DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ preliminary amendment, filed on 06/18/2024, in which claims 2, 11-12, 15-16, 18, 20, 29-30, 33, and 35-36 are amended and claims 3-10, 13-14, 21-28, 31-32, and 38-69 are cancelled.
Claims 1-2, 11-12, 15-20, 29-30, and 33-37 are pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/CN2022/140288 filed on 12/20/2022, which claims foreign priority to CHINA PCT/CN2021/139736 filed on 12/20/2021.
Information Disclosure Statement
The information disclosure statement (IDS) dated 06/18/2024 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 11-12, 15-20, 29-30, and 33-37 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrase “voltage-gated potassium channel (KCNB2) inhibitor” is recited in claim 1 line 4, claim 2 line 6, claim 11 line 5, claim 12 lines 4 and 7, claim 16 line 6, claim 17 line 3, claim 19 line 3, claim 20 line 6, claim 29 line 5, claim 30 lines 4 and 7, claim 33 line 6, and claim 34 line 3. It is not clear whether the narrower recitation of the specific voltage-gated potassium channel KCNB2 recited in the parenthetical is used to limit the broader recitation of the genus of voltage-gated potassium channels or provide an optional example. Thus, it is unclear whether the limitation “KCNB2” in the parenthetical is part of the claimed invention. For purposes of compact prosecution, under broadest reasonable interpretation, the claim will be interpreted as requiring an inhibitor of any voltage-gated potassium channel.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 19-20, 29, and 36-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuijpers et al. (Dermatology, 1997; PTO-892).
Kuijpers discloses cases studies of combination therapy with Acitretin and cyclosporin A in patients with erythrodermic psoriasis. Kuijpers discloses that three patients with psoriatic erythroderma, who did not respond to monotherapy with acitretin in adequate dosages, were treated with combined therapy consisting of acitretin and cyclosporin A (page 88, paragraph 2). The cases studies include Case 2, for whom cyclosporin A 3 mg/kg/day was combined with acitretin 0.4 mg/kg/day (page 88, paragraph 5).
Regarding the limitation “wherein the combination is used for the treatment of amyotrophic lateral sclerosis” of instant claim 19, It is noted that Kuijpers does not provide an embodiment of the composition used in the manner instantly claimed, administered to a subject for the treatment of amyotrophic lateral sclerosis. However, these cited recitations are considered an “intended use” of the claimed composition. The “intended use” of the claimed composition does not patentably distinguish the composition, per se, since such disclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Regarding claim 36, the limitation comprising the combination of claim 19 and “an instruction for use, wherein the instruction describes the use of the combination or the pharmaceutical composition for treating amyotrophic lateral sclerosis”, constitutes a limitation of written instructions. Inclusion of instructions in a kit is not considered a novel step in the case where no functional relationship exists between the printed matter and the product. MPEP 2111.05(b) states that in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. Thus, the limitations of claim 36 are obvious over any prior art teaching the combination of claim 19.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Arakawa et al. (US 2008/0027039 A1; PTO-892).
Arakawa discloses methods of treating motor neuron diseases comprising administering a serotonin receptor antagonist together with a pharmaceutically acceptable carrier (abstract). Specifically, Arakawa teaches that 5HT participates in the selective falling-off of motor neuron cells in amyotrophic lateral sclerosis (ALS) [0008], and that 5-hydroxytryptophan (5HTP), which is a 5HT precursor, prolongs the life of ALS model mice [0009]. Arakawa discloses that compounds having serotonin receptor antagonist activity, particularly 5HT1A receptor antagonists and 5HT2A receptor antagonists, can inhibit excessive excitation of motor neuron cells and can be therapeutic agents for motor neuron diseases, particularly therapeutic agents for ALS that can inhibit neurodegeneration [0016]. Compounds having anticoagulant activity and antidepressant activity are also known to have 5HT2A receptor antagonist activity and thus anticoagulants and antidepressants are also usable as therapeutic agents for motor neuron diseases. Arakawa teaches that suitable antidepressants include, among others, mirtazapine [0158]. Arakawa teaches that the compound having serotonin receptor antagonist activity may be used as a part of a combination with other medicaments [0203].
The teachings of Arakawa differ from that of the instantly claimed invention in that they do not disclose an embodiment of treating ALS comprising administering the claimed active agents.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to treat ALS by administering mirtazapine because it is prima facie obvious to combine the prior art elements of mirtazapine and the administration of a serotonin receptor antagonist to ALS patients to yield the predictable result of a treatment of ALS. One of ordinary skill in the art would have a reasonable expectation of success because Arakawa teaches that compounds having serotonin receptor antagonist activity, particularly 5HT2A receptor antagonists, are expected to be therapeutic agents for ALS and also teaches that mirtazapine is a 5HT2A receptor antagonist suitable as a therapeutic agent for ALS.
Claims 11-12, 15, 19-20, 29-30, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Arakawa et al. (US 2008/0027039 Al; PTO-892), as applied to claim 1, in view of Clark et al. (Expert Opinion on Drug Metabolism & Toxicology, 2020; PTO-892).
The teachings of Arakawa are discussed in detail above.
The teachings of Arakawa differ from that of the instantly claimed invention in that they do not disclose an embodiment of treating ALS comprising administering the claimed first and second active agents.
Clark discusses the state of the art in retinoic acid receptor (RAR) targeted drugs for treatment of neurodegenerative disease, focusing on the role of retinoids in modulating various signaling pathways in the brain (abstract). Retinoid’s unique properties in inducing neurite outgrowth, promoting neuronal survival and regulating proteostasis have prompted interest in the use of synthetic retinoid compounds across a range of neurodegenerative conditions including AD, ALS and PD (page 1102, paragraph 3). Proteostasis dysregulation also increasingly appears to be involved in ALS, specifically in reference to impaired protein degradation. Retinoids appear to have a key role in the maintenance of proteostasis. Most notably, retinoic acid (RA) exhibits neuroprotective effects in cultured neuroblastoma cells under UPS inhibition, a state mirroring the cellular environment of the ALS pathology (paragraph bridging pages 1102-1103). The initial suggestion that RAR ligands may be therapeutic for ALS arose from the observation that RA signaling may be disrupted and possibly deficient in the disease pathology (page 1103, paragraph 1). In discussing synthetic retinoids, Clark teaches that etretinate and acitretin make up the second-generation of retinoid compounds. Acitretin has a relatively improved safety profile over etretinate and continues to be prescribed for psoriasis treatment (page 1100, paragraph 1). Clark concludes that part of the pathology of ALS is a local decline in retinoid signaling pathways and so stimulation of retinoid signaling may be a significant route forward for the treatment of neurodegenerative diseases (page 1105, paragraph 2).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to treat ALS by administering a combination of mirtazapine and acitretin because it is prima facie obvious to combine the prior art elements of mirtazapine and acitretin according to known methods of treating ALS to yield the predictable result of a treatment of ALS. One of ordinary skill in the art would have a reasonable expectation of success because Arakawa, as discussed above, suggests the treatment of ALS using mirtazapine, and Clark teaches acitretin as a synthetic retinoid and suggests stimulation of retinoid signaling by synthetic retinoids for the treatment of neurodegenerative diseases including ALS. Furthermore, Arakawa teaches that the compound having serotonin receptor antagonist activity may be used as a part of a combination with other medicaments.
Regarding claim 15, it would have been prima facie obvious for one of ordinary skill in the art to administer the mirtazapine and acitretin simultaneously, separately, and sequentially because it is obvious to choose from a finite number of predictable solutions, and the mirtazapine and acitretin would have been administered either simultaneously, separately, or sequentially.
Regarding claim 35, Arakawa discloses methods of treating motor neuron diseases comprising administering a serotonin receptor antagonist together with a pharmaceutically acceptable carrier (abstract).
Regarding claim 36, the limitation comprising the combination of claim 19 and “an instruction for use, wherein the instruction describes the use of the combination or the pharmaceutical composition for treating amyotrophic lateral sclerosis”, constitutes a limitation of written instructions. Inclusion of instructions in a kit is not considered a novel step in the case where no functional relationship exists between the printed matter and the product. MPEP 2111.05(b) states that in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. Thus, the limitations of claim 36 are obvious over any prior art teaching the combination of claim 19.
Regarding claim 37, the combined teachings of Arakawa and Clark teaches the active agents of the claimed kit which would necessarily have to exist in the same or separate containers.
Claims 16-18 and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Arakawa et al. (US 2008/0027039 Al; PTO-892) view of Clark et al. (Expert Opinion on Drug Metabolism & Toxicology, 2020; PTO-892) as applied to claims 1 and 19, further in view of Corcia et al. (Drugs, 2008; PTO-892) and Wulff et al. (Chem Rev. 2008; PTO-892).
The combined teachings of Arakawa and Clark are discussed in detail above.
The combined teachings of Arakawa and Clark differ from that of the instantly claimed invention in that they do not disclose an embodiment of treating ALS comprising administering the claimed third active agent.
Corcia discloses the state of the art in the management of amyotrophic (ALS) lateral sclerosis (abstract). Corcia teaches that cramps occur in the initial stages of ALS. The cramps can be managed using correct hydration and manual stretching. The most frequently used drug is
quinine sulfate (200 mg twice daily) promoted by clinical practices in ALS management (page 1042, paragraph 9).
Wulff discusses the state of the art in K+ channel modulators for the treatment of neurological disorders and autoimmune diseases (page 6, paragraph 3). Table 1 on page 56 teaches that Quinine is an inhibitor of the Kv2.2 channel, which corresponds to KCNB2.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to treat ALS by administering a combination of quinine, mirtazapine, and acitretin because it is prima facie obvious to combine the prior art elements of quinine, mirtazapine, and acitretin according to known methods of treating ALS to yield the predictable result of a treatment of ALS. One of ordinary skill in the art would have a reasonable expectation of success because Arakawa suggests the treatment of ALS using mirtazapine, Clark teaches acitretin as a synthetic retinoid and suggests stimulation of retinoid signaling by synthetic retinoids for the treatment of neurodegenerative diseases including ALS, and Corcia teaches that Quinine is used in the clinical treatment of ALS. Furthermore, Arakawa teaches that the compound having serotonin receptor antagonist activity may be used as a part of a combination with other medicaments.
Conclusion
No claims are allowed.
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/S.G.H./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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