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 1, 4, 6, 8, 15, 17, 18, 25, 29, 31, 54, 55, 60, 61, 63, 64 and 68 are pending in the instant invention. According to the Amendments to the Claims, filed April 3, 2026, claims 1, 18, 29, 54 and 55 were amended and claims 2, 3, 5, 7, 9-14, 16, 19-24, 26-28, 30, 32-53, 56-59, 62 and 65-67 were cancelled.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/US2022/011560, filed January 7, 2022, which claims priority under 35 U.S.C. § 119(e) to US Provisional Application No. 63/135,427, filed January 8, 2021.
Although the inventor’s or joint inventor’s claim for the benefit of a prior-filed invention under 35 U.S.C. § 119(e) is acknowledged, the inventor or joint inventor has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. § 119(e) as follows:
The later-filed invention must be an invention for a patent, for an invention which is also disclosed in the prior-filed invention (the provisional invention). The disclosure of the invention in the prior-filed invention and in the later-filed invention must be sufficient to comply with the requirements of 35 U.S.C. § 112(a). {See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)}.
The specification of the prior-filed invention, US Provisional Application No. 63/135,427, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. § 112(a) for one or more claims of this invention for the following reason: the specification in the instant invention has been amended with respect to the scope of Formula (A-2), which now discloses amended definitions for at least L3, R30, R30 and L3, R1D, R1E, R1F, and/or AA, respectively, and is no longer coextensive with that of US Provisional Application No. 63/135,427.
Consequently, since the specification of US Provisional Application No. 63/135,427 lacks adequate support or enablement for one or more claims of the elected invention of Group I, as defined below in Restrictions / Election of Species, and in the manner provided by 35 U.S.C. § 112(a), the first Office action on the merits of all relevant claims drawn to Group I will be prosecuted according to the earliest effective filing date afforded this invention, which is that of International Application No. PCT/US2022/011560, filed January 7, 2022.
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 April 3, 2026, is acknowledged: a) Group I - claims 1, 4, 6, 8, 15, 17, 18, 25, 29, 31, 54, 55, 60 and 61; and b) substituted transcription modulator molecule of Formula (A-2) - p. 95, compound 115, shown to the right below, and hereafter referred to as N-(5-((3-((2-((1-((2R,6S)-4-(2-(4-(1-(3-methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-piperidin-4-yl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-1,28-dioxo-3,6,9,12,15,18,21,24-octaoxa-27-azatriacontan-30-yl)carbamoyl)-1-methyl-1H-imidazol-4-yl)amino)-3-oxopropyl)-carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-(3-(1-methyl-4-(1-methyl-1H-imidazole-2-carboxamido)-1H-pyrrole-2-carboxamido)propanamido)-1H-imidazole-2-carboxamide, where m1 = 2; n1 = 0; W1 = -H; Y1 = N; Z1 = NR1D, wherein R1D = -CH3; Y2 = CH;
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Z2 = NR1D, wherein R1D = -CH3; R30 = -H; L3 = -(CH2)2-; Y3 = N; Z3 = NR1D, wherein R1D = -CH3; and W2 = -.C(O)NR1ER1F, wherein R1E = -H and R1F = -optionally substituted C1-C20 heteroalkyl. Claims 1, 4, 6, 8, 15, 17, 18, 25, 29, 54, 55, 60 and 61 read on the elected species. Affirmation 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.
Likewise, the inventor or joint inventor should further note that 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 I, for a first Office action and prosecution on the merits.
Moreover, the inventor or joint inventor should further note that claims 63, 64 and 68 were withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to a nonelected or cancelled invention, there being no allowable generic or linking claim.
Thus, a first Office action and prosecution on the merits of claims 1, 4, 6, 8, 15, 17, 18, 25, 29, 31, 54, 55, 60 and 61 is contained within.
Specification Objection - Disclosure
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(c). Revisions should particularly address bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Specification Objection - Title
The inventor or joint inventor is reminded of the proper content of the title of the invention.
The title of the invention should be brief, but technically accurate and descriptive and should contain fewer than 500 characters. See 37 CFR 1.72(a) and MPEP § 606.
The title of the invention is not technically accurate and descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. In the revised title, the examiner suggests additionally identifying the substituted transcription modulator molecules of the Formula (A-2).
The following title is suggested: SUBSTITUTED TRANSCRIPTION MODULATOR MOLECULES FOR TREATING FRIEDREICH’S ATAXIA.
Appropriate correction is required.
Specification Objection - Abstract
The inventor or joint inventor is reminded of the proper content of an abstract of the disclosure.
With regard particularly to chemical patents, for compounds or compositions, the general nature of the compound or composition should be given as well as the use thereof, e.g., The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics. Exemplification of a species could be illustrative of members of the class. For processes, the reactions, reagents and process conditions should be stated, generally illustrated by a single example, unless variations are necessary. See MPEP § 608.01(b), Section B.
The abstract of the disclosure is objected to because it fails to exemplify any members or formulae illustrative of its class. Correction is required. See MPEP § 608.01(b).
The examiner suggests incorporating the structure of Formula (A-2) into the abstract, to overcome this objection.
Claim Objections
Claim 1 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 transcription modulator molecule having the following:
(a) a first terminus comprising a compound of Formula (A-2):
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Formula (A-2)
or a pharmaceutically acceptable salt thereof,
wherein:
W1 is H, C1-C6 alkyl, C(O)NR1ER1F, NR1EC(O)NR1ER1F, or (AA)1-10;
each Y1 is independently CH or N;
each Z1 is independently -NR1D-, -O-, or -S-;
each Y2 is independently CH or N;
each Z2 is independently -NR1D-, -O-, or -S-;
each R30 is independently H or C1-C6 alkyl;
each L3 is independently C1-C6 alkylene, C3-C7 cycloalkylene, 3- to 7-membered heterocyclylene, or 5- or 6-membered heteroarylene;
m1 is 1, 2, 3, or 4;
each Y3 is independently CH or N;
each Z3 is independently -NR1D-, -O-, or -S-;
each Y4 is independently CH or N;
each Z4 is independently -NR1D-, -O-, or -S-;
n1 is 0, 1, or 2;
W2 is H, C1-C6 alkyl, C(O)NR1ER1F, or (AA)1-10;
each R1D is independently H, C1-C50 alkyl, C1-C50 heteroalkyl, or PEG1-50;
each R1E is independently H, C1-C50 alkyl, C1-C50 heteroalkyl, or PEG1-50;
each R1F is independently H, C1-C20 alkyl, C1-C20 heteroalkyl, PEG1-20 or one or more independently selected AA; and
each AA is independently a naturally occurring amino acid;
(b) a second terminus comprising any one of the following formulas:
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or
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Formula (12-A)
or a pharmaceutically acceptable salt thereof,
wherein:
each R20 is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C50 hydroxyalkyl;
z1 is 1, 2, 3, or 4;
each R21 is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C50 hydroxyalkyl;
z2 is 1, 2, 3, or 4;
each R22 is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C50 hydroxyalkyl; and
z3 is 1, 2, 3, or 4; and
(c) an oligomeric backbone comprising a linker between the first terminus and the second terminus.
Appropriate correction is required. See MPEP § 2173.02.
Claim 4 is objected to because of the following informalities: for brevity, 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 transcription modulator molecule of claim 1, wherein the first terminus comprises a compound of Formula (A-3):
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Formula (A-3)
or a pharmaceutically acceptable salt thereof,
wherein:
each AA is independently a naturally occurring amino acid selected from the group consisting of b-alanine, arginine, and lysine.
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
each Z1 is independently -NR1D-;
each Z2 is independently -NR1D-;
each Z3 is independently -NR1D-;
each Z4 is independently -NR1D-; and
each R1D is independently C1-C6 alkyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
each Y1 is independently N;
each Y2 is independently CH or N;
each Y3 is independently N;
each Y4 is independently CH or N.
Appropriate correction is required. See MPEP § 2173.02.
Claim 15 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 transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof, wherein the linker between the first terminus and the second terminus comprised within the oligomeric backbone has a length of less than 50 Angstroms.
Appropriate correction is required. See MPEP § 2173.02.
Claim 17 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 transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof, wherein the linker between the first terminus and the second terminus comprised within the oligomeric backbone has between 5 and 50 chain atoms.
Appropriate correction is required. See MPEP § 2173.02.
Claim 18 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 transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof, wherein the linker between the first terminus and the second terminus comprised within the oligomeric backbone contains a multimer having from 2 to 50 spacing moieties; and further wherein:
each spacing moiety is independently C1-C12 alkylene, -[(CR3aR3b)xNR4a]y-, -[(CR3aR3b)xO]y-, C2-C10 alkenylene, -[(CR3aR3b)x-CH=CH-[(CR3aR3b)xO]y-, C2-C10 alkynylene, -C(O)-, -C(O)NR4a-, -NR4a-, -NR4aC(O)-, -O-, C3-C7 cycloalkylene, 4- to 10-membered heterocycloalkylene, C6-C10 arylene, 5- to 10-membered heteroarylene, or an amino acid residue;
each R3a is independently alkyl, alkenyl, alkynyl, C(O)alkyl, C(O)alkenyl, C(O)NH2, C(O)NHalkyl, C(O)N(alkyl)2, C(O)OH, C(O)Oalkyl, C(O)Oalkenyl, C(O)Ocycloalkyl, C(O)Oheterocyclyl, C(O)Oaryl, C(O)Oheteroaryl, C(O)cycloalkyl, C(O)heterocyclyl, C(O)aryl, C(O)heteroaryl, NH2, NHC(O)alkyl, NHC(O)alkenyl, NHC(O)cycloalkyl, NHC(O)heterocyclyl, NHC(O)aryl, NHC(O)heteroaryl, O(alkyl), OC(O)alkyl, OC(O)alkenyl, OC(O)cycloalkyl, OC(O)heterocyclyl, OC(O)aryl, OC(O)heteroaryl, S(alkyl), S(O)2alkyl, S(O)2alkenyl, S(O)2cycloalkyl, S(O)2heterocyclyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
each R3b is independently alkyl, alkenyl, alkynyl, C(O)alkyl, C(O)alkenyl, C(O)NH2, C(O)NHalkyl, C(O)N(alkyl)2, C(O)OH, C(O)Oalkyl, C(O)Oalkenyl, C(O)Ocycloalkyl, C(O)Oheterocyclyl, C(O)Oaryl, C(O)Oheteroaryl, C(O)cycloalkyl, C(O)heterocyclyl, C(O)aryl, C(O)heteroaryl, NH2, NHC(O)alkyl, NHC(O)alkenyl, NHC(O)cycloalkyl, NHC(O)heterocyclyl, NHC(O)aryl, NHC(O)heteroaryl, O(alkyl), OC(O)alkyl, OC(O)alkenyl, OC(O)cycloalkyl, OC(O)heterocyclyl, OC(O)aryl, OC(O)heteroaryl, S(alkyl), S(O)2alkyl, S(O)2alkenyl, S(O)2cycloalkyl, S(O)2heterocyclyl, S(O)2aryl, S(O)2heteroaryl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
each R4a is independently H or C1-C6 alkyl;
each x is independently 2, 3, or 4; and
each y is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
Appropriate correction is required. See MPEP § 2173.02.
Claim 25 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 transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof, wherein the linker between the first terminus and the second terminus comprised within the oligomeric backbone contains -CH2C(O)NR”-(CH2)qNR’-(CH2)qNR”-C(O)(CH2)x-C(O)NR”-A-, -(CH2)xC(O)NR”-(CH2CH2O)y(CH2)x-C(O)NR”-A-, --(CH2)xO-(CH2CH2O)y-(CH2)xNR”-C(O)(CH2)x-A-, -C(O)NR”-(CH2)qNR’-(CH2)qNR”-C(O)(CH2)x-A-, or -NR”C(O)-CH2C(O)NR”-(CH2)xO(CH2CH2O)y(CH2)x-A-; and further wherein:
R’ is CH3;
R” is H;
each A is independently a bond, C1-C12 alkylene, C3-C7 cycloalkylene, 5- to 10-membered heterocycloalkylene, C6-C10 arylene, or 5- to 10-membered heteroarylene;
each q is independently 2, 3, 4, 5, 6, 7, 8, 9, or 10;
each x is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and
y is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
Appropriate correction is required. See MPEP § 2173.02.
Claim 29 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 transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof, wherein the linker between the first terminus and the second terminus comprised within the oligomeric backbone is joined with the second terminus with a moiety comprising C1-C12 alkylene, -C(O)-, -C(O)NR1a-, -NR1a-, or -NR1aC(O)-; and further wherein:
R1a is C1-C12 alkylene, C2-C10 alkenylene, C2-C10 alkynylene, C3-C7 cycloalkylene, 4- to 10-membered heterocyclylene, C6-C10 arylene, or 5- to 10-membered heteroarylene.
Appropriate correction is required. See MPEP § 2173.02.
Claim 31 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 transcription modulator molecule of claim 1, wherein the linker between the first terminus and the second terminus comprised within the oligomeric backbone is joined with the second terminus with a moiety comprising (a), (b), or (c);
(a) a structure of formula (C-1):
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Formula (C-1)
or a pharmaceutically acceptable salt thereof,
wherein:
Ring D is absent, heterocycloalkylene, or arylene;
L1 is absent, -CH2-, -CH2CH2-, -C≡C-, or -C≡C-C≡C-;
X3 is CH or N;
X4 is CH or N;
p is 0, 1, 2, or 3; and
** is the point of attachment to the second terminus; or
(b) a structure of formula (C-2):
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Formula (C-2)
or a pharmaceutically acceptable salt thereof,
wherein:
X5 is CH or N;
X6 is CH or N;
L1 is absent, -CH2-, -CH2CH2-, -C≡C-, or -C≡C-C≡C-;
X4 is CH or N; and
** is the point of attachment to the second terminus; or
(c) a structure of formula (C-3):
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Formula (C-3)
or a pharmaceutically acceptable salt thereof,
wherein:
R27 is C1-C50 alkyl, C1-C50 heteroalkyl, C(O)C1-C50 alkyl, or C(O)C1-C50 heteroalkyl;
each R1G is independently H or C1-C3 alkyl;
r1 is 1, 2, or 3;
p1 is 0, 1, 2, or 3; and
** is the point of attachment to the second terminus.
Appropriate correction is required. See MPEP § 2173.02.
Claim 54 is objected to because of the following informalities: for brevity, 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 transcription modulator molecule of claim 1, wherein the second terminus is of Formula (12-A):
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Formula (12-A)
or a pharmaceutically acceptable salt thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 55 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The transcription modulator molecule of claim 54, wherein the second terminus is of Formula (12-B) or Formula (12C):
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Formula (12-B)
or
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Formula (12-C)
or a pharmaceutically acceptable salt thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 60 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The transcription modulator molecule of claim 1, wherein the transcription modulator molecule is selected from the group consisting of:
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and
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,
or a pharmaceutically acceptable salt thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 61 is objected to because of the following informalities: for clarity and precision and, the existing recitation should be replaced with the following recitation:
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a transcription modulator molecule of claim 1, or a pharmaceutically acceptable salt thereof.
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.
Substituted transcription modulator molecules of the Formula (A-2)
Claims 1, 4, 6, 8, 15, 17, 18, 25, 29, 31, 54, 55 and 61 are rejected under 35 U.S.C. § 112(a) because the specification, while being enabling for substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are as presented herein in the section above entitled Claim Objections, does not reasonably provide enablement for substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections. 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 the invention commensurate in scope with these claims. Substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections, as recited in claim 1, have 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 substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections.
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 substituted transcription modulator molecules of the Formula (A-2), shown to the right;
(b) Nature of the invention - the nature of the invention is evaluation of substituted transcription modulator molecules of the Formula (A-2), shown to the right above;
(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). Moreover, WO 22/150555 provides a synthesis of the instantly recited substituted transcription modulator molecules of the Formula (A-2) {Ansari, et al. WO 22/150555, 2022};
(d) Level of one of ordinary skill in the art - the artisans synthesizing the inventor’s or joint inventor’s substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections, 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 unclear based on the combination of the instant specification, and Ansari, et al. in WO 22/150555, whether the instantly recited substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections, are enabled. Moreover, the following excerpt is taken from Dörwald, which has relevance to the synthesis of substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) 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).
(f) Amount of direction provided by the inventor - the invention lacks direction with respect to making and/or using substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections;
(g) Existence of working examples - the inventor or joint inventor has provided sufficient guidance to make and/or use substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are as presented herein in the section above entitled Claim Objections; however, the disclosure is insufficient to allow extrapolation of the limited examples to enable the instantly recited substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections. The specification lacks working examples of substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections.
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 or use 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). Similarly, the specification, as originally filed, including any references incorporated therein, fails to provide the necessary support required by 35 U.S.C. § 112(a) to enable the instantly recited substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections. Thus, it is unclear, based on the guidance provided by the specification, whether a substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections, such as N-(5-((3-((2-((1-((2R,6S)-4-(2-(4-(1-(3-methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-1,28-dioxo-3,6,9,12,15,18,21,24-octaoxa-27-azatriacontan-30-yl)carbamoyl)-1-methyl-1H-imidazol-4-yl)amino)-3-oxopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-(1-(1-methyl-4-(1-methyl-1H-imidazole-2-carboxamido)-1H-pyrrole-2-carbonyl)pyrrolidine-3-carboxamido)-1H-imidazole-2-carboxamide, shown to the left above, is synthetically feasible.
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 substituted transcription modulator molecules of the Formula (A-2), where the substituted transcription modulator molecules of the Formula (A-2) are not as presented herein in the section above entitled Claim Objections, 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 1, 4, 6, 8, 15, 17, 18, 25, 29, 31, 54, 55 and 61 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 the phrase, optionally substituted, in claim 1, with regard to L3, W1, W2, R1D, R1E, and/or R1F, respectively, is a relative phrase which renders the claims indefinite. The phrase, optionally substituted, 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, on pages 157-158, uses open language, such as include, without limitation, to define the phrase, optionally substituted, using a boiler plate list of functional groups, such as lower alkyl, etc., and further discloses that the substituents themselves may be further substituted; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted transcription modulator molecules of the Formula (A-2) have been rendered indefinite by the use of the phrase, optionally substituted, with regard to L3, W1, W2, R1D, R1E, and/or R1F, 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.
Claim 15 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 term, about, is a relative term which renders the claim indefinite. The term, about, 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 term, about. Similarly, the meaning of a term 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 transcription modulator molecules of the Formula (A-2) have been rendered indefinite by the use of the term, about. {See Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir.2007); W. L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983); Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991); 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 18 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, optionally substituted, with regard to the spacing moiety, R3a, R3b, and/or R4a, respectively, is a relative phrase which renders the claim indefinite. The phrase, optionally substituted, 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, on pages 157-158, uses open language, such as include, without limitation, to define the phrase, optionally substituted, using a boiler plate list of functional groups, such as lower alkyl, etc., and further discloses that the substituents themselves may be further substituted; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted transcription modulator molecules of the Formula (A-2) have been rendered indefinite by the use of the phrase, optionally substituted, with regard to the spacing moiety, R3a, R3b, and/or R4a, respectively.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 25 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, optionally substituted, with respect to A, is a relative phrase which renders the claim indefinite. The phrase, optionally substituted, 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, on pages 157-158, uses open language, such as include, without limitation, to define the phrase, optionally substituted, using a boiler plate list of functional groups, such as lower alkyl, etc., and further discloses that the substituents themselves may be further substituted; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted transcription modulator molecules of the Formula (A-2) have been rendered indefinite by the use of the phrase, optionally substituted, with respect to A.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 29 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 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 29 recites the broad limitation, C1-12 alkylene, with respect to R1a, and the claim also recites C1-6 alky, with respect to R1a, 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).
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this section of the rejection.
Then, the inventor or joint inventor should further note that claim 29 recites the limitation, H, with respect to R1a, where the limitation is implausible, resulting in an incomplete valence. Claims are unduly speculative where they define only a portion of a substituted transcription modulator molecule of the Formula (A-2). Consequently, since incomplete valences are not permitted in the structure of the substituted transcription modulator molecules of the Formula (A-2), an essential portion of the substituted transcription modulator molecules of the Formula (A-2) is indefinite and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the substituted transcription modulator molecules of the Formula (A-2). {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 section of the rejection.
Moreover, the inventor or joint inventor should further note that the phrase, optionally substituted, with respect to R1a, is a relative phrase which renders the claim indefinite. The phrase, optionally substituted, 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, on pages 157-158, uses open language, such as include, without limitation, to define the phrase, optionally substituted, using a boiler plate list of functional groups, such as lower alkyl, etc., and further discloses that the substituents themselves may be further substituted; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted transcription modulator molecules of the Formula (A-2) have been rendered indefinite by the use of the phrase, optionally substituted, with respect to R1a.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this section of the rejection.
Claim 31 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, optionally substituted, with respect to R27, is a relative phrase which renders the claim indefinite. The phrase, optionally substituted, 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, on pages 157-158, uses open language, such as include, without limitation, to define the phrase, optionally substituted, using a boiler plate list of functional groups, such as lower alkyl, etc., and further discloses that the substituents themselves may be further substituted; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted transcription modulator molecules of the Formula (A-2) have been rendered indefinite by the use of the phrase, optionally substituted, with respect to R27.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 54 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, optionally substituted, with regard to R20, R21, and/or R22, respectively, is a relative phrase which renders the claim indefinite. The phrase, optionally substituted, 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, on pages 157-158, uses open language, such as include, without limitation, to define the phrase, optionally substituted, using a boiler plate list of functional groups, such as lower alkyl, etc., and further discloses that the substituents themselves may be further substituted; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the substituted transcription modulator molecules of the Formula (A-2) have been rendered indefinite by the use of the phrase, optionally substituted, with regard to R20, R21, and/or R22, respectively.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim Rejections - 35 U.S.C. § 112(d)
The following is a quotation of the fourth paragraph of 35 U.S.C. § 112:
(d) REFERENCE IN DEPENDENT FORMS. Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. § 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The inventor or joint inventor should note that claim 4 recites the limitation, The transcription modulator molecule of claim,…, in line 1 of the claim.
Similarly, the inventor or joint inventor should further note that [S]ubject to U.S.C. § 112(e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed.
Likewise, the inventor or joint inventor should further note that since The transcription modulator molecule of claim,…, fails to specify a further limitation to the substituted transcription modulator molecules of the Formula (A-2), as recited in claim 1, and/or fails to include all the limitations of the substituted transcription modulator molecules of the Formula (A-2), as recited in claim 1, the instant dependent claim is rendered improperly dependent under 35 U.S.C. § 112(d).
Next, the inventor or joint inventor should further note that the U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of 35 U.S.C. § 112(d) are related to matters of form, non-compliance with 35 U.S.C. § 112(d) renders the claim unpatentable just as non-compliance with other subsections of 35 U.S.C. § 112 would. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)}.
Moreover, the inventor or joint inventor should further note that if a dependent claim does not comply with the requirements of 35 U.S.C. § 112(d) the dependent claim should be rejected under 35 U.S.C. § 112(d) as unpatentable rather than objecting to the claim. {See also MPEP § 608.01(n), Section III, Infringement Test for dependent claims}.
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.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624
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