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 .
Maintained rejections
Rejections over Hinsby and Hibsby2 as set forth in the office action dated 3/6/26 are maintained. The text of the rejections of record is repeated below followed by reply to applicant’s remarks.
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.
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.
Claim(s) 94-103 and 105-119 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hinsby et al (US 2019/0111041; published 4/18/19).
In paragraph [0163] Hinsby teaches N-[2-hydroxy-3-{1-piperdinyl)-propoxy]-pyridine-1-oxide-3-carboxymidoyl chloride (arimoclomol), including its stereoisomers and acid addition salts. Hinsby teaches that arimoclomol can be used in a method of reducing risk in an individual of developing GBA-associated Parkinson’s disease wherein said individual is a patient with type I, II or III Gaucher’s disease.
Hinsdy’s teaching of administration of arimoclomol to a subject with Gaucher’s disease meets the limitation of current claims directed to treatment of Gaucher disease because the sole active step of the claims is practiced when arimoclomol (the claimed agent) is administered to a subject with Gaucher Disease (the claimed subject population).
Regarding therapeutically effective dose, route and frequency of administration:
Hinsby teaches that the therapeutically effective dose for a specific subject depends on various parameters including severity of the condition, weight and general state of the subject (paragraph [0181]). The recommended daily dose recited in paragraph [0181] encompasses all of the currently claimed doses. In paragraph [0183] art teaches various frequencies of administration including 1-3 times per day. Oral administration is described as a suitable route in paragraph [0186].
Regarding specific stereoisomers of arimoclomol, and specific acid addition salts:
In paragraph [0163] Hinsby teaches that stereo isomers and acid addition salts are within scope of agents that are suitable for administration to a subject with Gaucher disease. The (+)-R and (-)-S isomers as either citrate or maleate acid addition salts for use in the disclosed method are recited in paragraphs [0055] and [0176].
Regarding GBA activity, Hinsby teaches treatment of GBA-associated Parkinson’s disease with reduced GBA enzyme activity and/or levels (paragraph [0112].
Regarding limitations directed to signs of brain involvement:
Hinsby teaches treatment of GBA-associated Parkinson’s disease in a subject with reduced GBA enzyme activity. Since reduced GBA enzyme activity is a feature of Gaucher’s Disease, and Goucher’s disease is taught to be a contributing factor to GBA-associated Parkinson’s disease, it would have been obvious to treat GBA-associated Parkinson’s disease in a subject with Gaucher’s disease by administering to said subject an effective amount of arimoclomol. Examiner is interpreting GBA-associated Parkinson’s disease to meet the limitation directed to “with brain involvement”, “with clinical signs of brain involvement”, and “with at least 1 neurological symptom”.
Regarding subject not having been treated for Gaucher’s disease:
Hinsby does not recite whether subjects with Goucher’s disease to whom arimoclomol is administered have received prior treatment for Goucher’s disease. Examiner is interpreting this lack of teaching directed to prior treatment to imply that both treated and untreated groups are withint he scope of Hinsby’s disclosure. It would have been obvious to treat any subject with Gaucher’s disease by administering an effective amount of arimoclomol with an expectation that treatment will result in reduction of risk of developing GBA-associated Parkinson’s disease (paragraph [0163]).
Regarding subject’s age:
Gaucher’s disease is a genetic disorder which can affect subjects at very early age. It would have been obvious to administer arimoclomol to any subject with Gaucher’s disease with an expectation that treatment will result in reduction of risk of developing GBA-associated Parkinson’s disease.
The rejection above argues that it would have been obvious to treat and to reduce likelihood of GBA-associated Parkinson’s disease in a subject with Goucher’s disease. However, based on the disclosure of Hinsby, it would also be obvious to directly treat Gaucher’s disease in a subject in need of such treatment.
Interpretation of art’s disclosure with regards to treatment of Gaucher’s disease:
Hinsby teaches that they have discovered that arimoclomol increases GBA levels and increases GBA activity (paragraph [0010]). Hainsby also teaches that this activity in subjects presenting with Gaucher’s disease who have markedly reduced GBA activity and that arimoclomol increases GBA activity in subjects with Gaucher’s disease to clinically unaffected activity level. While the document as a whole focuses on treatment of other diseases that are associated with decreased GBA activity, paragraph [0010] clearly teaches that arimoclomol can restore GBA activity in patients presenting with Gaucher’s disease. In view of this teaching, it would have been obvious to administer arimoclomol to subjects presenting with Gaucher’s disease with an expectation that subject’s GBA activity will be restored to clinically unaffected levels.
Regarding limitations directed to treatment of symptoms of GD:
By treating GD it is inherent that an improvement in symptoms of GD is achieved.
Regarding new claim 119, directed to a method of decreasing chitotriosidase activity in a patient in need thereof. As applicants have demonstrated, reduction in chitotriosidase activity is achieved by performing the step of administrating arimoclomol to the subject. Since Hinsby teaches the step of administering arimoclomol to subject with GD, it is inherent that chitotriosidase activity in said subject is decreased. Subjects with GD represent a group that in need of reduction of chitotriosidase activity.
Same argument applies to the new limitation of 94 directed to “wherein the method decreases a chitotriosidase activity by at least 10%”. Since Hainsby teaches administration of the claimed active agent (arimoclomol) to the same subject population (subjects with GD), the claimed decrease in chitotriosidase activity is inherent.
Claim(s) 94-103 and 105-119 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hinsby et al (WO 2016/041561; published 3/24/2016; Hinsby2).
Hinsby2 teaches pharmaceutical formulations comprising arimoclomol including its stereoisomers and addiction salts. On page 1, lines 23-26 Hinsby teaches that oral doses from 50 to 800mg are well tolerated. On page 33, lines 9-14 art teaches the (+)-R and (-)-S stereoisomers of arimoclomol as citrate or maleate addition salts. Regarding administration and dosage art teaches that effective dose is to be determined based on disease and condition of the subject. Art also teaches administration one to three times a day (page 33, lines 17-28). Hinsby2 also teaches treatment of lysosomal storage disease by administering to a subject an effective amount of arimoclomol, and specifically teaches Gaucher disease types I, II, and III (page 39, lines 6-15).
A person of ordinary skill would have found it obvious to treat Gaucher’s disease types I, II or III in a subject in need by administering an effective dose of arimoclomol, it’s stereoisomer or/and citrate or maleate addition salt. It would have been obvious to determine the optimal amount and dosing schedule within the ranges taught by Hinsby. Since Hinsby teaches that 50-800mg of arimoclomol were well tolerated, it would have been obvious to determine effective dose within well tolerated range.
Regarding age, prior treatment and brain involvement, it would be obvious to treat any subject of any age who presents with Gaucher’s disease with an expectation that the disease and accompanying conditions would be improved. It would also be obvious to treat subjects who have not previously received treatment for Gaucher’s disease. A close inspection of the current specification does not reveal any special feature associated with lack of prior treatment. Any subject with Gaucher’s disease would be expected to benefit from administration of arimoclomol.
Regarding limitations directed to treatment of symptoms of GD:
By treating GD it is inherent that an improvement in symptoms of GD is achieved.
Regarding new claim 119, directed to a method of decreasing chitotriosidase activity in a patient in need thereof. As applicants have demonstrated, reduction in chitotriosidase activity is achieved by performing the step of administrating arimoclomol to the subject. Since Hinsby2 teaches the step of administering arimoclomol to subject with GD, it is inherent that chitotriosidase activity in said subject is decreased. Subjects with GD represent a group that in need of reduction of chitotriosidase activity.
Same argument applies to the limitation of claim 94 directed to “wherein the method decreases a chitotriosidase activity by at least 10%”. Since Hinsby2 teaches administration of the claimed active agent (arimoclomol) to the same subject population (subjects with GD), the claimed decrease in chitotriosidase activity is inherent.
Reply to applicant’s remarks
Remarks filed on 6/5/26 have been fully considered and found to be not persuasive in overcoming the rejection record.
With regards to rejection over Hinsby US 2019/0111041:
On page 8, applicants argue that at best Hinsby in paragraph [0010] teaches that administering arimoclomol to GD patients increases GBA levels (or activity) to clinically unaffected levels and therefore prevents development of GD pathologies. Applicants argue that Hinsby does not teach treatment of GD pathologies. This argument is not persuasive for 2 reasons.
Since applicants concede that Hinsby teaches a method of preventing GD pathologies, Examiner would like to point out that prevention of GD pathologies is within the scope of the claimed subject matter. Applicants define treatment to encompass prophylactic administration (See page 14, line 25; page 6, lines 1-2; page 6 lines 11-14).
The subject population of the current claims are subjects with GD. The subject population of Hinsby are also subjects with GD. The active agent in the current claims is arimoclomol. The active agent in Hinsby is also arimoclomol. Since Hinsby teaches administration of arimoclomol to subjects with GD, and the claims are also directed to administration of arimoclomol to subjects with GD, even if Hinsby did not recognize that the subject will benefit from reduction or prevention of symptoms of GD, the subject will inherently reap the claimed benefit.
On page 9 of the remarks, applicants argue that lowering chitotriosidase activity in subjects with GD is not an inherent feature in view of In Re Rijckaert. This argument is not persuasive. Applicant’s reliance on In Re Rijckaert is misplaced.
Rijckaert involved a patent application for a magnetic recording apparatus that established a precise mathematical relationship between time expansion/compression and three variables: α (the wrapping angle of tape around the drum), n (the number of head pairs), and M (non-recording intervals). This relationship—expressed as α*n/(180*(M+1))—allowed for optimal track filling on the magnetic tape. The approach was designed to allow reduction of acoustic noise by positioning heads close together with rigid mechanical coupling, while maintaining proper signal timing and track alignment regardless of drum wobble or other mechanical imperfections. The PTO rejected the application as obvious over two prior art references, despite neither reference teaching the claimed relationship or even discussing all three variables in combination. The fact pattern of the current rejection is different from that in Rijckaert. The rejection of record argues that since art administers the same agent to the same subject population, it is inherent that the resulting decrease in chitotriosidase activity occurs in both the claimed method and in the method of Hinsby. In Rijckaert the Office relied on combining two references in order to meet the claim limitations, meaning a person of ordinary skill in the art needed a teaching, suggestion, and motivation to combine the references. In current rejection there is no need for a teaching suggestion or motivation because art already teaches administration of arimoclomol to subjects with GD.
On page 9, third paragraph, Applicants argue that the GD and GBA associated diseases examined by Hinsby are caused by fundamentally different genotypes.
The rejection of record argues that it would be obvious to treat a subject with GD and GBA associated Parkinson’s disease with reduced GBA activity because Hinsby discloses this subject population. The subject population of Hinsby therefore includes individuals with reduced GBA activity. Examiner concedes that treatment of GD in subjects without GBA associated Parkinson’s would not be obvious over Hinsby1 as a sole reference. However, the subject population of the current claims is not limited to this group. Subjects with GD and GBA associated Parkinson’s is within the scope of the claimed subject matter.
With regards to Hinsby2, applicants present essentially the same argument. Hisnby2 teaches treatment of GD with arimoclomol, but fails to teach the relationship between arimoclomol and chitotriosidase activity. Examiner maintains that since reduction in chitotriosidase activity is derived from physiological activity of arimoclomol, the activity cannot be separated from the compound. Arimoclomol administered to a subject will inherently lower chitotriosidase activity because it is an inherent feature of arimoclomol.
Conclusion
Claims 94-103 and 105-119 are pending
Claims 94-103 and 105-119 are rejected
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628
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