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 .
DETAILED ACTION
2. Claims 32 – 73 are pending in this application. Applicant’s preliminary amendment, filed August 4, 2022, is entered, wherein claims 32 – 73 are new and claims 1 – 31 are canceled.
Priority
3. This application is a national stage application of PCT/IL2021/050137, filed February 4, 2021, which claims benefit of domestic application 62/969,769, filed February 4, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
4. Applicant’s election without traverse of group I, claims 32 – 42, 46 – 56, and 60 – 70, drawn to a composition comprising (S)-2-amino-4-((1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-4-oxobutanoic acid (aspacytarabine) and at least one soluble stabilizer and/or solubilizer, filed November 12, 2025, is acknowledged. For the election of species, Applicant did not elected
(i) A specific composition recited in claims 36 – 37, 50 – 51, and 64 – 65.
in the reply filed on November 12, 2025.
Claims 43 – 45, 57 – 59, and 71 – 73 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected invention, there being no allowable generic or linking claim.
Claims 32 – 42, 46 – 56, and 60 – 70 are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/04/2022 and 11/12/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
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 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 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gengrinovitch (WO2017/093993A1).
a. Independent claim 32 is directed to a composition comprising (S)-2-amino-4-((1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-4-oxobutanoic acid (aspacytarabine) or pharmaceutically acceptable salt thereof and at least one soluble stabilizer and/or solubilizer. Dependent claims 33 – 35 are directed to the composition, wherein at one water soluble stabilizer and/or solubilizer is a linear polymer, wherein the water soluble linear polymer is non-ionic, wherein the water soluble linear polymer comprises polyethylene glycol. Dependent claim 40 is directed to the composition, wherein the composition is formulated as an oral composition. Dependent claim 41 is directed to the composition wherein the composition is formulated for injection in an aqueous media, wherein the aqueous media is at pH range of between 4 and 8. Dependent claim 42 is directed to the composition, wherein the aspacytarabine salt is a hydrochloride salt. Independent claim 46 is directed to a composition comprising (S)-2-amino-4-((1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-4-oxobutanoic acid (aspacytarabine) or pharmaceutically acceptable salt thereof and at least one soluble stabilizer and/or solubilizer, wherein the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution. Dependent claims 47 – 49 are directed to the composition, wherein at one water soluble stabilizer and/or solubilizer is a linear polymer, wherein the water soluble linear polymer is non-ionic, wherein the water soluble linear polymer comprises polyethylene glycol. Dependent claim 54 is directed to the composition, wherein the composition is formulated as an oral composition. Dependent claim 55 is directed to the composition wherein the composition is formulated for injection in an aqueous media, wherein the aqueous media is at pH range of between 4 and 8. Dependent claim 56 is directed to the composition, wherein the aspacytarabine salt is a hydrochloride salt. Independent claim 60 is directed to a composition comprising (S)-2-amino-4-((1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-4-oxobutanoic acid (aspacytarabine) or pharmaceutically acceptable salt thereof and at least one soluble stabilizer and/or solubilizer, wherein the concentration of the aspacytarabine within the composition in aqueous solution is between 20 – 1000 mg/mL. Dependent claims 61 – 63 are directed to the composition, wherein at one water soluble stabilizer and/or solubilizer is a linear polymer, wherein the water soluble linear polymer is non-ionic, wherein the water soluble linear polymer comprises polyethylene glycol. Dependent claim 68 is directed to the composition, wherein the composition is formulated as an oral composition. Dependent claim 69 is directed to the composition wherein the composition is formulated for injection in an aqueous media, wherein the aqueous media is at pH range of between 4 and 8. Dependent claim 70 is directed to the composition, wherein the aspacytarabine salt is a hydrochloride salt.
Gengrinovitch teaches an invention that provides prodrugs comprising cytarabine conjugated to a single amino acid, asparagine, for use in treating neoplastic diseases in medically compromised subjects (page 5, lines 3 – 6). According to one embodiment, the compound is Astarabine® (page 7, lines 4 – 5). Gengrinovitch teaches pharmaceutical compositions comprising at least one of the compounds and a pharmaceutically acceptable excipients (page 17, lines 24 – 26). In soft capsules, the active compound may be dissolved or suspended in polyethylene glycols. In addition, stabilizers may be added (page 20, lines 31 – 33). According to a certain embodiment, the formulation of Astarabine® for intravenous administration is an aqueous isotonic solution having osmolarity of about 300 mOsm and a pH of 4 – 8 (page 18, lines 3 – 5). The pharmaceutically acceptable salt is hydrochloride salt of astarabine (claim 26). In one example, the drug Astarabine® is supplied as a sterile lyophilized powder in glass ampoules of 1 g per ampoule. The drug is dissolved in 10 mL of sterile water for injection to obtain a final concentration of Astarabine® of 100 mg/mL.
Moreover, the instant specification discloses that aspacytarabine hydrochloride salt added to 3% of different stabilizers/solubilizers, such as Poloxamer 188, PEG, and PVP, at pH 5 are tested for solubility and stability following 24 hours in room temperature and confirms that the compositions comprising aspacytarabine and poloxamer, PEG, PVP, or combination thereof, provide stable solutions with a solubility of above 50 mg/mL (para. [0088-0089]). The disclosure “In soft capsules, the active compound may be dissolved or suspended in polyethylene glycols. In addition, stabilizers may be added” of Gengrinovitch meets all structural limitations “aspacytarabine” and “at least one water soluble stabilizer and/or solubilizer” of claim 46 and would achieve the same intended results, including “the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution”.
For the reasons above, Gengrinovitch anticipates the claimed invention.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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.
Claims 32 – 36, 38 – 42, 46 – 50, 52 – 56, 60 – 64, and 66 – 70 are rejected under 35 U.S.C. 103 as being unpatentable over Gengrinovitch (WO2017/093993A1) in view of Zhang (CN107137417A). Claims 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70 have been rejected here because they have been rejected by the primary reference under 102 above.
b. Regarding claims 32 – 36, 38 – 42, 46 – 50, 52 – 56, 60 – 64, and 66 – 70, Gengrinovitch teaches an invention that provides prodrugs comprising cytarabine conjugated to a single amino acid, asparagine, for use in treating neoplastic diseases in medically compromised subjects (page 5, lines 3 – 6). According to one embodiment, the compound is Astarabine® (page 7, lines 4 – 5). Gengrinovitch teaches pharmaceutical compositions comprising at least one of the compounds and a pharmaceutically acceptable excipients (page 17, lines 24 – 26). In soft capsules, the active compound may be dissolved or suspended in polyethylene glycols. In addition, stabilizers may be added (page 20, lines 31 – 33). According to a certain embodiment, the formulation of Astarabine® for intravenous administration is an aqueous isotonic solution having osmolarity of about 300 mOsm and a pH of 4 – 8 (page 18, lines 3 – 5). The pharmaceutically acceptable salt is hydrochloride salt of astarabine (claim 26). In one example, the drug Astarabine® is supplied as a sterile lyophilized powder in glass ampoules of 1 g per ampoule. The drug is dissolved in 10 mL of sterile water for injection to obtain a final concentration of Astarabine® of 100 mg/mL.
However, Gengrinovitch does not teach the composition comprising poloxamer. Gengrinovitch does not teach that the weight ratio between the aspacytarabine and the linear polymer is between 99:1 to 1:10, and the linear polymer has a weight percentage of between 0.1% and 30% w/w.
Zhang teaches pharmaceutical composition comprising cytarabine or its analog and ketorolac or its analog (Abstract). In one embodiment, the composition is parenteral solution with 20 parts by weight of cytarabine, 10 parts by weight of ketorolac tromethamine, 2 parts by weight of poloxamer, 15 parts by weight of isotonic regulator sodium chloride, and 50 parts by weight of water for injection (page 5, lines 32 – 34; page 6, line 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute polyethylene glycol as taught by Gengrinovitch with poloxamer in view of Zhang because Zhang teaches an exemplary composition comprising cytarabine and poloxamer and Zhang also teaches that the composition may comprise the analog of cytarabine. Since Zhang discloses that the composition may comprise an analog of cytarabine, it would have been obvious for one of ordinary skill in the art to consider applying Zhang’s example to a composition comprising aspacytarabine, which is an analog of cytarabine. One would have been motivated to substitute polyethylene glycol as taught by Gengrinovitch with poloxamer in view of Zhang because Zhang teaches an exemplary composition comprising cytarabine and poloxamer that is for parenteral use. A person of ordinary skill in the art would have expected that poloxamer may be substituted for PEG to achieve similar formulation goals. Based on the disclosure of Zhang, the weight ratio of cytarabine to poloxamer is 10:1 and the weight percentage of poloxamer is about 2.1 wt%. One would have performed routine experimentation to discover the best weight ratio and weight percentage of aspacytarabine and poloxamer for the optimal treatment characteristics. The disclosure of Gengrinovitch meets all structural limitations of claim 46 and would achieve the same intended results, including “the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution”. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success because Gengrinovitch teaches the claimed composition and Zhang provides example of composition comprising poloxamer and cytarabine as a guidance to achieve the composition with the specific linear polymer and its weight percentage.
Claims 37, 51, and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Gengrinovitch (WO2017/093993A1) in view of Zhang (CN107137417A) as applied to claims 32 – 36, 38 – 42, 46 – 50, 52 – 56, 60 – 64, and 66 – 70 above, and further in view of Carneiro et al. (International Journal of Molecular Sciences, 2019, Vol. 20, Issue 3, Reference included with PTO-892).
c. Regarding claims 27, 51, and 65, the references teach the limitations discussed above.
However, these references do not teach the composition comprising cyclodextrin.
Carneiro et al. disclose cyclodextrin-drug inclusion complexes (Title), whereas cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability (Abstract). Moreover, cyclodextrins are considered safe for parenteral administration and are commonly used with antitumor and immunomodulatory drugs. The FDA approves pharmaceutical formulations containing liposomal preparations of cytarabine, which have proven to be attractive and less toxic alternatives to the conventional drug formulations. Therefore, cyclodextrins are well tolerated, atoxic if used in safe concentration ranges and are considered safe for complexion with drugs (page 3, para. 2). Inclusion complexes formed with a host-guest molecule may exhibit improved chemical or biological properties compared to the host molecule alone. Such inclusion may improve aqueous solubility, dissolution, and bioavailability; increase the physiochemical stability of drugs and improve the shelf life of drugs; modify the drug delivery site and/or the time profile; reduce or eliminate unpleasant taste and smell; prevent drug-drug or drug-excipient interactions; and convert liquid drugs into microcrystalline or amorphous powders (page 3, para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute polyethylene glycol as taught by Gengrinovitch with cyclodextrin in view of Carneiro et al. because Carneiro et al. teach that cyclodextrin may form inclusion complexes with drug to achieve improved chemical or biological properties and Carneiro et al. indicate that cyclodextrins is known to be used with antitumor drugs. One would have been motivated to substitute polyethylene glycol as taught by Gengrinovitch with cyclodextrin in view of Carneiro et al. because of the improved properties when inclusion complexes are formed and cyclodextrins are known to be well tolerated and atoxic if used in safe concentration ranges and are considered safe for complexion with drugs. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to substitute polyethylene glycol as taught by Gengrinovitch with cyclodextrin in view of Carneiro et al. because Gengrinovitch teaches the claimed composition and Carneiro et al. teach the benefit of cyclodextrin-drug inclusion complexes and such substitution will yield predictable and improved drug formulation.
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 32 and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2 and 9 of U.S. Patent No. 8993278B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘278B2 anticipate the claimed invention.
a. Independent claim 32 is directed to a composition comprising (S)-2-amino-4-((1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-4-oxobutanoic acid (aspacytarabine) or pharmaceutically acceptable salt thereof and at least one soluble stabilizer and/or solubilizer. Independent claim 46 is directed to a composition comprising (S)-2-amino-4-((1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-4-oxobutanoic acid (aspacytarabine) or pharmaceutically acceptable salt thereof and at least one soluble stabilizer and/or solubilizer, wherein the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution.
‘278B2 teaches a pharmaceutical composition for human administration that includes an active ingredient consisting of a purified compound of the general formula (I):
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and a pharmaceutically acceptable carrier (claim 1). The pharmaceutical composition according to claim 1, wherein A is a side chain of aspartic acid and D is the residue of cytarabine (claims 2 and 9):
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The disclosure of ‘278B2 meets all structural limitations of claim 46 and would achieve the same intended results, including “the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution”.
For these reasons above, ‘278B2 anticipates the claimed invention.
Claims 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 10, and 13 of U.S. Patent No. 11058701B2 in view of Gengrinovitch (WO2017/093993A1).
b. Regarding claims 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70, ‘701B2 teaches a method for treating a neoplastic disease in a subject in need thereof, wherein the method comprises administering
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to the subject (claim 1). The compound is administered via continuous infusion (claims 3 and 10). The compound is administered as a pharmaceutical acceptable salt of hydrochloric acid (claims 5 and 13).
However, ‘701B2 does not teach the carrier is a linear polymer, wherein the linear polymer is non-ionic, wherein the linear polymer is polyethylene glycol. ‘701B2 does not teach the composition has a pH range of between 4 and 8 when in an aqueous media. ‘701B2 also does not teach the concentration of aspacytarabine.
Gengrinovitch teaches an invention that provides prodrugs comprising cytarabine conjugated to a single amino acid, asparagine, for use in treating neoplastic diseases in medically compromised subjects (page 5, lines 3 – 6). According to one embodiment, the compound is Astarabine® (page 7, lines 4 – 5). Gengrinovitch teaches pharmaceutical compositions comprising at least one of the compounds and a pharmaceutically acceptable excipients (page 17, lines 24 – 26). In soft capsules, the active compound may be dissolved or suspended in polyethylene glycols. In addition, stabilizers may be added (page 20, lines 31 – 33). According to a certain embodiment, the formulation of Astarabine® for intravenous administration is an aqueous isotonic solution having osmolarity of about 300 mOsm and a pH of 4 – 8 (page 18, lines 3 – 5). The pharmaceutically acceptable salt is hydrochloride salt of astarabine (claim 26). In one example, the drug Astarabine® is supplied as a sterile lyophilized powder in glass ampoules of 1 g per ampoule. The drug is dissolved in 10 mL of sterile water for injection to obtain a final concentration of Astarabine® of 100 mg/mL.
It would have been prima facie obvious for a person of ordinary skill in the art to combine the pharmaceutical composition used as taught by ‘701B2 with polyethylene glycol in view of Gengrinovitch because Gengrinovitch demonstrates that the combination of aspacytarabine and polyethylene glycol is used for treating neoplastic diseases. It would have been obvious to combine because both ‘701B2 and Gengrinovitch teach the composition of aspacytarabine for the use of neoplastic diseases. The disclosure of Gengrinovitch meets all structural limitations of claim 46 and would achieve the same intended results, including “the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution”. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the pharmaceutical composition used as taught by ‘701B2 with polyethylene glycol in view of Gengrinovitch because it is known in the art that the combination of aspacytarabine and polyethylene glycol is used for treating neoplastic diseases.
Claims 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 8 of U.S. Patent No. 11104698B2 in view of Gengrinovitch (WO2017/093993A1).
c. Regarding claims 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70, ‘698B2 teaches a pharmaceutically acceptable salt:
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wherein Y is pharmaceutically acceptable organic or inorganic acid or a residue thereof for treating cancer (claims 1 and 8). The salt may be (claims 2 – 5):
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‘698B2 teaches the pharmaceutical composition comprising the salt and a pharmaceutically acceptable excipient (claim 7). However, ‘698B2 does not teach the excipient is a linear polymer, wherein the linear polymer is non-ionic, wherein the linear polymer is polyethylene glycol. ‘698B2 does not teach the composition is formulated for infusion or injection which has a pH range of between 4 and 8 when in an aqueous media. ‘698B2 also does not teach the concentration of aspacytarabine.
Gengrinovitch teaches an invention that provides prodrugs comprising cytarabine conjugated to a single amino acid, asparagine, for use in treating neoplastic diseases in medically compromised subjects (page 5, lines 3 – 6). According to one embodiment, the compound is Astarabine® (page 7, lines 4 – 5). Gengrinovitch teaches pharmaceutical compositions comprising at least one of the compounds and a pharmaceutically acceptable excipients (page 17, lines 24 – 26). In soft capsules, the active compound may be dissolved or suspended in polyethylene glycols. In addition, stabilizers may be added (page 20, lines 31 – 33). According to a certain embodiment, the formulation of Astarabine® for intravenous administration is an aqueous isotonic solution having osmolarity of about 300 mOsm and a pH of 4 – 8 (page 18, lines 3 – 5). The pharmaceutically acceptable salt is hydrochloride salt of astarabine (claim 26). In one example, the drug Astarabine® is supplied as a sterile lyophilized powder in glass ampoules of 1 g per ampoule. The drug is dissolved in 10 mL of sterile water for injection to obtain a final concentration of Astarabine® of 100 mg/mL.
It would have been prima facie obvious for a person of ordinary skill in the art to combine the pharmaceutical composition used as taught by ‘698B2 with polyethylene glycol in view of Gengrinovitch because Gengrinovitch demonstrates that the combination of aspacytarabine and polyethylene glycol is used for treating cancer. It would have been obvious to combine because both ‘698B2 and Gengrinovitch teach the composition of aspacytarabine for the use of treating cancer. The disclosure of Gengrinovitch meets all structural limitations of claim 46 and would achieve the same intended results, including “the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution”. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the pharmaceutical composition used as taught by ‘698B2 with polyethylene glycol in view of Gengrinovitch because it is known in the art that the combination of aspacytarabine and polyethylene glycol is used for treating cancer.
Claims 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6 – 7, and 10 of U.S. Patent No. 12064445B2 in view of Gengrinovitch (WO2017/093993A1).
d. Regarding claims 32 – 35, 40 – 42, 46 – 49, 54 – 56, 60 – 63, and 68 – 70, ‘445B2 teaches a method for treating an acute myeloid leukemia in a subject in need thereof, wherein the method comprises administering
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to the subject (claim 1). The compound is administered as a pharmaceutical acceptable salt of hydrochloric acid (claims 6 – 7). The administration of the composition is parenteral, intravenous, or by intravenous infusion (claim 10).
However, ‘445B2 does not teach the carrier is a linear polymer, wherein the linear polymer is non-ionic, wherein the linear polymer is polyethylene glycol. ‘445B2 does not teach the composition has a pH range of between 4 and 8 when in an aqueous media. ‘445B2 also does not teach the concentration of aspacytarabine.
Gengrinovitch teaches an invention that provides prodrugs comprising cytarabine conjugated to a single amino acid, asparagine, for use in treating neoplastic diseases in medically compromised subjects (page 5, lines 3 – 6). According to one embodiment, the compound is Astarabine® (page 7, lines 4 – 5). Gengrinovitch teaches pharmaceutical compositions comprising at least one of the compounds and a pharmaceutically acceptable excipients (page 17, lines 24 – 26). In soft capsules, the active compound may be dissolved or suspended in polyethylene glycols. In addition, stabilizers may be added (page 20, lines 31 – 33). According to a certain embodiment, the formulation of Astarabine® for intravenous administration is an aqueous isotonic solution having osmolarity of about 300 mOsm and a pH of 4 – 8 (page 18, lines 3 – 5). The pharmaceutically acceptable salt is hydrochloride salt of astarabine (claim 26). In one example, the drug Astarabine® is supplied as a sterile lyophilized powder in glass ampoules of 1 g per ampoule. The drug is dissolved in 10 mL of sterile water for injection to obtain a final concentration of Astarabine® of 100 mg/mL.
It would have been prima facie obvious for a person of ordinary skill in the art to combine the pharmaceutical composition used as taught by ‘445B2 with polyethylene glycol in view of Gengrinovitch because Gengrinovitch demonstrates that the combination of aspacytarabine and polyethylene glycol is used for treating neoplastic diseases. It would have been obvious to combine because both ‘445B2 and Gengrinovitch teach the composition of aspacytarabine for the use of neoplastic diseases. The disclosure of Gengrinovitch meets all structural limitations of claim 46 and would achieve the same intended results, including “the composition is chemically and physically stable when stored at a temperature between -80 to 30 ⁰C for at least 1 month and for at least 24 hrs when formulated as an aqueous solution”. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine the pharmaceutical composition used as taught by ‘445B2 with polyethylene glycol in view of Gengrinovitch because it is known in the art that the combination of aspacytarabine and polyethylene glycol is used for treating neoplastic diseases.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOI YAN LEE whose telephone number is 571-270-0265. The examiner can normally be reached Monday - Thursday 7:30 - 17:30.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693