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 . 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.
Priority
The instant application is a 371 of PCT/IL2022/050269 filed on 03/09/2022, which claims domestic benefit to US provisional application no. 63/296,032 filed on 01/03/2022 and US provisional application no. 63/159,236 filed on 03/10/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/20/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 09/19/2024 is acknowledged. Claims 3-4, 6-8, 13-14, 21, 24, 27, 38, and 40 are amended. Claims 11-12, 16-20, 22-23, 26, 29-37, 39, and 41-51 are cancelled.
Accordingly, claims 1-10, 13-15, 21, 24-25, 27-28, 38, and 40 are pending and being examined on the merits herein.
Specification
The disclosure is objected to because of the following informalities:
The chemical structures and texts in the synthesis steps shown on page 24 have poor resolution and legibility.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities:
The Chemical Formula 1 structure in claim 1 has poor resolution.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites “The levodopa amino acid complex …”
Claim 5 is an independent claim and does not have proper antecedence for “The levodopa amino acid complex”. It is suggested to change the “The” to “A”.
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.
Claim(s) 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CN110294789 (in IDS filed 09/20/2024, an English translation is provided in PTO-892 and used as the basis for this rejection).
CN’789 discloses method for synthesizing dopa-containing oligopeptides and their applications as prodrugs for Parkinson’s disease (first page under Description and also paragraph 0002).
CN’789 discloses the synthesis of several dopa dipeptide compounds in paragraph 0111 (page 15) in the original patent document and includes the following structure shown below:
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The compound shown above meets the limitation of Chemical Formula 3 of instant claim 1, wherein R11 and R12 are H, R14 is hydrogen, and R13 is a substituted alkyl.
Therefore, instant claim 1 is anticipated.
In regards to instant claims 2-4, the limitations recited here further limit the structure of Chemical Formula 1 in instant claim 1, but does not require that the recited levodopa amino acid complex must be Chemical Formula 1. Therefore, since instant claim 1 is anticipated by CN’789 for the alternative instant Chemical Formula 3, instant claims 2-4 are 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.
Claim(s) 1 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over CN110294789 (in IDS filed 09/20/2024, an English translation is provided in PTO-892 and used as the basis for this rejection).
The teachings of CN’789 are described above and teaches the levodopa complex recited in instant claim 1. Furthermore, CN’789 discloses their produced dopa-containing dipeptide has good stability and strong anti-degradation ability in liver homogenate, and is expected to be developed in a Parkinson’s disease treatment drug with high bioavailability and long-acting effect (paragraph 0187).
Even though CN’789 does not demonstrate the administration of their dopa dipeptides to treat a neurodegenerative disease, it would have been prima facie obvious before the effective filing date of the claimed invention to have administered the compound for the treatment of Parkinson’s as suggested in CN’789. One of ordinary skill in the art would have found it obvious to try with reasonable expectation of success because CN’789 discloses that their compounds are expected to be used for the treatment of Parkinson’s disease with high bioavailability and long-acting effect.
Claim(s) 6 is rejected under 35 U.S.C. 103 as being unpatentable over CN110294789 (in IDS filed 09/20/2024, an English translation is provided in PTO-892 and used as the basis for this rejection), as applied to claim 1 above, and further in view of US20160106765 (in PTO-892).
The teachings of CN’789 are described above and teaches the levodopa complex recited in instant claim 1.
CN’789, however, does not teach a liquid pharmaceutical composition comprising the levodopa amino acid complex.
US’765 discloses pharmaceutical compositions comprising a carbidopa prodrug and/or L-dopa prodrug that can be used in a method to treat Parkinson’s disease (Abstract). US’765 discloses that the pharmaceutical composition is a liquid composition (paragraphs 0254-0255).
It would have been prima facie obvious before the effective filing date of the claimed invention to formulate the L-dopa compounds of CN’789 into a liquid pharmaceutical composition as disclosed in US’765. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because both CN’789 and US’765 disclose L-dopa prodrugs for the treatment of Parkinson’s disease, and US’765 provides further guidance of formulating L-dopa prodrugs into liquid pharmaceutical compositions.
Claim(s) 5 is rejected under 35 U.S.C. 103 as being unpatentable over US4035507 (in IDS filed 09/20/2024) in view of Ichinose et al. (Journal of Neurochemistry, 1987 in IDS filed 09/20/2024).
US’507 discloses prodrug forms of L-dopa that are useful for the treatment of Parkinson’s disease (see Abstract).
US’507 lists several of their L-dopa prodrugs in columns 7-8 and includes diacetylated L-dopa conjugated to several prodrug moieties such as glycyl-3,4-diacetyloxy-L-phenylalanine shown below:
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The third compound from the top recited in instant claim 5 is shown below:
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Here, the compound of US’507 has the same diacetylated L-dopa structure but differs in the prodrug moiety that is being conjugated. The compound of instant claim 5 has a gamma-glutamyl moiety conjugated, whereas the compound of US’507 has a glycyl moiety conjugated.
Ichinose discloses the systemic administration of y-Glutamyl L-dopa (y-Glu-DOPA) to increase catecholamines such as dopamine, which may be applicable for the treatment of Parkinson’s disease (see Abstract). The structure of y-Glu-DOPA is shown below:
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Here, the compound shown above has the same gamma-glutamyl moiety as seen in the third compound of instant claim 5.
Ichinose discloses that y-Glu-DOPA is a known kidney-specific prodrug capable of increasing renal plasma flow, in which the y-Glu moiety is removed by y-glutamyl transpeptidase (y-GTP) and leaves free L-dopa which converts to dopamine (DA) (first paragraph left column page 928).
Ichinose discloses y-GTP may also have a physiological role in the brain, regulating the metabolism of exogenously supplied substrates such as L-DOPA, which are effective agents in the treatment of Parkinson’s disease (see right column page 928). Therefore, Ichinose suggest the use of y-Glu-DOPA to increase DA and noradrenaline (NA) in the brain mediated by y-GTP (see right column page 928 through first paragraph left column page 929).
As demonstrated in FIGS 2-3 (page 930) and FIG 4 (page 931), intraperitoneal injection of y-Glu-DOPA to mice increased DA markedly and NA moderately in the brain, and the increase of endogenous DA was followed by elevation of the main DA metabolites in a dose-dependent manner (see also Abstract).
Ichinose demonstrates in Table 1 (page 931) that DA levels in the plasma was higher after y-Glu-DOPA than after L-dopa.
Ichinose disclose that their results suggest the use of y-Glu-DOPA for the treatment of Parkinson’s disease by increasing the levels of catecholamines (see right column last paragraph page 931). Ichinose discloses that one additional advantage of y-Glu-DOPA as a possible drug for Parkinson’s disease may be that in addition to increasing DA, the NA content in the brain was also significantly increased, and that increased NA levels in the brain may be effective for some symptoms of Parkinson’s disease such as the difficulty in starting movements (see last paragraph left column page 932).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the glycyl-3,4-diacetyloxy-L-phenylalanine of US’507 by replacing the glycyl prodrug moiety with the gamma-glutamyl prodrug moiety as disclosed in Ichinose to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification because Ichinose demonstrates that conjugating the L-dopa with the gamma-glutamyl moiety resulted in increasing not only DA content but also NA content in the brain, which can be beneficial for the treatment of Parkinson’s disease. One of ordinary skill in the art would have a reasonable expectation of success because both US’507 and Ichinose teach L-dopa prodrugs that are conjugated to amino acid derived prodrug moieties for the treatment of Parkinson’s disease.
Claim(s) 9, 13, 21, 24-25, 27, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over CN110294789 (in IDS filed 09/20/2024, an English translation is provided in PTO-892 and used as the basis for this rejection) in view of US20160106765 (in PTO-892).
The teachings of CN’789 are described above. Furthermore, CN’789 discloses the synthesis of several dopa dipeptide compounds in paragraph 0111 (page 15) in the original patent document and includes the following structure shown below:
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The compound shown above is an enantiomer of the levodopa-tyrosine conjugate recited in instant claim 9.
CN’789, however, does not teach a liquid pharmaceutical composition comprising this compound and a stabilizer.
The teachings of US’765 are described above. Furthermore, US’765 discloses that their pharmaceutical compositions can include various excipients and provides several examples that include antioxidants, agents to adjust the pH and osmolarity, preservatives, thickening agents, colorants, buffering agents, bacteriostats, and stabilizers (paragraph 0243). US’765 disclose several antioxidants that are suitable for use in the pharmaceutical compositions (paragraph 0244). US’765 teaches that a given excipient is generally present in an amount of 0.3% to 10% by weight (paragraph 0243).
US’765 teaches that including carbidopa with L-dopa inhibits the peripheral metabolism of L-dopa to dopamine, which significantly reduces the L-dopa dose required for a therapeutically effective response and reduces the associated side effects (paragraph 0003).
US’765 teaches that their pharmaceutical compositions can have a pH of about 4.0 to 7.6 (paragraph 0259), and further demonstrates in Examples 12 that their L-dopa prodrugs had a good stability at pH of around 7 at room temperature over 1 and 7 days (paragraphs 0550-0552).
It would have been prima facie obvious before the effective filing date of the claimed invention to formulate the L-dopa compounds of CN’789 into a liquid pharmaceutical composition for the treatment of Parkinson’s disease as disclosed in US’765 and further include a stabilizer in an amount of 0.3% to 10% by weight as disclosed in US’765. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because both CN’789 and US’765 disclose L-dopa prodrugs for the treatment of Parkinson’s disease, and US’765 provides further guidance of formulating L-dopa prodrugs into liquid pharmaceutical compositions and further including various excipients such as stabilizers in an amount of 0.3% to 10% by weight into these compositions.
In regards to instant claim 21, it would have also been prima facie obvious before the effective filing date of the claimed invention to have adjusted the pH for the liquid pharmaceutical composition as taught by the combined teachings of CN’789 and US’765 described above to have a pH of around 7 at room temperature as disclosed in US’765. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because US’765 provides guidance of L-dopa prodrug formulations having a pH of around 7, which have good stability at room temperature over 1 and 7 days.
In regards to instant claims 24-25 and 27, it would have also been prima facie obvious before the effective filing date of the claimed invention to have to further included into the liquid pharmaceutical composition as taught by the combined teachings of CN’789 and US’765 described above the carbidopa and antioxidants as disclosed in US’765 to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to include carbidopa because US’765 discloses that including carbidopa with L-dopa inhibits the peripheral metabolism of L-dopa to dopamine, which significantly reduces the L-dopa. One of ordinary skill in the art would have a reasonable expectation of success because both CN’789 and US’765 the use of L-dopa prodrug compounds for treating Parkinon’s disease. Furthermore, one of ordinary skill in the art could have combined prior art elements of including antioxidants to the composition above according to known methods to yield predictable results because US’765 discloses including antioxidants and provides several antioxidants suitable for use in L-dopa prodrug pharmaceutical compositions.
Claim(s) 10, 14-15, 28, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over CN110294789 (in IDS filed 09/20/2024, an English translation is provided in PTO-892 and used as the basis for this rejection) in view of US20160106765 (in PTO-892), as applied to claims 9 and 27 above, and further in view of Yacoby-Zeevi et al. (US20140051755A1 in PTO-892).
The combined teachings of CN’789 and US’765 are described above and teach the composition recited in instant claims 9 and 27 as discussed above.
The combined references, however, do not disclose 10-45 % w/v of the recited levodopa-tyrosine compound as well as a stabilizer or antioxidant recited in instant claims 14-15 and 28.
Yacoby-Zeevi teaches methods of treating neurological or movement disorder in a patient by administering a pharmaceutically acceptable compositing comprising levodopa (Abstract).
Yacoby-Zeevi discloses the treated disorder is Parkinson’s disease (claim 34). Yacoby-Zeevi discloses that their compositions are liquid formulations (paragraph 0034). Yacoby-Zeevi discloses that their compositions comprise about 4-12% by weight levodopa (claim 3), about 10-35% by weight arginine (claim 9), and an agent that inhibits formation of oxidation products such as ascorbic acid (claims 10-11).
Yacoby-Zeevi discloses that their invention relates in part to the discovery that arginine can form a salt of carbidopa, and/or levodopa and/or entacapone, or tolcapone, that can be used to form a stable, liquid formulation that is suitable for various modes of administration (paragraph 0026).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the liquid pharmaceutical composition as taught by the combined teachings of CN’789 and US’765 described above to have about 4-12% by weight of the L-dopa compound as disclosed in Yacoby-Zeevi and further select arginine and ascorbic acid as disclosed in Yacoby-Zeevi as the stabilizer and antioxidant, respectively, to arrive at the claimed invention. One of ordinary skill in the art could have prepared the L-dopa amounts recited in the instant claims because Yacoby-Zeevi provides guidance of an overlapping range of 4-12% by weight L-dopa that is suitable for the treatment of Parkinson’s disease. See MPEP 2144.05 I. Furthermore, one of ordinary skill in the art could have combined prior art elements of using arginine and ascorbic acid in the composition according to known methods to yield predictable results because Yacoby-Zeevi provides guidance of including arginine to form stable liquid L-dopa formulations and including ascorbic acid as an antioxidant to inhibit formation of oxidation products in L-dopa compositions that are useful for the treatment of Parkinson’s disease.
In regards to instant claim 38, even though the combined teachings described above do not necessarily disclose the composition comprising less than about 5.0% w/v LD-Tyr-diketopeprazine after two weeks at 25 C, this component would flow naturally from the combined teachings described above because the instant specification discloses that levodopa-tyrosine conjugates are unstable and form impurities such as LD-Tyr-diketopeprazine over time (paragraph 0013 in instant specification), and further discloses that the addition of a recited stabilizer in liquid formulations comprising the levodopa-tyrosine conjugate helps to prevent this formation (paragraphs 00151-00152 pages 33-34).
Since the combined references described above teach a liquid formulation comprising overlapping amounts of levodopa-tyrosine conjugate and the same amounts of a recited stabilizer such as arginine, the less than 5.0% w/v LD-Tyr-diketopeprazine after two weeks at 25 C in the composition would flow naturally from following the suggestions of the prior art.
MPEP 2145 II recites “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
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 9, 13, 21, 24-25, 27, and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 32, 38, 42-43, 53, and 55 of copending Application No. 18/847,960 (‘960) in view of US20160106765 (in PTO-892).
Claim 1 of ‘960 recites a crystalline form of ((S)-2-amino-3-(3,4-dihydroxyphenyl) propanoyl)-L-tyrosine (Form N), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 20.1. The structure of the compound recited in ‘960 is shown below:
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Here, the ‘960 compound is identical to the levodopa-tyrosine compound recited in instant claim 9. Furthermore, claim 32 of ‘960 recites a pharmaceutical composition comprising the crystalline Form N of the ‘960 compound and a pharmaceutically acceptable excipient.
The claims of ‘960, however, do not recite a liquid pharmaceutical composition comprising this compound and a stabilizer.
The independent teaching of US’765 is described above. Furthermore, US’765 discloses that their L-dopa prodrug formulations can include various crystalline forms of L-dopa prodrugs for the treatment of Parkinson’s disease (paragraph 0390 and 0404).
It would have been prima facie obvious before the effective filing date of the claimed invention to formulate the compound recited in ‘960 into a liquid pharmaceutical composition as disclosed in US’765 and further include a stabilizer in an amount of 0.3% to 10% by weight as disclosed in US’765. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because both the claims of ‘960 and US’765 recite pharmaceutical compositions comprising crystalline L-dopa prodrug compounds and excipient, and US’765 provides further guidance of formulating crystalline L-dopa prodrugs into liquid pharmaceutical compositions for treating Parkinson’s disease and further including various excipients such as stabilizers in an amount of 0.3% to 10% by weight into these compositions.
In regards to instant claim 21, it would have also been prima facie obvious before the effective filing date of the claimed invention to have adjusted the pH for the liquid pharmaceutical composition as taught by the combination of the claims of ‘960 and US’765 described above to have a pH of around 7 at room temperature as disclosed in US’765. One of ordinary skill in the art could have combined prior art elements according to known methods to yield predictable results because US’765 provides guidance of L-dopa prodrug formulations having a pH of around 7, which have good stability at room temperature over 1 and 7 days.
In regards to instant claims 24-25 and 27, it would have also been prima facie obvious before the effective filing date of the claimed invention to have to further included into the liquid pharmaceutical composition as taught by the combination of the claims of ‘960 and US’765 described above the carbidopa and antioxidants as disclosed in US’765 to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to include carbidopa because US’765 discloses that including carbidopa with L-dopa inhibits the peripheral metabolism of L-dopa to dopamine, which significantly reduces the L-dopa. One of ordinary skill in the art would have a reasonable expectation of success because the claims of ‘960 recite a crystalline L-dopa prodrug compound, and US’765 discloses the use of L-dopa prodrug compounds for treating Parkinson’s disease. Furthermore, one of ordinary skill in the art could have combined prior art elements of including antioxidants to the composition above according to known methods to yield predictable results because US’765 discloses including antioxidants and provides several antioxidants suitable for use in L-dopa prodrug pharmaceutical compositions.
In regards to instant claim 40, it would have been prima facie obvious before the effective filing date of the claimed invention to have administered the liquid pharmaceutical composition as taught by the combination of the claims of ‘960 and US’765 described above for the treatment of Parkinson’s as disclosed in US’765. One of ordinary skill in the art would have found it obvious to try with reasonable expectation of success because both CN’789 and US’765 recite crystalline L-dopa prodrug compounds, and US’765 provides further guidance of using these compounds for the treatment of Parkinson’s disease.
This is a provisional nonstatutory double patenting rejection.
Claims 9-10, 14-15, 27-28, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 32, 38, 42-43, 53, and 55 of copending Application No. 18/847,960 (‘960) in view of US20160106765 (in PTO-892) and Yacoby-Zeevi et al. (US20140051755A1 in PTO-892).
The claims of ‘960 are as recited above.
The claims of ‘960, however, do not disclose 10-45 % w/v of the recited levodopa-tyrosine compound as well as a stabilizer or antioxidant recited in instant claims 14-15 and 28.
The independent teachings of US’765 and Yacoby-Zeevi are described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the liquid pharmaceutical composition as taught by the combination of the claims of ‘960 and US’765 described above to have about 4-12% by weight of the L-dopa compound as disclosed in Yacoby-Zeevi and further select arginine and ascorbic as disclosed in Yacoby-Zeevi as the stabilizer and antioxidant, respectively, to arrive at the claimed invention. One of ordinary skill in the art could have prepared the L-dopa amounts recited in the instant claims because Yacoby-Zeevi provides guidance of an overlapping range of 4-12% by weight L-dopa that is suitable for the treatment of Parkinson’s disease. See MPEP 2144.05 I. Furthermore, one of ordinary skill in the art could have combined prior art elements of using arginine and ascorbic acid in the composition according to known methods to yield predictable results because Yacoby-Zeevi provides guidance of including arginine to form stable liquid L-dopa formulations and including ascorbic acid as an antioxidant to inhibit formation of oxidation products in L-dopa compositions that are useful for the treatment of Parkinson’s disease.
In regards to instant claim 38, even though the combined references described above do not necessarily disclose the composition comprising less than about 5.0% w/v LD-Tyr-diketopeprazine after two weeks at 25 C, this component would flow naturally from the combined references described above because the instant specification discloses that levodopa-tyrosine conjugates are unstable and form impurities such as LD-Tyr-diketopeprazine over time (paragraph 0013 in instant specification), and further discloses that the addition of a recited stabilizer in liquid formulations comprising the levodopa-tyrosine conjugate helps to prevent this formation (paragraphs 00151-00152 pages 33-34).
Since the combined references described above recite a liquid formulation comprising overlapping amounts of levodopa-tyrosine conjugate and the same amounts of a recited stabilizer such as arginine, the less than 5.0% w/v LD-Tyr-diketopeprazine after two weeks at 25 C in the composition would flow naturally from following the suggestions of the combined references.
MPEP 2145 II recites “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is found allowable.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693