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 1-19 are pending in the instant invention. According to the Listing of Claims, filed June 6, 2024, claims 1-7 were amended and claims 9-19 were added.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/EP2022/086773, filed December 19, 2022, which claims priority under 35 U.S.C. § 119(a-d) to EP 21306863.8, filed December 20, 2021.
Restrictions / Election of Species
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The forthcoming first Office action and prosecution on the merits includes (1) claims 1 and 3-12, drawn to a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, shown to the right above, or a pharmaceutically acceptable solvate thereof; (2) claims 2 and 13-19, drawn to a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutyl-amino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, shown to the right above, or a pharmaceutically acceptable solvate thereof, respectively.
Thus, a first Office action and prosecution on the merits of claims 1-19 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.
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 method for treating a motor neuron disease or neuromuscular junction disorder in a patient, wherein the method comprises administering to the patient in need thereof a therapeutically effective amount of a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I:
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Formula I
or a pharmaceutically acceptable solvate thereof,
wherein:
x is in the range of 1 to 4;
wherein the motor neuron disease or neuromuscular junction disorder is selected from the group consisting of a disorder of the motor units resulting from an accident, Eaton-Lambert syndrome, hereditary spastic paraplegia (HSP), monomelic amyotrophy, myasthenia gravis, neurolathyrism, non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, post-irradiation syndrome, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), Sandhoff disease, spinal-bulbar muscular atrophy (SBMA), stiff-person syndrome, and Tay-Sachs disease.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 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 delaying the onset of a motor neuron disease or neuromuscular junction disorder in a patient, wherein the method comprises administering to the patient in need thereof a therapeutically effective amount of a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I:
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Formula I
or a pharmaceutically acceptable solvate thereof,
wherein:
x is in the range of 1 to 4;
wherein the motor neuron disease or neuromuscular junction disorder is selected from the group consisting of a disorder of the motor units resulting from an accident, Eaton-Lambert syndrome, hereditary spastic paraplegia (HSP), monomelic amyotrophy, myasthenia gravis, neurolathyrism, non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, post-irradiation syndrome, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), Sandhoff disease, spinal-bulbar muscular atrophy (SBMA), stiff-person syndrome, and Tay-Sachs disease.
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 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 method according to claim 1, wherein x is in the range of 1 to 2.
Appropriate correction is required. See MPEP § 2173.02.
Claim 4 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 according to claim 3, wherein x is 1.5.
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 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 according to claim 1, wherein the motor neuron disease or neuromuscular junction disorder is selected from the group consisting of a disorder of the motor units resulting from an accident, Eaton-Lambert syndrome, hereditary spastic paraplegia (HSP), monomelic amyotrophy, myasthenia gravis, non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), and spinal-bulbar muscular atrophy (SBMA).
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 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 according to claim 6, wherein the motor neuron disease is selected from the group consisting of hereditary spastic paraplegia (HSP), non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), and spinal-bulbar muscular atrophy (SBMA).
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 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 according to claim 7, wherein the motor neuron disease is non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 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 according to claim 4, wherein the sequi-succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine is a crystalline form characterized by an X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at diffraction angles (º2q) selected from the group consisting of 3.8º ± 0.2º, 10.3º ± 0.2º, 12.4º ± 0.2º, 16.2º ± 0.2º, 17.9º ± 0.2º, 19.8º ± 0.2º, 20.4º ± 0.2º, 23.8º ± 0.2º, and 26.7º ± 0.2º.
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 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 according to claim 9, wherein the motor neuron disease or neuromuscular junction disorder is selected from the group consisting of a disorder of the motor units resulting from an accident, Eaton-Lambert syndrome, hereditary spastic paraplegia (HSP), monomelic amyotrophy, myasthenia gravis, non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), and spinal-bulbar muscular atrophy (SBMA).
Appropriate correction is required. See MPEP § 2173.02.
Claim 11 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 according to claim 10, wherein the motor neuron disease is selected from the group consisting of hereditary spastic paraplegia (HSP), non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), and spinal-bulbar muscular atrophy (SBMA).
Appropriate correction is required. See MPEP § 2173.02.
Claim 12 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 according to claim 11, wherein the motor neuron disease is non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis.
Appropriate correction is required. See MPEP § 2173.02.
Claim 13 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 method according to claim 2, wherein x is in the range of 1 to 2.
Appropriate correction is required. See MPEP § 2173.02.
Claim 14 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 method according to claim 13, wherein x is 1.5.
Appropriate correction is required. See MPEP § 2173.02.
Claim 16 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 according to claim 14, wherein the sequi-succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine is a crystalline form characterized by an X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at diffraction angles (º2q) selected from the group consisting of 3.8º ± 0.2º, 10.3º ± 0.2º, 12.4º ± 0.2º, 16.2º ± 0.2º, 17.9º ± 0.2º, 19.8º ± 0.2º, 20.4º ± 0.2º, 23.8º ± 0.2º, and 26.7º ± 0.2º.
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 method according to claim 16, wherein the motor neuron disease or neuromuscular junction disorder is selected from the group consisting of a disorder of the motor units resulting from an accident, Eaton-Lambert syndrome, hereditary spastic paraplegia (HSP), monomelic amyotrophy, myasthenia gravis, non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), progressive muscular atrophy (PMA), and spinal-bulbar muscular atrophy (SBMA).
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 method according to claim 17, wherein the motor neuron disease is selected from the group consisting of hereditary spastic paraplegia (HSP), non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis, primary lateral sclerosis (PLS), progressive bulbar palsy (PBP), and spinal-bulbar muscular atrophy (SBMA).
Appropriate correction is required. See MPEP § 2173.02.
Claim 19 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 according to claim 18, wherein the motor neuron disease is non-frontotemporal degeneration (FTD) amyotrophic lateral sclerosis.
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.
(1) Method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)-propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine; and (2) Method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine
Claims 1, 2 and 6-8 are rejected under 35 U.S.C. § 112(a) because the specification, while being enabling for performing (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is in the range of 1 to 4, respectively, does not reasonably provide enablement for performing (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, 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. (1) A method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, respectively, as recited in claims 1 and 2, 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 (perform) (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, 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 (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)-propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, shown to the right below; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, shown to the right, respectively;
(b) Nature of the invention - the nature of the invention is performance of (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, shown to the right above; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine 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). Moreover, WO 22/069654, as provided in the file and cited on the IDS, illustrates the synthesis of a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, and/or methods of use thereof {Brantis, et al. WO 22/069654, 2022};
(d) Level of one of ordinary skill in the art - the artisans performing the inventor’s or joint inventor’s (1) method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutyl-amino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, 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 unclear based on the combination of the instant specification, and Brantis, et al. in WO 22/069654, as provided in the file and cited on the IDS, whether the entire scope of the instantly recited succinate salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine are enabled. Moreover, the following excerpt is taken from Dörwald, which has relevance to the synthesis of the entire scope of the instantly recited succinate salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine are enabled (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 (performing) (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, respectively;
(g) Existence of working examples - the inventor or joint inventor has provided sufficient guidance to make and/or use (perform) (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is in the range of 1 to 4, respectively; however, the disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, respectively. The specification lacks working examples of performing (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutyl-amino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, 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 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 performing the instantly recited (1) method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, respectively. Thus, it is unclear, based on the guidance provided by the specification, whether a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine, such as N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine decasuccinate salt, shown to the left, is either synthetically feasible or possesses utility as a therapeutic agent, useful in (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine, respectively.
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) (1) a method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)-piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4; and (2) a method for delaying the onset of motor neuron diseases and neuromuscular junction disorders in a patient… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, where x is not in the range of 1 to 4, 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 1 and 3-12 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 claim 1 fails to explicitly recite a target population for the method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)-propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I, which renders the claim indefinite.
Similarly, the inventor or joint inventor should further note that 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.
Likewise, the inventor or joint inventor should further note that the specification, on page 12, discloses patients as a target population; however, neither the specification, nor the claim explicitly limits the invention to this preferred embodiment.
Next, the inventor or joint inventor should further note that the method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine of the Formula I has been rendered indefinite by the lack of a target population.
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 4, 5 and 9-12 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, about, in claim 4, 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. Likewise, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine has 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)}.
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 14-19 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 term, about, in claim 14, 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. Likewise, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the method for delaying in a patient the onset of motor neuron diseases and neuromuscular junction disorders… comprising administering… a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine has 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)}.
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 Rejections - Obviousness-type Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute), so as to prevent the unjustified or improper timewise extension of the right to exclude granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined invention claim is not patentably distinct from the reference claims because the examined invention claim is either anticipated by, or would have been obvious over, the reference claims. {See In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969)}.
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Consequently, at least claims 9-12 and 16-19 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over at least claims 17 and 18 of copending US Application No. 18/044,682. Although the conflicting claims are not identical, they are not patentably distinct from each other because claim 17 in the copending invention recites a crystalline form of a succinate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)-propyl)-1H-benzo[d]imidazol-2-amine having formula II, shown to the left above, wherein x is 1.5, which is administered within the instantly recited method for treating and/or preventing motor neuron diseases and neuromuscular junction disorders… comprising administering… a crystalline form of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine sequi-succinate.
The inventor or joint inventor should note that [T]he discovery of a previously unappreciated property of a prior art compound, or of a scientific explanation for the prior art’s functioning, does not render the old compound patentably new to the discoverer. {See Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)}.
Similarly, the inventor or joint inventor should further note that [T]he claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. {See In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977); and In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004)}.
Likewise, the inventor or joint inventor should note that [W]hen the claim recites using an old compound and the use is directed to a result or property of that compound, then the claim is anticipated. {See In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978); and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966)}.
Next, the inventor or joint inventor should further note that [P]roducts of identical chemical composition may not have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties the inventor or joint inventor discloses and/or claims are necessarily present. {See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990)}.
Then, the inventor or joint inventor should further note that this is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Moreover, the inventor or joint inventor should further note that a timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 37 CFR 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground, provided the conflicting invention or patent either is shown to be commonly owned with this invention, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Furthermore, the inventor or joint inventor should also note that the USPTO internet Web site contains terminal disclaimer forms which may be used, and the inventor or joint inventor is encouraged to visit http://www.uspto.gov/forms/, where (i) the filing date of the invention will determine what form should be used, and (ii) a web-based eTerminal Disclaimer may be filled out completely online using web-screens, respectively.
Also, the inventor or joint inventor should further note that an eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission.
Finally, for more information about eTerminal Disclaimers, the inventor or joint inventor should refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
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
Prosecution Insights