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 1-30 are pending in the application. Claims 1-15 are rejected. Claim 13 is objected to. Claims 16-30 are withdrawn.
Restriction/Election of Species
Applicant’s election without traverse of Group I, claims 1-15, in the reply filed on April 10, 2026 is acknowledged.
Claims 16-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 10, 2026.
Priority
This application is labeled as a divisional of U.S. Application No. 18/635,765, filed on April 15, 2024, which is a continuation of U.S. Application No. 17/686,538, filed on March 4, 2022, which claims benefit of Provisional Application No. 63/156,533, filed on March 4, 2021.
Information Disclosure Statement
The Information Disclosure Statement(s) (IDS) filed on September 26, 2025, December 3, 2025 are April 10, 2026 are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the Examiner has considered the IDS documents and signed copies of the 1449 forms are attached.
Claim Objections
Claim 13 is objected to because of the following informalities:
Claim 13 should be amended to replace “the soluble glyburide formulation” with -the stabilized and soluble glyburide formulation- for sake of consistency.
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.
Claims 8, 10, 12 and 13 are 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 8 recites “the formulation” and is rejected as indefinite. It is unclear whether Applicant intended “the formulation” to refer to a) “the stabilized and soluble formulation,” b) “the diluted formulation,” or c) both a) and b). Applicant should amend claim 8 to clearly indicate what “the formulation” is in reference to. For the purposes of examination, “the formulation” as recited in claim 8 is being interpreted as being drawn to option a) “the stabilized and soluble formulation” as recited in parent claim 1.
Claim 10 recites “combining the sugar alcohol and the glyburide...in a weight ratio of 27 to 40:1” and is rejected as indefinite. It is unclear whether Applicant intended the recited weight ratio to pertain to a) sugar alcohol to glyburide or b) glyburide to sugar alcohol.
Similarly, claim 12 recites “combining the base and the glyburide...in at a molar ratio of 27 to 40:1” and is rejected as indefinite. It is unclear whether Applicant intended the recited weight ratio to pertain to a) base to glyburide or b) glyburide to base.
Claim 13 recites “the soluble glyburide formulation further comprises” followed by seven chemical structures. It is unclear whether Applicant intended the stabilized and soluble glyburide formulation to comprise a) a single compound as recited in claim 13 or a combination of compounds or b) each of the compounds recited in claim 13. It is suggested Applicant amend the claim to include the word “or” before the last recited chemical structure. For the purposes of examination, claim 13 is being interpreted as being drawn to further comprising only one additional compound in the stabilized and soluble glyburide formulation.
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.
Claims 1-6, 9-12 and 15 are rejected under 35 U.S.C. § 103 as being unpatentable over Zhong et al. (U.S. PGPub. No. 2020/0022993 A1; January 23, 2020) in view of Figueroa-Valverde et al. (Biomedical Papers, 2012, 156:122-127).
Determining the scope and contents of the prior art (See MPEP § 2141.01)
Zhong et al. teach “a pharmaceutical composition comprising a sulfonylurea drug, a cyclodextrin and an additive.” See e.g., paragraph [0005]. Zhong et al. further teach that “preferably, the sulfonyl urea drug is glibenclamide” (i.e., “Formula 1, also referred to as Glyburide) in e.g., paragraphs [0003] and [0016]:
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Zhong et al. further teach “the additive is selected from [inter alia] tris(hydroxylmethyl)aminomethane (i.e., Tris or Tris base). See e.g., paragraph [0023]. It is noted that Tris buffer has a buffering capacity range of pH 7.0 to 9.0 and a pKa of 8.08 at 25°C. See e.g., paragraph [00120] of the instant specification. Zhong et al. further teach “preferably, the additive is sodium hydroxide.” See e.g., paragraph [0028]. Zhong et al. further teach the pharmaceutical composition further comprises a lyophilization additive e.g., “mannitol.” See e.g., paragraphs [0030] and [0118]. In addition, Zhong et al. teach that “in addition to the above active agents and additives, other excipients, buffering agents or pH regulator...may also be comprised in the composition.” See e.g., paragraph [0076]. Zhong et al. further teach the pharmaceutical composition has a pH of preferably 6-10 and also adjusting the solution formulation to pH 8.0. See e.g., paragraphs [0047], [0103] and [0104]. In addition, Zhong et al. teach a method for preparing the prior art pharmaceutical composition, wherein the method comprises combining the sulfonylurea drug with a solution (e.g., wherein solvent is physiological saline) comprising the additive and the cyclodextrin followed by addition of the lyophilization additive to eventually form a freeze-dried product. See e.g., paragraphs [0048]-[0053]. Moreover, Zhong et al. teach the prior art pharmaceutical composition “may be dissolved in physiological saline to produce an injection” or otherwise “diluted by 500 times with 0.9% solution of sodium chloride.” See e.g., paragraphs [0079] and [0153]. Zhong et al. also teach a 1:1-50 “weight ratio of the sulfonylurea drug to the additive” which encompasses the required weight ratio limitation of instant claim 10 (i.e., wherein the additive is, for instance, the disclosed lyophilization additive mannitol). See e.g., paragraphs [0011] and [0030]. Lastly, Zhong et al. teach the following with respect to therapeutic treatments (see paragraph 0054):
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Note that the expression “for reducing an infusion rate of a glyburide formulation diluted in a saline infusion solution over the course of a 24 hour infusion,” as recited in the preamble of instant claim 1, is drawn towards characteristics that would necessarily be present from employing the instantly claimed method and is, therefore, considered to be non-limiting. In addition, note that instant claim 1 is directed to product-by-process limitations nested within a method claim. However, the nesting of a product-by-process limitation within a method claim does not change the proper construction of the product-by-process limitation itself. MPEP 2113 states the following:
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
"[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith." In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972). Office personnel should note that reliance on the alternative grounds of 35 U.S.C. 102 or 35 U.S.C. 103 does not eliminate the need to explain both the anticipation and obviousness aspects of the rejections.
In this situation, the product-by-process limitations are drawn towards “a stabilized and soluble glyburide formulation” and “a diluted formulation.” Additionally, note that the expression “wherein the stabilized and soluble formulation has a pH outside of the buffering capacity of the buffering agent” is drawn towards characteristics that would necessarily be present in the claimed “stabilized and soluble glyburide formulation” and is, therefore, considered to be non-limiting. Notwithstanding, however, Zhong et al. teach an injectable composition of glibenclamide (i.e., glyburide) in physiological saline, wherein the pH did not change by more than 0.2 pH units over the course of 24 hours. See e.g., paragraph [0127] and Table 3. For example, Table 3 shows a starting pH value of 5.90 and a pH value of 5.72 after a period of 24 hours for a glyburide composition in saline. In addition, the expression “wherein the diluted formulation is configured to be infused into a human at a rate of less than 16 mL/hour for 24 hours” is also considered to be non-limiting due to being drawn towards characteristics necessarily present in the “diluted formulation” product obtained as a result of employing the instantly claimed method. Similarly, the expression “wherein the pH of the diluted formulation does not change by more than 0.2 pH units over the course of the 24 hour infusion,” as recited in instant claim 3, is also drawn towards characteristics that would necessarily be present in the “diluted formulation” of parent claim 1 and is, therefore, considered to be non-limiting. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). In addition, “[p]roducts of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP § 2112.01(II).
Ascertainment of the differences between the prior art and the claims (See MPEP § 2141.02)
Regarding instant claims 7 and 8, although Zhong et al. teach tris(hydroxylmethyl)aminomethane (i.e., Tris base) as an additive, Zhong et al. does not explicitly teach a combination of Tris-HCl (i.e., acid addition salt) and Tris base having the instantly claimed weight ratio of 7:4 or 6.2:5.0. However, Zhong et al. does teach pharmaceutical compositions further comprising “a pH regulator (e.g., hydrochloric acid).” See e.g., paragraphs [0030], [0032] and [0104].
Regarding instant claim 12, Zhong et al. does not teach a molar ratio between a base and glyburide. Zhong et al. does, however, teach a 1:1-10 “weight ratio of the sulfonylurea drug to the additive” (i.e., wherein the additive is, for instance, sodium hydroxide). See e.g., paragraphs [0011] and [0028].
Regarding instant claim 13, Zhong et al. does not teach that the pharmaceutical composition further comprises one of the chemical compounds recited in the claim. However, Figueroa-Valverde et al., in the same field of endeavor, teach glibenclamide-OH [i.e., a glyburide/glibenclamide derivative originally referenced in Asian J Chem 2011, 23(9):3999-4002; see e.g., page 4000] having the chemical structure below and which corresponds to the second compound as recited in instant claim 13 (see e.g., page 123):
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Regarding instant claim 14, Zhong et al. does not teach the instantly claimed 26 to 34 mg/mL concentration of sugar alcohol. However, Zhong et al. teach a pharmaceutical composition comprising 5 g of mannitol in 100 mL solution (i.e., 50 mg/mL concentration). See e.g., paragraph [0118].
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claims 7 and 8, considering that Zhong et al. teach both Tris base as an additive and the addition of hydrochloric acid, it would have been obvious to a person of ordinary skill in the art to arrive at the instantly claimed Tris-HCl/Tris combination. It is within the ability of a skilled artisan to determine the appropriate buffer formulation (e.g., Tris, Tris-HCl, Tris/Tris-HCl, etc.) for a given experimental workflow or application. Tris buffer has a buffering capacity range of pH 7.0 to 9.0 and a pKa of 8.08 at 25°C and is, therefore, generally known to be effective at maintaining a physiological pH range. Therefore, a skilled artisan looking to further improve properties such as stability, solubility, bioavailability, etc., would be motivated to determine the appropriate weight ratio of Tris base and its acid addition salt (e.g., Tris-HCl) through a process of routine optimization. Furthermore, the skilled artisan would have a reasonable expectation that the resulting Tris-HCl/Tris buffer would not alter the utility of the pharmaceutical composition taught by Zhong et al- especially in view of the fact that Zhong et al. provide support for formulations comprising both Tris and HCl. See e.g., paragraphs [0023], [0030], [0032] and [0104]. “It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.” In re Williams, 36 F.2d 436, 438 (CCPA 1929).
Regarding instant claim 13, it would, therefore, have been obvious to further comprise glibenclamide-OH, as taught by Figueroa-Valverde et al., in the pharmaceutical composition of Zhong et al. Figueroa-Valverde et al. teach glibenclamide-OH as having the same utility (and hypoglycemic effect) as glyburide. Therefore, one skilled in the art would have had a reasonable expectation that a combination of compounds known individually to treat diabetes mellitus would be effective in treating diabetes mellitus collectively. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose. In re Kerkhoven, 205 USPQ 1069 (CCPA 1980). The idea of combining them flows logically from their having been individually taught in the prior art. At least in the interest of determining various combinations that may result in greater treatment efficacy, a skilled artisan would have been motivated to include an additional active ingredient in the prior art composition with a reasonable expectation of success in treating, for instance, diabetes mellitus.
Regarding instant claims 12 and 14, it would have been obvious for a person of ordinary skill in the art to arrive at the instantly claimed molar ratio (recited in instant claim 12) and concentration range (recited in instant claim 14) based on the teaching of Zhong et al. The optimization of result-effective variables, i.e., variables that achieve a recognized result, such as concentration, are considered to be within the ability of the skilled artisan. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, a skilled artisan would be motivated to optimize the molar ratio/concentration range taught by Zhong et al. as part of the routine optimization process.
Conclusion
No claims are allowed.
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/D.M.S./Examiner, Art Unit 1626
/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626
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