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
Claims 1, 2, 10 and 19 are pending in the application. Claims 1, 2 and 10 are rejected. Claim 19 is withdrawn from further consideration.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 28th, 2026 has been entered.
Response to Amendment / Argument
Objections and rejections made in the previous Office Action have been overcome by Applicant's amendments to the claims. Therefore, arguments pertaining to these objections and rejections will not be addressed.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(1 of 2) Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Applicant has amended claim 1 to specifically recite that R1 can be -CH(COOH)OCH2-COOH where the point of attachment is at the CH carbon and that R4 can specifically be a phosphomethyl group. In the remarks filed January 28th, 2026, Applicant states that support can be found in paragraphs [0043], [0044] and [0051]. Paragraph [0043] discloses the following two structures:
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Paragraph [0044] discusses the compound succinyladenosine defined as (2S)-2-((9-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-6-yl)amino)succinic acid, which has the following structure:
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The specification contains broader disclosures in paragraphs [0041] and [0042]; however, neither of these paragraphs defines the corresponding positions fully as CH(COOH)OCH2-COOH and phosphomethyl. For instance, paragraph [0042] discloses the following structures:
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In the various disclosures above, certain stereocenters are defined whereas instant claim 1 defines no stereocenters in either absolute or relative configuration. The instantly claimed generic definition of claim 1 represents a hybrid of various embodiments where certain attributes are recited according to the structure of the species of [0043] but others remain generic. Furthermore, claim 1 recites that the various R-variables are chosen independently such that R1 can be -CH(COOH)OCH2-COOH but where R4 need not even be a phosphomethyl group according to the disclosure of paragraph [0043] and vice versa. Claims which change the scope relative to the originally filed claims may lack written description, see In re Ruschig, 371 F.2d 990, 154 USPQ 118 (CCPA) 1967) which supports that the original disclosure of a large genus did not support a later filed claim to a previously unnamed single species. Furthermore, Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1326, 56 USPQ2d 1481, 1486 (Fed. Cir.2000) notes that with respect to In re Ruschig, that “Ruschig makes clear that one cannot disclose a forest in the original application, and then later pick a tree out of the forest and say “here is my invention”. In order to satisfy the written description requirement, the blaze marks directing the skilled artisan to that tree must be in the originally filed disclosure.” In this situation, the disclosure points to a subgeneric embodiment where R1 and R4 are limited at the same time and where additional features (the stereocenters) are further limited. Instant claim 1 now specifically points to certain features of the embodiment while omitting others where the specification as filed contains no description of which features were considered critical and/or that could be varied while omitting others.
(2 of 2) Claim 1, 2 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claims 1 and 10 are independent and recite that the compositions comprise “a synthetic excipient including at least one of magnesium stearate, sodium carboxymethyl cellulose, or an ion exchange resin…”. Each of claims 1 and 10 further specifically recites limitations directed to injectable compositions. Claim 1 is directed to injectable pharmaceutical compositions in the alternative and claim 10 specifically recites an embodiment as being an injectable pharmaceutical composition. This combination of limitations is not adequately support by the original disclosure. The specification contains the following disclosure of carriers or excipients where the particular type of composition is not recited:
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The paragraph above mentions the three instantly recited components but not types of compositions. The specification discusses injectable compositions on page 18 as follows:
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None of the instantly recited magnesium stearate, sodium carboxymethyl cellulose, or an ion exchange resin are recited within injectable formulations. The specification discloses the use of magnesium stearate within solid dosage forms on page 18 as follows:
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The specification does not address which types of compositions should contain “sodium carboxymethyl cellulose or an ion exchange resin”. The specification on its own does not reasonably suggest injectable compositions comprising any of the three noted components at least since the specification (when discussing injectable formulations) teaches different excipients or carriers and (when discussing solid formulations) teaches application of magnesium stearate in formulations that would not necessarily be injectable. Furthermore, the prior art does not suggest or recognize the widespread injectability of all of these components. For instance, Hobbs et al. (Hobbs et al. Toxicology Reports 2017, 4, 554-559) teach the following on page 554:
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Hobbs et al. teach applications that are generally solids and not necessarily injectable. Similarly, ion exchange resins are solids. For these reasons, the originally filed disclosure combined with the knowledge in the art fails to reasonably suggest the now recited permutations where magnesium stearate, sodium carboxymethyl cellulose, or an ion exchange resin are found within injectable formulations.
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.
(1 of 2) Claim(s) 1 and 2 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by U.S. Patent No. 4,088,756 by Voorhees.
The prior art teaches capsules in column 8 as follows:
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The compositions are solid and contain adenosine, which is a compound of instant formula (I) where R1, R5 and R6 are -H, R2 and R3 are -OH and R4 is C1 hydrocarbyl (substituted C1 alkyl), where the composition includes magnesium stearate and further includes corn starch that can be considered an inert diluent (the instant specification defines starch as a type of inert diluent in paragraph [0057]). Regardless, magnesium stearate can also be considered to be doubly included as the synthetic excipient and inert diluent. The limitation of “synthetic” is considered a product-by-process limitation that does not distinguish from magnesium stearate obtained by non-synthetic methods.
Instant claim 1 further recites that the composition comprises a therapeutically effective amount “of about 1.0 to about 30 mg/kg body weight” but where the instant claims place no limitation on an object of administration, a dosing regimen or actual level of effectiveness that must be observed. The prior art teaches that the capsules contain 200 mg of adenosine, which would provide a dosage within about 1.0 to about 30 mg/kg for a mammal weighing, for instance, 70 kilograms.
The limitation of “pharmaceutical” is considered an intended use that does not structurally limit the claims.
(2 of 2) Claim(s) 1, 2 and 10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by JP 2010260833 A by Daicho (where a machine translation is appended to the reference and will be referred to herein) as evidenced by Martinussen et al. Nucleotide Metabolism, 2011, pages 91-107.
Daicho teaches compositions including the following:
[0026] Example 3 Tablets Curcumin 30 mg Cholic acid 150 mg Soy isoflavone 100 mg Green mussel powder 80 mg Inosinic acid 300 mg Heptadecanoic acid 90 mg Lactose 140 mg Magnesium stearate 6 mg Talc 3 mg Crystalline cellulose Appropriate total 1120 mg (1 tablet 280 mg 2 tablets 2 times a day) In addition, soy isoflavone glycosides were used instead of soy isoflavones to produce tablets.
The composition is a solid tablet and contains inosinic acid (discussed below), where the composition includes magnesium stearate and further includes lactose that can be considered an inert diluent (the instant specification defines lactose as a type of inert diluent in paragraph [0057]). Regardless, magnesium stearate can also be considered to be doubly included as the synthetic excipient and inert diluent. The limitation of “synthetic” is considered a product-by-process limitation that does not distinguish from magnesium stearate obtained by non-synthetic methods.
Claim 1 recites a composition comprising “a pharmaceutically acceptable ester, prodrug, or pharmaceutically acceptable salt” of a compound and claim 10 recites the composition comprising “a pharmaceutically acceptable ester, prodrug, or a pharmaceutically acceptable salt of adenylsuccinic acid or succinyladenosine”. The evidentiary reference by Martinussen et al. teaches on page 97: “IMP is the major branch-point in the formation of all purine nucleotides. In one branch, IMP is irreversibly converted into AMP in two enzymatic steps. First, succinyl-AMP (sAMP) is formed by condensation of aspartic acid and IMP catalyzed by adenylosuccinate synthase.” The specification states on page 13 that adenylosuccinate is an alternate name for adenylsuccinic acid. Accordingly, since IMP (also known as inosinic acid) converts to adenylsuccinic acid in vivo, IMP is considered a prodrug of adenylsuccinic acid. Adenylsuccinic acid is embraced by Formula I in claims 1 and 2 where R1 is and R4 are substituted hydrocarbyl, R2 and R3 are -OH and R5 and R6 are hydrogen.
The instant claims further recite that the compositions comprise a therapeutically effective amount “of about 1.0 to about 30 mg/kg body weight” but where the instant claims place no limitation on an object of administration, a dosing regimen or actual level of effectiveness that must be observed. The prior art teaches that the capsules contain 300 mg of inosinic acid, which would provide a dosage within about 1.0 to about 30 mg/kg for a mammal weighing, for instance, 70 kilograms.
The limitation “for promoting angiogenesis” in claim 10 is considered an intended use that does not structurally limit the claims. Similarly, the limitation of “pharmaceutical” is considered an intended use that does not structurally limit the claims.
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.
Claim(s) 1, 2 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent PGPub No. 2006/0286275 A1 by Salemme et al. in view of Hobbs et al. Toxicology Reports 2017, 4, 554-559 and as evidenced by Martinussen et al. Nucleotide Metabolism, 2011, pages 91-107.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Salemme et al. teach flavored seasoning compositions having the following components (abstract):
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As examples, Salemme et al. teach the following compositions on page 7:
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Formulation B contains IMP, which is defined in paragraph [0012] of the prior art as 5'-inosinic acid.
Claim 1 recites a composition comprising “a pharmaceutically acceptable ester, prodrug, or pharmaceutically acceptable salt” of a compound and claim 10 recites the composition comprising “a pharmaceutically acceptable ester, prodrug, or a pharmaceutically acceptable salt of adenylsuccinic acid or succinyladenosine”. The evidentiary reference by Martinussen et al. teaches on page 97: “IMP is the major branch-point in the formation of all purine nucleotides. In one branch, IMP is irreversibly converted into AMP in two enzymatic steps. First, succinyl-AMP (sAMP) is formed by condensation of aspartic acid and IMP catalyzed by adenylosuccinate synthase.” The specification states on page 13 that adenylosuccinate is an alternate name for adenylsuccinic acid. Accordingly, since IMP converts to adenylsuccinic acid in vivo, IMP is considered a prodrug of adenylsuccinic acid. Adenylsuccinic acid is embraced by Formula I in claims 1 and 2 where R1 is and R4 are substituted hydrocarbyl, R2 and R3 are -OH and R5 and R6 are hydrogen.
The instant claims further recite that the composition comprises a therapeutically effective amount “of about 1.0 to about 30 mg/kg body weight” but where the instant claims place no limitation on an object of administration, a dosing regimen or actual level of effectiveness that must be observed. The prior art teaches in paragraph [0087] that 8.6 grams of Formulation B was prepared such that ~2.5 mg of IMP would have been present, which would provide a dosage within about 1.0 to about 30 mg/kg for a mammal weighing a kilogram.
Regarding the solid dosage limitation of instant claim 1, the prior art teaches the presence of, for instance, dextrose, which is an inert diluent and citric acid, which is a buffering agent.
Regarding the language of claim 10, the preamble refers to “A pharmaceutical composition…” comprising components along with limitations “wherein as an injectable pharmaceutical composition, […] and as a solid dosage pharmaceutical composition” the composition further comprises additional options. These two embodiments, however, are not exhaustive to the scope of a “pharmaceutical composition” such that an oral dosage form would not be excluded and not limited according to the injectable or solid limitations. Regardless, the prior art teaches components as discussed above.
The limitation “for promoting angiogenesis” in claim 10 is considered an intended use that does not structurally limit the claims. Similarly, the limitation of “pharmaceutical” is considered an intended use that does not structurally limit the claims.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art compositions do not teach the presence of “a synthetic excipient including at least one of magnesium stearate, sodium carboxymethyl cellulose, or an ion exchange resin…”. The limitation of “synthetic” is considered a product-by-process limitation that does not affect the scope of the material(s) required.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
As found in the abstract, the prior art teaches the presence of flow agents. The prior art further discusses flow agents on page 5 as follows:
[0064] The seasoning mixture of the present invention may also contain flow agents. Flow agents help ingredients move smoothly from one location to another during manufacture. In addition, these agents act as anticaking agents reducing the hygroscopicity of the mixture and making the powder more resistant to exposure to humid environment. One or more flow agents may be used as part of the seasoning mixture. They may include, but are not limited to, silicon dioxide (e.g., Sylox 15TM), calcium stearate, glyceryl monostearate and glyceryl triacetate. A flow agent (e.g., silicon dioxide) may be present at a concentration up to about 2%, preferably about 1%, w/w of the flavored seasoning composition.
While Formulation B teaches the presence of Sylox 15TM, a person having ordinary skill in the art seeking to optimize the physical properties of the compositions would have at least been motivated to test known flow agents in analogous compositions. Hobbs et al. teach the following on page 554:
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Accordingly, a person having ordinary skill in the art would have been familiar with the properties of magnesium stearate as an anticaking agent. A person having ordinary skill in the art seeking to optimize the formulations of Salemme et al. would have been motivated to, for instance, test the analogous Formulation B where Sylox 15TM is replaced with magnesium stearate.
Conclusion
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626