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
This application is a U.S. national stage patent application under 35 U.S.C. § 371 of International Application No. PCT/IL2020/050960, filed on September 3, 2020, which application claims the benefit of and priority to U.S. Provisional Patent Application Nos. 62/896,518, filed on September 5, 2019, and 62/897,648, filed on September 9, 2019
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 25, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-4, 6, 8-12, 14-16 and 20-23 are currently pending.
Applicant’s election without traverse of Group I, claims 1-4, 8-12 and 14-16, in the reply filed on July 25, 2025 is acknowledged. Applicant further elected without traverse, the following species (a) L-Dopa-Tyr, (b) carbidopa, (c) arginine, and (d) a mixture of N-acetyl cysteine and ascorbic acid. Claims 1-4, 6, 8-12 and 14-16 read on the elected species.
Claims 1-4, 6, 8-12, and 14-16 are currently active and subject to examination.
Claims 20-23 are withdrawn.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.”
Claims 1-4 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hoffmann-La Roche & Co (GB 1364505 A) (of record, cited in the Restriction/ Election requirement dated Jan. 28, 2025) (Herein “Roche”).
Claim 1 is directed towards a liquid composition comprising a levodopa amino acid (LDAA) conjugate of formula (I):
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. The Applicant elected L-Dopa-Tyr as the LDAA conjugate for examination.
Roche teaches liquid pharmaceutical formulations comprising LDAA conjugates such as L-Dopa-Tyr for the treatment of Parkinson’s disease:
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Roche, Specification, p. 8; Roche, Specification, p. 13.
Therefore, claim 1 is anticipated.
Claims 2-4 read on the structural features of L-Dopa-Tyr and are therefore also anticipated.
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(s) 1-4, 6, 8-12, and 14-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hoffmann-La Roche & Co (GB 1364505 A), as applied to claims 1-4 above, and further in view of Yacoby-Zeevi et al. (US20170296491A1).
The rejection of claims 1-4 under 35 U.S.C. 102 as anticipated by Roche is incorporated herein by reference. As such these claims were prima facie obvious at the time of filing.
Claim 6 is directed towards the liquid composition of claim 1, comprising between about 10 and 45% w/v of the LDAA conjugate.
As shown above, Roche teaches that the active ingredient can comprise 1 to 99% by weight (Roche, Specification, p. 8, lines 40-45).
While Roche does not specifically teach about 10 to about 45% w/v of the LDAA conjugate, one of ordinary skill in the art would have a reasonable expectation of success to use about 10 to about 45% w/v of the LDAA conjugate because similar solutions are commonly known in the art.
For example, Yacoby-Zeevi is directed towards liquid pharmaceutical compositions comprising a levodopa amide (LDA) compound,
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(Yacoby-Zeevi, Specification, paragraph 9), similar to the instantly claimed LDAA conjugates, in combination with carbidopa, wherein the concentration of the levodopa compound is 12% or 20% w/v:
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Yacoby-Zeevi, Specification, p. 12.
Therefore, claim 6 was prima facie obvious at the time of filing.
Claim 8 is directed towards the liquid pharmaceutical composition of claim 1, further comprising a decarboxylase inhibitor. Claim 9 specifies that the decarboxylase inhibitor is carbidopa.
While Roche does not teach to formulate the LDAA conjugate in combination with carbidopa (CD), one of ordinary skill in the art would have a reasonable expectation of success to formulate the LDAA conjugate in combination with carbidopa because liquid formulations comprising levodopa analogs and carbidopa are known in the art and it is commonly known in the art to administer L-Dopa or its analogs in combination with carbidopa for enhanced therapeutic efficacy.
For example, Yacoby-Zeevi teaches that “[t]he co-administration of LD and a peripheral DOPA decarboxylase (aromatic L-amino acid decarboxylase) inhibitor such as carbidopa or benserazide has been found to reduce the dosage requirements of LD and, respectively, some of the side effects.” (Yacoby-Zeevi, Specification, paragraph 5). Yacoby-Zeevi further teaches liquid formulations comprising a levodopa amide compound and carbidopa, as shown above in the rejection of claim 6 (Yacoby-Zeevi, Specification, paragraphs 125-127).
Therefore, claims 8-9 were prima facie obvious at the time of filing.
Claim 10 is directed towards the liquid composition of claim 1, further comprising a base. Claim 11 specifies that the base is selected from arginine, TRIS, NaOH and any combination thereof. Claim 12 specifies that the composition comprises between 0.1% to about 30% w/v of the base.
As shown above, Roche teaches that the pharmaceutical formulation can comprise conventional pharmaceutical additives such as stabilizing agents or buffers (Roche, Specification, p. 8, lines 30-37). While Roche does not teach that the liquid composition further comprises a base such as arginine at a concentration between about 0.1% to about 30% w/v one of ordinary skill in the art would have a reasonable expectation of success to include arginine at a concentration between about 0.1% to about 30% w/v because similar levodopa compositions are known in the art.
For example, Yacoby-Zeevi teaches liquid compositions comprising LDA and CD in combination with 0.9% to 3.70% arginine (Yacoby-Zeevi, Specification, p. 12, paragraph 127, Table 8).
Therefore, claims 10-12 were prima facie obvious at the time of filing.
Claim 14 is directed towards the liquid composition of claim 1, further comprising an antioxidant. Claim 15 specifies that the antioxidant is selected from ascorbic acid or a salt thereof, a cysteine, a bisulfite or a salt thereof, glutathione, a tyrosinase inhibitor, a Cu2+ chelator, and any combination thereof. Claim 16 specifies that the concentration of the antioxidant is between about 0.05 to about 2.0% w/v.
As shown above, Roche teaches that the pharmaceutical formulation can comprise conventional pharmaceutical additives such as stabilizing agents or buffers (Roche, Specification, p. 8, lines 30-37). While Roche does not teach that the stabilizing agent is an antioxidant such as ascorbic acid and a cysteine at a concentration of between about 0.05 to about 2.0% w/v, one of ordinary skill in the art would have a reasonable expectation of success to include about 0.05 to about 2.0% w/v of ascorbic acid and cysteine because similar levodopa compositions are known in the art.
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For example, Yacoby-Zeevi teaches that the antioxidant ascorbic acid and n-acetyl cysteine (NAC) can be included in the formulation at concentrations from about 0.01% to about 1% by weight:
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Yacoby-Zeevi, Specification, p. 10; Yacoby-Zeevi, Specification, p. 5.
Therefore, claims 14-16 were prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Nonstatutory 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 1-4, 6, 8-12, and 14-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-10, 13-15, 21, 24-25, 27-28 and 38 of copending Application No.18/549,452.
Claim 1 is directed towards a liquid composition comprising a levodopa amino acid (LDAA) conjugate of formula (I):
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. The Applicant elected L-Dopa-Tyr as the LDAA conjugate for examination.
Claim 9 of copending Application No.18/549,452 is directed towards a liquid composition comprising L-Dopa-Tyr:
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(copending claim 9).
Claims 2-4 read on the L-Dopa-Tyr compound. As such, claims 1-4 are provisionally rejected on the grounds of non-statutory double patenting as both the instant claims and claim 9 of the copending application are directed towards a liquid composition comprising L-Dopa-Tyr.
Dependent claims 6, 8-12, and 14-15 further specify the concentration of the LDAA conjugate (claim 6), the additional therapeutic agent, carbidopa (claims 8-9), the base (e.g. arginine) and its concentration (claims 10-12), and the antioxidant or combination of antioxidants (e.g. ascorbic acid and a cysteine) (claims 14-15). Copending claim 10 is directed towards the same concentration (10-45% w/v) of LD-Tyr. Copending claims 13-15 are directed towards the same stablilizer/base (arginine, Tris, NaOH) in the same concentration (0.1 to 30% w/v). Copending claims 24-25 additionally specify that the composition comprises a decarboxylase inhibitor that is carbidopa. Copending claims 27-28 are directed towards the same antioxidant or combination of antioxidants (ascorbic acid and cysteine).
Therefore, claims 1-4, 6, 8-12, and 14-15 are provisionally rejected on the ground of nonstatutory double patenting over copending claims 10, 13-15, 24-25 and 27-28.
Claims 1-4, 6, 8-12, and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-10, 13-15, 21, 24-25, 27-28 and 38 of copending Application No. 18/549,452, as applied to claims 1-4, 6-8, 8-12 and 14-15 above, and further in view of Yacoby-Zeevi et al. (US20170296491A1).
Claim 16 is directed towards the liquid pharmaceutical formulation of claim 14, wherein the antioxidant is present in a concentration from about 0.05% to about 2.0%. As shown in the rejection of claims 14-15 above, the copending Application no. 18/549,452 also claims that the liquid pharmaceutical composition comprises an antioxidant.
While the copending application does not claim a specific concentration of antioxidant, one of ordinary skill in the art would have a reasonable expectation of success to include about 0.05 to about 2.0% of antioxidant because this concentration is commonly known in the art for similar compositions. For example, see the teachings of Yacoby-Zeevi in the 35 U.S.C. 103 rejection above (Yacoby-Zeevi, Specification, p. 10, paragraphs 120-121; Yacoby-Zeevi, Specification, p. 5, paragraphs 65-67).
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629