, are summarized as follows:
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(a) Breadth of the claims - the breadth of the claims includes a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), shown to the right, respectively;
(b) Nature of the invention - the nature of the invention is evaluation of performance of a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), shown to the right above, respectively;
(c) State of the prior art - Nature Reviews: Drug Discovery offers a snapshot of the state of the drug development art. Herein, drug development is stated to follow the widely accepted Ehrlich model which includes: (1) development of a broad synthetic organic chemistry program; (2) subsequent testing of compounds in an appropriate laboratory model for the disease to be treated; and (3) screening of compounds with low toxicity in prospective clinical trials (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205). Similarly, no single drug has been discovered that is effective in treating the myriad of cancers and/or tumors, including, but not limited to, breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer {See In re Hokum, 226 USPQ 353 (ComrPats 1985)}. Moreover, Free Radical Biology & Medicine teaches a substituted pentaaza macrocyclic ring complex of the Formula (I) which is administered within the instantly recited method of treating cancer in a mammalian subject {El-Mahdy, et al. Free Radical Biology & Medicine, 160, 2020, 630-642};
(d) Level of one of ordinary skill in the art - the artisans performing the inventor’s or joint inventor’s method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively, would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience;
(e) Level of predictability in the art - Synthetic organic chemistry is quite unpredictable (See In re Marzocchi and Horton 169 USPQ at 367 ¶3). Similarly, it is well established that [T]he 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)}. Likewise, it is unclear based on the combination of the instant specification, and El-Mahdy, et al. in Free Radical Biology & Medicine, whether the instantly recited substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject, wherein the substituted pentaaza macrocyclic ring complexes of the Formula (I) are not as presented herein in the section above entitled Claim Objections, are enabled. Next, the following excerpt is taken from Dörwald, which has relevance to the synthesis of substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject, wherein the substituted pentaaza macrocyclic ring complexes of the Formula (I) are not as presented herein in the section above entitled Claim Objections (Dörwald, F. Zaragoza. Side Reactions in Organic Synthesis: A Guide to Successful Synthesis Design, Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA, 2005, Preface):
Most non-chemists would probably be horrified if they were to learn how many attempted syntheses fail, and how inefficient research chemists are. The ratio of successful to unsuccessful chemical experiments in a normal research laboratory is far below unity, and synthetic research chemists, in the same way as most scientists, spend most of their time working out what went wrong, and why.
Despite the many pitfalls lurking in organic synthesis, most organic chemistry textbooks and research articles do give the impression that organic reactions just proceed smoothly and that the total synthesis of complex natural products, for instance, is maybe a labor-intensive but otherwise undemanding task. In fact, most syntheses of structurally complex natural products are the result of several years of hard work by a team of chemists, with almost every step requiring careful optimization. The final synthesis usually looks quite different from that originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who has experienced for himself the many failures and frustrations which the development (sometimes even the repetition) of a synthesis usually implies will be able to appraise such work.
Chemists tend not to publish negative results, because these are, as opposed to positive results, never definite (and far too copious).
Moreover, the following excerpt is taken from Hackam, et al., with respect to the poor replication of animal research in human clinical trials {Hackam, et al. JAMA, 296(14), 2006, 1731-1732}:
Only about a third of highly cited animal research translated at the level of human randomized trials. This rate of translation is lower than the recently estimated 44% replication rate for highly cited human studies. Nevertheless, we believe these findings have important implications. First, patients and physicians should remain cautious about extrapolating the findings of prominent animal research to the care of human disease. Second, major opportunities for improving study design and methodological quality are available for preclinical research. Finally, poor replication of even high-quality animal studies should be expected by those who conduct clinical research.
(f) Amount of direction provided by the inventor - the invention lacks direction with respect to making and/or using (performing) a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively;
(g) Existence of working examples - the inventor or joint inventor has provided sufficient guidance to make and/or use (perform) a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are as presented herein in the section above entitled Claim Objections, respectively; however, the disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively. The specification lacks working examples of performing a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively.
Within the specification, [A]t least one specific operative embodiment or example of the invention must be set forth. The example(s) and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP § 608.01(p) and MPEP § 2173.05.
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(h) Quantity of experimentation needed to make and/or use (perform) the invention based on the content of the disclosure - predicting whether a recited compound is in fact one that produces a desired physiological effect at a therapeutic concentration and with useful kinetics, is filled with experimental uncertainty, and without proper guidance, would involve a substantial amount of experimentation (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205-213). Furthermore, it is unclear, based on the guidance provided by the specification, whether a substituted pentaaza macrocyclic ring complex of the Formula (I), such as shown to the left, possesses utility as a therapeutic agent, useful in a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I). Thus, one of ordinary skill in the art, at the time this invention was made, would have an unreasonable expectation of success and undue experimentation in transferring the in vitro and/or in vivo method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively, to any mammalian population.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. {See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. (See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404). These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for making and/or using (performing) a method of treating cancer in a mammalian subject… the method comprising administering… (a) an anticancer therapy and (b) a substituted pentaaza macrocyclic ring complex of the Formula (I), wherein (i) the cancer or tumor is not selected from the group consisting of breast cancer, a desmoid tumor, endometrial cancer, glioblastoma, glioma, head and neck cancer, hepatocellular carcinoma, melanoma, ovarian cancer, pancreatic carcinoma, prostate cancer, renal cell carcinoma. and testicular cancer; and (ii) the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject are not as presented herein in the section above entitled Claim Objections, respectively, is clearly justified.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim Rejections - 35 U.S.C. § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. § 112:
(b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention.
Claims 87 and 139-157 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that a broad limitation together with a narrow limitation that falls within the broad limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c), MPEP § 2173.05(h), and/or Eli Lilly & Co. v. Teva Parenteral Meds., 845 F.3d 1357, 1371, 121 USPQ2d 1277, 1287 (Fed. Cir. 2017).
Similarly, the inventor or joint inventor should further note that claim 87 recites the broad limitation, or, with regard to the method of treating cancer in a mammalian subject, and the claim also independently recites and, with regard to the method of treating cancer in a mammalian subject, which is the narrower statement of the limitation.
Likewise, the inventor or joint inventor should further note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), pertaining to where broad language is followed by such as and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and consequently, not required, or (b) a required feature of the claim.
Next, the inventor or joint inventor should further note the explanation given by the Board of Patent Appeals and Interferences in the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claims 87, 139-144, 146-149 and 157 are further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the term, substituted, in claims 87, 143 and 144, with regard to RA, RB, RC, RD, R1, R2, R2’, R3, R4, R5, R5’, R6, R6’, R7, R8, R9, R9’, R10, U, V, and/or W, respectively, is a relative term which renders the claims indefinite. The term, substituted, is not defined by the claims, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification, on page 27, uses open language, such as includes, to define the term, substituted, using a boiler plate list of functional groups, such as C1-4 alkyl, etc.; however, neither the specification, nor the claims, explicitly limit the invention to any specifically disclosed or recited embodiments. Consequently, the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject have been rendered indefinite by the use of the term, substituted, with regard to RA, RB, RC, RD, R1, R2, R2’, R3, R4, R5, R5’, R6, R6’, R7, R8, R9, R9’, R10, U, V, and/or W, respectively.
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claims 87, 139, 141-144, 146-149 and 157 are further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the phrase, an amino acid side chain moiety, in claims 87, 143 and 144, with regard to RA, RB, RC, RD, R1, R2, R2’, R3, R4, R5, R5’, R6, R6’, R7, R8, R9, R9’, and/or R10, respectively, is a relative phrase which renders the claims indefinite. The phrase, an amino acid side chain moiety, is not defined by the claims, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the phrase, an amino acid side chain moiety. Similarly, the meaning of a phrase cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claims, explicitly limit the invention to any specifically disclosed or recited embodiments. Consequently, the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject have been rendered indefinite by the use of the phrase, an amino acid side chain moiety, with regard to RA, RB, RC, RD, R1, R2, R2’, R3, R4, R5, R5’, R6, R6’, R7, R8, R9, R9’, and/or R10, respectively. {See Datamize LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1347-48, 75 USPQ2d 1801, 1807 (Fed. Cir. 2005); and MPEP § 2173.05(b)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 143 is further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof, with regard to X and Y, respectively, is a relative phrase which renders the claim indefinite. The phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof. Similarly, the meaning of a phrase cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject have been rendered indefinite by the use of the phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof, with regard to X and Y, respectively. {See Datamize LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1347-48, 75 USPQ2d 1801, 1807 (Fed. Cir. 2005); and MPEP § 2173.05(b)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 144 is further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof, with regard to X and Y, respectively, is a relative phrase which renders the claim indefinite. The phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof. Similarly, the meaning of a phrase cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject have been rendered indefinite by the use of the phrase, suitable ligands which are derived from any monodentate or polydentate coordinating ligand or ligand system or the corresponding anion thereof, with regard to X and Y, respectively. {See Datamize LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1347-48, 75 USPQ2d 1801, 1807 (Fed. Cir. 2005); and MPEP § 2173.05(b)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 146 is further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that claim 146 recites the limitations, (1) amino acid and anions of ion exchange resins, with regard to X and Y; and (2) charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand, a ligand system and the corresponding anion thereof, and X and Y are independently attached to one or more of R1, R2, R2’, R3, R4, R5, R5’, R6, R6’, R7, R8, R9, R9’, and R10, with regard to X and Y, respectively, where the limitations are implausible, resulting in an incomplete valence. Claims are unduly speculative where they define only a portion of a substituted pentaaza macrocyclic ring complex of the Formula (I) administered within the method of treating cancer in a mammalian subject. Consequently, since incomplete valences are not permitted in the structure of the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject, an essential portion of the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject is indefinite and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject. {See Ex parte Pedlow and Miner, 90 USPQ 395 (Bd. Pat. App. & Int. 1951)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 149 is further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the phrase, amino acid, with regard to X and Y, respectively, is a relative phrase which renders the claim indefinite. The phrase, amino acid, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the phrase, amino acid. Similarly, the meaning of a phrase cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted pentaaza macrocyclic ring complexes of the Formula (I) administered within the method of treating cancer in a mammalian subject have been rendered indefinite by the use of the phrase, amino acid, with regard to X and Y, respectively. {See Datamize LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1347-48, 75 USPQ2d 1801, 1807 (Fed. Cir. 2005); and MPEP § 2173.05(b)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The examiner is also available on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
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/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624