Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Instant application 18/563,916 filed on 11/24/2023 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
Claims 1-6 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/24/2023 was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 2 is objected to because of the following informalities:
Claim 2 recite “muscular dystrophy” twice.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Although enabled for treatment of muscle diseases the claims are not enabled for prevention of muscle diseases. This is scope of enablement rejection.
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) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill;(E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure (MPEP 2164).
The instant claims are very broad, directed to both preventing and treating muscle diseases.
Further, the instant claims recite multiple muscle diseases: sarcopenia, muscular atrophy, myasthenia, muscular dystrophy, myotonia, hypotonia, muscular weakness, muscular dystrophy, amyotrophic lateral sclerosis, and inflammatory myopathy (see instant claim 2). The recited diseases comprise distinct etiology and pathophysiology. As evidenced by NIH (NIH: Inflammatory Myopathies National Institute of Neurological Disorders and Stroke and as evidenced by NIH: Amyotrophic Lateral Sclerosis (ALS) | National Institute of Neurological Disorders and Stroke, printed 2/14/2026): for example, myopathies are muscle-destroying inflammation (etiology: autoimmune/inflammatory) while ALS is a nerve-destroying disease (etiology: largely idiopathic).
With respect to the definition of “prevention”, the claims are given their broadest reasonable interpretation.
The Oxford English Dictionary defines the verb “to prevent” as “to preclude the occurrence of (an anticipated event, state, etc.); to render (an intended, possible, or likely action or event) impractical or impossible by anticipatory action; to put a stop to” (definition II.9.a). “Preventing” as recited in the instant claims, is interpreted to mean the complete and total blocking of all symptoms of a muscle disease for an indefinite period of time. Merely making the disease less likely would not render the disease impossible and thus not qualify as preventing.
In order to prevent a disease: one would need to precisely identify those subjects likely to acquire such a disease, administer Applicant’s claimed invention, and demonstrate that the patient did not develop the disease as a result of the administration of the claim invention. The instant specification does not provide any guidance for selecting a population.
A disclosure should contain representative examples which provide reasonable assurance to one skilled in the art that ensure that the inventor had possession, as of the filling date of the application, of the specific subject matter claimed by him.
It should be noted that homoharringtonine is a known, natural alkaloid that is approved for treating chronic myeloid leukemia (Kantarjian et al., Clin Lymphoma Myeloma Leukemia. (2013) 13:530–3).
Regarding amyotrophic lateral sclerosis (ALS), prior art teaches “several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results” (Dorst et al., Ther Adv Neurol Disord 2018, Vol. 11: 1–16). Moreover, prior art fails to teach ALS prevention. Unfortunately, there is currently no way to prevent most neuromuscular disorders.
As evidenced by NIH (NIH: Inflammatory Myopathies National Institute of Neurological Disorders and Stroke and as evidenced by NIH: Amyotrophic Lateral Sclerosis, printed 2/14/2025) “Nearly all cases of ALS are considered sporadic, meaning the disorder seems to happen at random with no clearly associated risk factors and no family history. Although family members of people with ALS are at an increased risk for the disorder the overall risk is very low—most won’t develop ALS.”
Further, prevention of a disease is a significant challenge, most individuals eligible for the preventive treatment will be healthy and asymptomatic, and the use of medicines with side effects will need to be justify in terms of the risk–benefit ratio.
The instant specification has provided no working examples of preventing any muscle diseases. The only information in the specification are data related to gain in muscle strength (see instant specification, Example 2) and treatment of muscular atrophy (instant specification, Example 3).
Further, the specification does not provide any guidance for selecting a population or any data about risk-benefit ratio for treatments of healthy subjects.
Furthermore, the specification does not provide directions about the length of the preventive treatment. Prevention of a disease is not the same as treatment. In order to prevent a disease, as opposed to merely delaying or reducing symptoms, a method must either render the subject completely resistant to said disease after a limited number of treatments, or, when continued indefinitely, continue to suppress the occurrence of that disease.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. The specification does not enable any skilled in the art to which it pertains, or with it is most nearly connected, to use the invention commensurate in scope with the claim. Considering the lack of guidance in the specification, one of ordinary skill in the art would be burden with undue experimentation to practice the invention commensurate in the scope of the instant claims.
Since the specification does not enable any muscle diseases prevention, the examiner suggests limiting the instant claims to methods of treating specific muscle diseases.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li et al., J Mol Med (Berl). 2008 October; 86(10): 1113–1126) in view of Liu (US-4675318 , Jan 23,1987) and in view of
Chen (Chen et al., Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2220-2225).
Li teaches that nuclear factor-kappa B (NF-κB) is one of most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions, including muscular dystrophy (abstract). Further, Li teaches activation of NF-κB in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy (abstract).
Furthermore, Li teaches” it is clear that NF-κB can induce muscle loss by multiple mechanisms and inhibition of NF-κB activity has enormous potential for the prevention and treatment of muscle-wasting not only in chronic diseases but also in many conditions such as unloading, denervation, space flight, aging etc.”
Regarding, muscular dystrophy, Li teaches inhibition of NF-κB with pyrrolidine dithiocarbamate (PDTC) or IRFI-042 (see page 7/4.1 Muscular Dystrophy, third paragraph):
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Moreover, Li teaches “it is important to recognize that at present glucocorticoid therapy (prednisone) is the only effective pharmacologic treatment that increases muscle strength and function, improves pulmonary function, and significantly slows the progression of weakness in DMD patients. Interestingly, glucocorticoids are also one of the most important known inhibitors of NF-κB” (see page 7/4.1 Muscular Dystrophy, third paragraph).
Li is silent about homoharringtonine or pharmaceutical composition comprising homoharringtonine for treating muscle diseases.
Liu teaches and claims pharmaceutical composition comprising homoharringtonine (see claim 1):
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Regarding instant claim 3, it should be noted that Liu teaches overlapping ranges.
Liu is also silent about homoharringtonine or pharmaceutical composition comprising homoharringtonine for treating muscle diseases.
Chen teaches homoharringtonine (HHT) binds to and inhibits NF-kB repressing factor (NKRF), thereby inhibiting NF-kB (see abstract and Figure 4):
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Since Li teaches that inhibition of NF-κB activity has enormous potential for treatments of loss of skeletal muscle mass in various physiological and pathophysiological conditions, including in muscular dystrophy, and Chen teaches homoharringtonine inhibits NF-κB - Applying KSR prong (B) - Simple substitution of one known element for another to obtain predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the inhibitors of NF-κB disclosed by Li, e.g. glucocorticoid therapy, PDTC or IRFI-042, with an alternative NF-κB inhibitor, such as homoharringtonine with a reasonable expectation of success because Chen teaches homoharringtonine inhibits NF-κB.
One of ordinary skill would be motivated by the teachings of Li and Chen and would expect improvement in muscle strength after administration of pharmaceutical composition comprising homoharringtonine.
Regarding claim 4, Chen teaches administering a therapeutically effective amount of HHT (see supplementary information, Animal model, Pages 7/8). The therapeutically effective amount of HHT taught by Chen reads on the “administering a pharmaceutical composition comprising homoharringtonine” recited in the instant claims. The recited properties (such as the inhibition of muscle loss and increase in muscle strength without a change in body weight) that accrue from a process step of administering HHT to a subject in need are considered characteristic features of the claimed therapeutic method.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
In the present case the burden is shifted to Applicant to prove that the administered therapeutically effective amount of HHT in the therapeutic regimen of Li, Liu and Chen will not inhibit muscle loss and not increase muscle strength without a change in body weight.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li et al., J Mol Med (Berl). 2008 October; 86(10): 1113–1126) in view of Liu (US-4675318) and in view of Chen (Chen et al., Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2220-2225) and further in view of WO-2019078381- A1.
The teachings of Li, Liu and Chen have been discussed above and those teachings are incorporated herein by reference.
The combination of teachings of Li, Liu and Chen is silent about health food composition comprising homoharringtonine (HHT).
WO-2019078381-A1 teaches pharmaceutical composition, a food composition, and a food additive for the prevention and treatment or improvement of muscle loss, muscle weakness, and muscle atrophy (see abstract and paragraphs [0065] - [0067]).
It should be noted that WO-2019078381-A1 teaches the compositions contain Enterococcus faecalis (does not contain homoharringtonine (HHT).
However, since Li teaches that inhibition of NF-κB activity has enormous potential for treatments of loss of skeletal muscle mass in various physiological and pathophysiological conditions, including in muscular dystrophy, and Chen teaches homoharringtonine inhibits NF- κB - Applying KSR prong (B) - Simple substitution of one known element for another to obtain predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the inhibitors of NF-κB disclosed by Li, e.g. glucocorticoid therapy, PDTC or IRFI-042, with homoharringtonine with a reasonable expectation of success because Chen teaches homoharringtonine inhibits NF-κB.
One of ordinary skill would be motivated by the teachings of Li and Chen and would expect improvement in muscle strength. Further, WO-2019078381-A1 teaches food compositions are useful method for administering drugs for prevention and improvement of muscle weakness related diseases. Therefore, one of ordinary skill would be motivated to prepare a health food comprising muscle wasting treating homoharringtonine of Li, Liu and Chen above, because food compositions allow for a patient-friendly method of administering active therapeutic agents to treat muscle weakness related diseases.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm.
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/I.S./Examiner, Art Unit 1621
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621