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 Claims
Claims 1-20, 22 and 29-37 are cancelled. Claims 21, 23-28 and 38-39 are pending and under examination.
Priority
This application is a continuation of 17/691,989 filed on 3/10/2022, which is a national stage entry of PCT/EP2021/082294 filed on 11/19/2021, which claims priority from US provisional applications 63/211,809 filed on 6/17/2021 and 63/115,749 filed on 11/19/2020 and European application EP20209467.8 filed on 11/24/2020.
Information Disclosure Statement
The information disclosure statements filed on 11/17/2025 and 12/17/2025 have been considered by the examiner.
Objections/Rejection Withdrawn
The objection over claim 22 is withdrawn per applicant’s amendment. However, it was noted that claim 22 was dependent on claim 21, which was amended to bring in the limitation of claim 22 while also deleting a limitation toward “methyl (Z)-N-(2-hydroxy-3-(piperidin-1-yl)nicotinamide 1-oxide”. Deleting this limitation now allows for compositions without “methyl (Z)-N-(2-hydroxy-3-(piperidin-1-yl)nicotinamide 1-oxide” and additionally note that applicant’s claim 22, which was indicated as having allowable matter if imported into the independent claim, also had an amount for the “methyl (Z)-N-(2-hydroxy-3-(piperidin-1-yl)nicotinamide 1-oxide, or a pharmaceutically salt thereof” of 0.05% to about 0.1%. After applicant’s amendment, this limitation as was formerly recited in claim 22 is no longer present in the claims. The examiner must consider claim 21 in regards to this deletion amendment as all claims dependent on former claim 21 were considered with having all the limitations of former claim 21.
The rejections of claims 21 and 29 and claims 22-28 and 30-37 are withdrawn per applicant’s amendment to claim 21 in regards to the rejection and cancellation of claims 29-37.
As these objections and rejections are withdrawn, applicant’s arguments are now moot.
Rejections Maintained – Modified As Necessitated by Amendment
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 28 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 28 allows for “about 47 mg” while claim 27, on which claim 28 depends, has the lower endpoint of the range at “about 50 mg”. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Applicant could make the endpoint of the ranges in claim 27 to be “about 47 mg to about 500 mg”.
Response to Applicant’s Arguments for the Rejection under USC 112(d)
Applicant argues that the use of “about” in claim 27 would encompass “47 mg” in claim 28, which depends on claim 27. However, the issue is that claim 28 recites “about 47 mg” so under the same definition of “about” with +/- 10%, “about 50 mg” would allow down to 45 mg and “about 47 mg” would allow down to “42.3 mg”, which is below 45 mg. Therefore, “about 47 mg” in claim 28 extends the range that is presented in claim 27, on which it depends. Applicant may either make the range in claim 27 “about 47 mg to about 500 mg” or amend claim 28 to delete the recitation of “about” from before “about 47 mg” so that it is only “47 mg”.
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, 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.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Urogdi US 20040006232.
Urogdi teaches (R)-(+)-N-[2-hydroxy-3(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl Chloride Citrate (synonym for N-{[2-hydroxy-3-piperidin-1-ylpropyl oxy } pyridine-3-carboximidoyl chloride 1-oxide citrate that is produced and dried to make a 98% pure product (paragraphs 61-62). The abstract provides for optically active enantiomers (R)-(−)-N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboxamidine and (S)-(+)-N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboxamidine (abstract). Urogdi teaches optically active enantiomer that is preferably at least 96% (paragraph 7). Urogdi’s teachings envision the pure form. Urogdi recognizes making the drug in high purity and high yield (paragraph 5). In figures 1-5 of Urogdi, the same reactants and intermediates are provided. Thus, as the reaction is similar, there is an expectation of similar by-products present after the reaction as these are by-products of such a reaction (see MPEP 2112). Urogdi teaches 98% of product obtained as dry precipitate (powder) (example 5). Example 5 provides for preparation of (R)-(+)-N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl Chloride (paragraphs 48-59) with a 98/2 enantiomer ratio (paragraph 58) in the preparation of “(R)-(+)-N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride maleate” (paragraph 54). Thus, the 98 in the ratio refers to the R enantiomer that is being prepared and the 2 refers to the S enantiomer which is recognized by Urogdi to be the other enantiomer.
Claim 21 does not dictate amounts for the other compounds besides arimoclomol present in the composition, and thus, may be present at any amount.
Urogdi does not provide kit or unit dosage form.
However, Urogdi does provide for powders of the pharmaceutical which can be construed as a dosage form and since Urogdi provides for such a form, this may constitute the kit product.
Thus, one of ordinary skill in the art before the time of filing would have utilized the teachings of Urogdi to make (R)-(+)-N-[2-hydroxy-3(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl Chloride Citrate by similar reactants/intermediates and provide the composition with impurities listed to make as a unit dosage form and provide in a kit for use. Urogdi recognizes having at least 96% and obtaining 98% product while also obtaining ratio of R enantiomer that is in a 98:2 enantiomer ratio when discussing the arimoclomol and the preparation of the R enantiomer. There is a reasonable expectation of success in increasing the purity of the (R)-(+)-N-[2-hydroxy-3(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl Chloride or its citrate salt with teachings of Urogdi to provide for higher purity forms of this R enantiomer form of the compound with Urogdi also recognizing the presence of the (S) enantiomer as the other enantiomer based on 98:2 enantiomer ratio when preparing the R enantiomer. The teachings of Urogdi motivate obtaining higher purity of arimoclomol and also provides for preparation of the R enantiomer in a high ratio which would motivate one of ordinary skill in the art to continue to purify the R enantiomer to 98% or higher and reducing the amount of the S enantiomer at values of 2% or less of the total of the purified compound. In regards for instructions for use or prescription (a type of instruction for use), this is generally not considered for patentability as it is a written material that are not related to the chemical(s) themselves. “Additionally, where the printed matter and product do not depend upon each other, no functional relationship exists. For example, 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. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.” (MPEP 2111.05 I B).
Claims 23-28, 38 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Urogdi US 20040006232 and Hinsby US 20170239232.
Urogdi teaches limitations as discussed above. Urogdi teaches (R)-(+)-N-[2-hydroxy-3(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl Chloride Citrate (synonym for N-{[2-hydroxy-3-piperidin-1-ylpropyl oxy } pyridine-3-carboximidoyl chloride 1-oxide citrate that is produced and dried to make a 98% pure product (paragraphs 61-62). Urogdi teaches optically active enantiomer that is preferably at least 96% (paragraph 7). Urogdi’s teachings envision the pure form. Urogdi recognizes making the drug in high purity and high yield (paragraph 5).
Urogdi does not teach the amounts/concentrations of drug in the composition, the addition of an excipient and/or carrier, and treating Niemann Pick disease, Type C by administering the arimoclomol orally or otherwise. Urogdi does not provide for kits, but this was explained in the rejection under USC 103 over Urogdi. Note that Hinsby below provides for arimoclomol formulations for use in treatment of patients.
Hinsby teaches a pharmaceutical formulation which provides for extended release of an active pharmaceutical ingredient selected from N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride, its stereoisomers and the acid addition salts thereof (abstract). Hinsby teaches tablets with active agent and excipients and the option of carrier (paragraphs 50 and 56-59). Hinsby teaches amounts of API including 50 and 100 mg, 50 to 60 mg, 60 to 70 mg and 70 to 80 mg (paragraphs 249-250). Hinsby also teaches 100-150 mg, 300 mg-400 mg and 400-500 mg (paragraph 252). Hinsby teaches 5 to 40% w/w of the drug (paragraph 168). Hinsby teaches treating lysosomal storage disorders like Niemann Pick disease, Type C (paragraph 278). Hinsby teaches oral dosage forms (paragraphs 125 and 129). Hinsby provides the administration of the dosage form by oral dosage and/or bolus IV injection. Thus, it does envision instructing users as well as multiple dosage forms.
One of ordinary skill in the art at the time of instant filing would have utilized the high purity arimoclomol citrate of Urogdi in formulations and methods of Hinsby, which use this drug, to obtain a formulation with high purity arimoclomol citrate and to better and more safely treat patients with Niemann Pick, Type C. Both references are to arimoclomol and its salts like the citrate form. There is a reasonable expectation of success in combining the references to produce the compositions and methods of the instant claims. In regards for instructions for use or prescription (a type of instruction for use), this is generally not considered for patentability as it is a written material that are not related to the chemical(s) themselves. “Additionally, where the printed matter and product do not depend upon each other, no functional relationship exists. For example, 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. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.” (MPEP 2111.05 I B).
Response to Applicant’s Arguments over the Rejections under USC 103
Applicant argues that Urogdi does not provide for a composition with the amount of the S enantiomer as in applicant’s claims 21 and 38. In this rejection under USC 103, the prior art only needs to motivate purifying of the desired enantiomer, which Urogdi does exemplify preparations of the R enantiomer of arimoclomol while also teachings the making of its citrate salt form. Urogdi also provides for overlapping percentages and close enantiomer ratios in its teachings (MPEP 2144.05 regarding obviousness of ranges). Additionally, applicant should consider MPEP 2144.04 VII – purifying of an old product – “Pure materials are novel vis-à-vis less pure or impure materials because there is a difference between pure and impure materials. Therefore, the issue is whether claims to a pure material are nonobvious over the prior art. In re Bergstrom, 427 F.2d 1394, 166 USPQ 256 (CCPA 1970).” Furthermore, applicant should note Spectrum Pharmas. V. Sandoz Inc., 15-1407 (Oct. 2, 2015) (Lourie, J.) where a purified enantiomer form of a compound was held obvious over prior art that taught the compound and also a 50:50 enantiomer mixture.
Hinsby was used to teach that N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride (arimoclomol), its stereoisomers and the acid addition salts thereof, which is the same pharmaceutical active compound as in Urogdi, can be used in dosage forms at claimed amounts as well as its recognized purpose to treat lysosomal storage diseases like Niemann Pick disease.
Additionally, the entire limitation that was formerly recited in claim 22, no longer exists in the claims and was not fully imported into claim 21.
Non-Statutory 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 double patenting rejection is appropriate where the conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21, 23-28 and 38-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11707456. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘456 provide for the formulation with all components of the claims. ‘456 does not provide for the kit or instructions or prescription. In regards for instructions for use or prescription (a type of instruction for use), this is generally not considered for patentability as it is a written material that are not related to the chemical(s) themselves. “Additionally, where the printed matter and product do not depend upon each other, no functional relationship exists. For example, 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. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.” (MPEP 2111.05 I B). ‘456 provides for the pharmaceutical and chemical components of a composition, and thus, will satisfy the component of the kit.
Claims 21, 23-28, and 38-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 158 and 174-175 of copending 18/037,461. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘461 provides for a kit with the claimed drug, components, and claimed amounts. ‘461 does not provide for the other components of claim 21, but these would result from the process of making as in claims of ‘461 with similar reactants. ‘461 provides a method of making arimoclomol that would result in the enantiomer amounts/ratios of the claims. Claim 174 of ‘461 provides for greater than 98% a stereoisomeric quantity of greater than 98% N-{[(2R)-2-hydroxy-3-piperidin-1- ylpropyl]oxy}pyridine-3-carboximidoy chloride 1-oxide. ‘461 does not provide for the kit or instructions or prescription. In regards for instructions for use or prescription (a type of instruction for use), this is generally not considered for patentability as it is a written material that are not related to the chemical(s) themselves. “Additionally, where the printed matter and product do not depend upon each other, no functional relationship exists. For example, 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. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.” (MPEP 2111.05 I B).
This is a provisional double patenting rejection as the claims have not yet been issued.
Response to Applicant’s Arguments
Applicant asks the non-statutory type double patenting rejections to be held in abeyance. As applicant is not arguing or filing terminal disclaimers, these rejections are maintained.
Although claim 22 was not rejected in the non-statutory double patenting rejection over copending 18/037,461, the change in scope to delete “methyl (Z)-N-(2-hydroxy-3-(piperidin-1-yl)nicotinamide 1-oxide” requires further consideration of the claim without carrying this limitation. Former claim 22 contained all the limitations of former claim 21.
The claims of ‘461 were amended by applicant to cancel its claims 160-173 and add new claims 174-175.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613
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