DETAILED ACTION
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 .
Status of the Claims
This Office Action is in response to Applicant's Restriction Requirement remarks filed on November 22, 2025. Claim(s) 30-50 are pending. Claim(s) 30-35 and 44-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant's election of Group II drawn to a method of delaying onset of a neurodegenerative disease and election of species of Parkinson’s disease (neurodegenerative disease) without traverse of the restriction requirement in the reply is acknowledged. The requirement is deemed proper and is therefore made FINAL. Claim(s) 36-43 and 50 are examined herein insofar as they read on the elected invention and species.
Claim Rejections - 35 USC § 112, first paragraph
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 36-43 and 50 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the treatment of one or more symptoms of a neurodegenerative disease by administering a therapeutically effective amount of acetyl-leucine, wherein the neurodegenerative disease is chosen from multiple system atrophy (MSA-P/MSA-C), Parkinson's Disease, Lewy Body dementia, and frontotemporal dementia with parkinsonism, does not reasonably provide enablement for the treatment of any neurodegenerative disorder and symptoms thereof as recited in the instant claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The specification does not provide sufficient information that all the ailments in the instant claims are treatable by compounds of formula I as described in the methods claimed.
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. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404.
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.
The breadth of the claims and nature of the invention
The breadth of the instant claims is seen to encompass methods for the treatment of any neurodegenerative disorder and any symptom therefrom as recited in the instant claims.
The claims are extremely broad. Currently, there are no known agents that treat any symptom of any neurodegenerative disease all inclusively.
The state of the prior art and level of predictability in the art
Verma (Journal of Molecular Neuroscience, 2026) teaches, even as most recently, that neurodegeneration is a “systems biology” problem rather than a single-protein problem. The reference explains that because Alzheimer’s and other neurodegenerative disorders are multifactorial and complex a “one-size-fits-all” approach is insufficient to encompass the full range of disease mechanisms (page 1).
Thus, the treatment of these disorders is highly unpredictable. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The amount of direction provided by the inventor and existence of working examples.
The specification does not provide guidance for the treatment of the scope of disorders embraced by umbrella terms or any symptom of any neurodegenerative disease by administering an effective amount of acetyl-leucine of the claims.
In the instant case, applicant demonstrates the effectiveness of acetyl-leucine exemplifying improvement in symptoms including improvement in sleep, speech, improvement in motor function and improvement in gait on patients suffering from ALS, progressive ataxia, MSA-C, and parkinsonism (Examples 7-11).
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application 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. In re Wright, 27 USPQ2d 1510 (CAFC). The disclosure does not demonstrate sufficient evidence to support the Applicant's claim to the treatment/prevention. There are not sufficient working examples or data from references of the prior art to provide a nexus between those examples and a method of treating the embraced disorders with the claimed compound.
The level of one of ordinary skill.
The level of skill in the art is high (MD’s, PhD’s, or those with advanced degrees). As discussed above, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
The quantity of experimentation.
Considering the state of the art as discussed by the reference above, particularly with regards to the alleviation of the broad scope of disorders with one compound, the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Genentech, 108 F.3d at 1366 states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable." Therefore, methods of treating any symptom of any neurodegenerative disease by administering an effective amount of acetyl-leucine of the claims is not considered to be enabled by the instant specification.
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 double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., 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).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 36-43 and 50 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-18 of US 12,144,792. Although the conflicting claims are not identical, they are not patentably distinct from each other. The instant claims are drawn to a method of delaying onset of a 36. neurodegenerative disease that would otherwise be expected to manifest according to typical disease progression in a subject in need thereof comprising: treating one or more symptoms of the neurodegenerative disease by administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject. The patented claims are drawn to a method of treating a neurodegenerative disease or one or more symptoms associated with a neurodegenerative disease in a subject in need thereof comprising: administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject, wherein the neurodegenerative disease is chosen from Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple system atrophy type P (MSA-P), multiple system atrophy type C (MSA-C), frontotemporal dementia with parkinsonism, progressive supranuclear palsy, corticobasal degeneration, cerebellar downbeat nystagmus, Lewy Body dementia, and ataxia telangiectasia (Louis Barr disease), and wherein the therapeutically effective amount of acetyl-leucine or pharmaceutically acceptable salt thereof is administered at least two times a day to achieve a total daily dose of from about 500 mg to about 15 g. Thus, the instant claims are embraced and are therefore anticipated by the patented claims.
Claims 36-43 and 50 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of US 11,998,518. Although the conflicting claims are not identical, they are not patentably distinct from each other. The instant claims are drawn to a method of delaying onset of a 36. neurodegenerative disease that would otherwise be expected to manifest according to typical disease progression in a subject in need thereof comprising: treating one or more symptoms of the neurodegenerative disease by administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject. The patented claims are drawn to a method of treating a decrease in cognitive function associated with ageing in a subject in need thereof comprising: (a) identifying the subject having the decrease in cognitive function associated with ageing; (b) taking a baseline measurement of the subject’s cognitive function using one or more tests; (c) administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a treatment duration; (d) measuring the subject’s cognitive function using the one or more tests after the subject is treated; and (e) comparing the subject’s cognitive function after treatment to the baseline measurement to determine if there is an improvement in the subject's cognitive function.
The instant claims do not specifically recite steps a-e as claimed in the patent, however identifying the patient population in need of such treatment is considered customary to one of ordinary skill in the art. Furthermore, treating a decrease in cognition is considered to be a symptom of many of the diseases of the instant claims.
Thus, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time it was made.
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 36, 39, 41, and 43 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Strupp (Journal Neurology, 2013) of record.
Strupp teaches the use of acetyl-DL-leucine (Tanganil) for the treatment of cerebellar ataxia which is a neurodegenerative disease. Several assessments were employed to evaluate improvement in motor and quality of life parameters, namely Quality of life (EuroQol 5D-3L) and side effects. All evaluations demonstrated improvement in scores (abstract; page 2557, Design/Methods Section; Discussion).
Strupp teaches administering acetyl-DL-leucine in amounts of 5g/day (page 2557, Discussion).
Strupp teaches patients on medication with acetyl-DL-leucine showed a significant improvement of both the ataxic symptoms including gait, speech disturbance coordination, motor function (page 2557, Results and Discussion).
Based on the foregoing reasons, the instant claims are deemed anticipated over the cited art.
Claims 36, 39-41, and 43 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Schniepp (Cerebellum and Ataxias, 2016) of record.
Schniepp teaches acetyl-DL-leucine was observed to improve ataxic symptoms, including gait, in patients with sporadic and hereditary forms of ataxia.
Schniepp teaches patients were treated with acetyl-DL-leucine 5 g/d without titration (500 mg tablets of Tanganil™) for at least 4 weeks. Indication for the treatment with acetyl-DLleucine were the presence of cerebellar symptoms and abnormal findings in the domain “gait” of the Scale and Assessment of Ataxia (SARA) (page 1, Methods).
Schniepp teaches acetyl-DL-leucine may thus offer a new and complementary symptomatic treatment option for cerebellar gait disorders (page 2, Discussion).
Based on the foregoing reasons, the instant claims are deemed anticipated over the cited art.
Claim Rejections - 35 USC § 103
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 of this title, 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.
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 42 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Schniepp (Cerebellum and Ataxias, 2016) of record as applied to claims 36, 39-41, and 43 in the 102(a)(1) rejection above.
Schniepp is discussed above
Schniepp does not teach an enantiomeric excess of the L-enantiomer over the D-enantiomer or acetyl-L-leucine, as required by the instant claims.
It is well settled patent law that optical isomers would have been expected to possess different therapeutic activities. Most biological systems are sensitive to optical isomerism, motivating the skilled artisan to expect one or another optical isomer to effect greater, or lesser physiological activity. Absent some difference in kind between the various isomers, the skilled artisan would have seen each isomer as prima facie obvious. The skilled artisan would have expected optical isomers to be separable and isomers so separated to exhibit physiological effects at varying levels. Possessing a compound known to contain chiral centers, places all the resultant compounds in the skilled artisan's possession. Thus, use of one or another optical isomer by the skilled artisan would have seen as prima facie obvious, absent some difference in kind between the various isomers (see In re Adamson and Duffin, 125 USPQ 233 (CCPA 1960)).
Thus, based on the foregoing reasons, the instant claims are deemed unpatentable over the cited reference.
Claims 37-38, 42, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Strupp of record as applied to claims 36, 39, 41, and 43 in the 102(a)(1) in view of Gu (Health Qual Life Outcomes, 2011).
Strupp is discussed above.
Strupp teaches the use of acetyl-DL-leucine (Tanganil) for the treatment of cerebellar ataxia which is a neurodegenerative disease. Several assessments were employed to evaluate improvement in motor and quality of life parameters, namely Quality of life (EuroQol 5D-3L) and side effects. All evaluations demonstrated improvement in scores (abstract; page 2557, Design/Methods Section; Discussion).
Strupp teaches administering acetyl-DL-leucine in amounts of 5g/day (page 2557, Discussion).
Strupp teaches patients on medication with acetyl-DL-leucine showed a significant improvement of both the ataxic symptoms including gait, speech disturbance coordination, motor function (page 2557, Results and Discussion).
Strupp does not teach specifically teach wherein the symptom is reduced sleep quality.
Gu teaches quantifying the effect of insomnia on HRQoL is essential for targeting effective treatments, and comparing treatment cohorts in clinical practice (page 7, column 1, 3rd ¶).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have known that an improvement on the Quality of life (EuroQol 5D-3L) score as a result of acetyl-DL-leucine administration to patients with cerebellar ataxia, as taught by Strupp, would suggest that the symptom of sleep quality is also improved. The motivation, provided by Gu, teaches that the Quality of life survey is employed to quantify insomnia. Therefore, by demonstrating an improved score in said survey as disclosed by Strupp, the skilled artisan would expect, with a reasonable degree of success, that sleep quality and behavior are also improved, absent secondary considerations.
Strupp does not teach an enantiomeric excess of the L-enantiomer over the D-enantiomer or acetyl-L-leucine, as required by claims 42 and 50.
It is well settled patent law that optical isomers would have been expected to possess different therapeutic activities. Most biological systems are sensitive to optical isomerism, motivating the skilled artisan to expect one or another optical isomer to effect greater, or lesser physiological activity. Absent some difference in kind between the various isomers, the skilled artisan would have seen each isomer as prima facie obvious. The skilled artisan would have expected optical isomers to be separable and isomers so separated to exhibit physiological effects at varying levels. Possessing a compound known to contain chiral centers, places all the resultant compounds in the skilled artisan's possession. Thus, use of one or another optical isomer by the skilled artisan would have seen as prima facie obvious, absent some difference in kind between the various isomers (see In re Adamson and Duffin, 125 USPQ 233 (CCPA 1960)).
Based on the foregoing reasons, the instant claims are deemed unpatentable over the cited art.
Conclusion
Claims 36-43 and 50 are not allowed.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sahar Javanmard whose telephone number is (571)270-3280. The examiner can normally be reached on Monday-Friday, 9:00-5:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/SAHAR JAVANMARD/Primary Examiner, Art Unit 1622
Prosecution Insights