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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. CN 202311045174.5, filed on 08/17/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/06/2023 complies with the
provisions of 37 CFR 1.97, 1.98, and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered on the merits. See attached copies of PTO-1449.
Status of the claims
The claims filed on 07/06/2026 accordingly with Applicant’s response to the non-final office action mailed on 03/18/2026 are entered onto the record. Claims 2-10 and 12-22 are pending. Claims 12 and 13 are currently withdrawn. Claims 1 and 11 were canceled. Claims 2-10 and 14-22 are currently examined.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action mailed on 07/06/2026:
The rejection of claim 6 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendments,
The rejection of claim 6 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendments,
The rejection of claim 11 under 35 U.S.C. 112(d) is withdrawn in view of Applicant’s amendments,
Response to Arguments
Applicant's arguments filed 07/06/2026 have been fully considered but they are not persuasive. The rejections under 35 U.S.C. 103 are all maintained.
Applicant argues:
“Gizurarson does not disclose the claimed combination and the Examiner’s assembly of components constitutes impermissible hindsight. Gizurarson's overarching objective is clearly stated: rapid systemic absorption. The reference describes formulations designed to maximize the rate at which nimodipine enters the bloodstream while minimizing nasal residence time.”
This argument is not found persuasive.
As discussed in the prior non-final office action mailed 03/18/2026, Gizurarson teach a composition comprising (1) nimodipine, (2) diethylene glycol monoethyl ether, (3) ethyl oleate, and (4) phospholid lecithin, which read on the compositions of the presently amended independent claim 2. Further, as previously discussed in the same non-final action, where a claim is drawn to a composition and an intended use of the composition, if the prior art structure is capable of performing the intended use, then it meets the limit of the claim (see MPEP §2111.02 II). Therefore, whether the instant application or Gizurarson disclose intended uses of the composition, the instant claims to a composition where the intended use does not result in a structural difference between the claimed invention and the prior art.
Additionally, Gizurarson does not disclose an intention to “[minimize] nasal residence time”. Rather, Gizurarson teaches that the inventions disclosed therein are optimized for nasal administration and the inventions are intended to take advantage of preferable characteristics of the nasal mucosal biology. For example, Gizurarson teach “the lower viscosity formulations, when converted into droplets, for example, by a nasal sprayer during intranasal delivery, produce a spray pattern optimized for delivering the therapeutic agent to the mucosal membrane.” (see para. [0022]).
Applicant Further argues “A person of ordinary skill in the art, seeking to achieve the systemic absorption taught by Gizurarson, would be positively discouraged from adopting a formulation strategy designed to retain the drug in the nasal mucosa and brain tissue for sustained local or CNS delivery.”
This argument is not found persuasive.
However, Gizurarson also teach “the alkoxy-group also increases the bioadhesion of the
composition to the site of administration on the mucosal surf ace thereby prolonging the
duration of the composition at the site of administration. This can increase the amount of
therapeutic agent that is ultimately absorbed” (see para. [0022]). One of skill in the art of neurotherapeutics and methods of drug delivery, would understand and be motivated to optimize nasal delivery formulations to prolong duration at administration site and enhance penetration through the nasal mucosa whether intending to enhance delivery to brain or systemically.
Applicant argues “Zuo is directed to phospholipid complexes for improving drug stability and lipid solubility - a technology domain entirely unrelated to nasal delivery or brain targeting. Zuo does not mention Transcutol P, does not describe nasal formulations, does not address nose-to-brain delivery, and does not provide any data on brain drug concentrations.”This argument is not found persuasive.
Gizurarson disclose “In order to penetrate the mucus, the vehicle should be biocompatible with mucus and hence have a certain degree of hydrophilicity. However, the vehicle should preferably also possess lipophilic properties to dissolve a clinically relevant
amount of the therapeutic agent of interest.” One of skill in the art of neurotherapeutics and methods of drug delivery, would understand and be motivated to optimize nasal delivery formulations suitable for nasal mucosa administration and be motivated to rely on teachings of drug stability, lipid solubility (e.g., lipophilic properties disclosed by Gizurarson) including those of Zuo to reach a suitable formulation.
As discussed above, Gizurarson teach diethylene glycol monoethyl ether (i.e., Transcutol P). As discussed in the prior non-final office action mailed 03/18/2026, Gizurarson also teach amounts of diethylene glycol monoethyl ether. Zuo is relied upon for teaching the specific species of lecithin recited by instant claim 6.
Applicant argues “The Amendments Eliminate the "Genus Combination" Basis for Rejection” This argument is not found persuasive.
As discussed above Gizurarson teach the combination of the presently amended instant claim 2.
Applicant argues that the instant specification “provides objective evidence supporting the non-obviousness of the claimed invention” Specifically, Applicant argues (A) that “[t]he high DTP values constitute unexpected results that weigh strongly in favor of nonobviousness”, (B) “the claimed formulation produces a drug reservoir effect and sustained drug accumulation in the brain”, and (C) “specification reports permeability coefficients”.
This argument is not found persuasive.
The instantly claimed invention is directed towards a composition, and, while the instant specification does provide data regarding drug levels in the brain, these results are considered properties inherent to the composition and not structural limitations. Gizurarson teaches the same compositions and demonstrates systemic levels after nasal administration. Gizurarson is silent on brain concentrations, however, the lack of disclosure of brain concentration levels does not preclude the conclusion that compositions of Gizurarson achieve brain penetration after nasal administration. One of skill would understand the teachings of Gizurarson to optimize compositions and formulations that use the beneficial biology of nasal administration to achieve desired concentrations in the brain. Furthermore, where the prior art teaches compositions that read on the instantly claimed invention properties of those compositions are considered necessarily present. See MPEP§ 2112.01 (II).
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:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2-10, 14-22 are rejected under 35 U.S.C. 103 as being unpatentable over Gizurarson et al., (WO 2008/089426 A2, published July 24, 2008) and in further view of Zuo et al., (WO 2022/068585 A1, published 07/04/2022).
Regarding claims 2, 5, 14-17, and 19-20, Gizurarson et al., teaches pharmaceutical compositions comprising:
(1) one or more therapeutic agents (see pg. 11, para. [0037- pg. 12, para. [0040], including anti-hypertensive agents (see pg. 11, line 14), such as nimodipine (see pg. 12, line 26);
(2) “additional compounds that enhance the solubility of the therapeutic agent” including,
(2a) “other solubilizers” (see pg. 20, lines 22-23), including diethylene glycol monoethyl ether (i.e., the solvent of the instantly claimed invention) (see pg. 20, lines 24-25);
(2b) esters, including ethyl oleate (i.e., the diluent of the instantly claimed invention) (see pg. 20, lines 19-20); and
(3) absorption promoters, including the phospholid lecithin (see pg. 19, lines 9-11).
Regarding claims 3, 4, 9, 10, 18, and 21, Gizurarson et al., teach that the therapeutic agent (e.g., nimodipine) can comprise “about 0.001% (w/v)[weight by volume] to about 20% (w/v) of the composition (see pg. 8, lines 10-12). Gizurarson et al. further teaches the solubilizer diethylene glycol monoethyl ether (i.e., the solvent of the instantly claimed invention) can be “present in an amount of from about 0.1% (w/v) to about 50% (w/v)” (see pg. 20, lines 30-31). The amount of nimodipine required by instant claim 3 is 4-50 parts by weight, which can overlap with the range of amounts taught by Gizurarson et al. The amount the solvent required by instant claim 3 is 5-300 parts by weight, which can overlap with the range of amounts taught by Gizurarson et al. For example, a composition based on the teachings of Gizurarson et al. may comprise 4mg nimodipine and 20mg of diethylene glycol monoethyl ether out of 100mL volume (i.e., 4% w/v and 20% w/v, respectively) which reads on 4 parts by weight and 20 parts by weight, respectively, of the instantly claimed invention.
Therefore, it would be prima facia obvious to one of skill in the art at the time of filing of the instant application to make a composition comprising an amount of nimodipine and diethylene glycol monoethyl ether according to the teachings of Gizurarson et al. that read on the claimed range of the instant application where the ranges overlap and where there is no showing of criticality of the higher end point of the instantly claimed range. See MPEP 2144.05 (I) and In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941).
However, Gizurarson et al. is silent with respect to the concentrations (e.g., the parts by weight) of the diluent (i.e., ethyl oleate), and absorption enhancer (i.e., lecithin).
MPEP 2144.05 (II) states “differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” and, the instant application fails to provide evidence that the claimed 500-900 and 700-850 parts by weight of diluent and 20-200, 40-160, and 60-120 parts by weight of absorption enhancer required by claim 3 are critical.
See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382, “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) “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.”
Thus, based on the teachings of Gizurarson et al., it would be prima facia obvious to one of skill in the art at the time of filing of the instant application to make a composition comprising amounts of a diluent and an absorption enhancer that read on the claimed weight ratios of the instant application.
Regarding claim 6, as discussed above, Gizurarson et al. teach compositions which comprise lecithin but is silent on the specific lecithin agents recited in the instant claim 6. However, Zuo et al., (WO 2022/068585 A1, published 07/04/2022) is directed to pharmaceutical phospholipid complexes for improved stability and fat solubility of medicines and discloses the use of phospholipid egg yolk lecithin E80 (see paras. [0009] –[0011] and Examples 1-3). Zuo et al. further discloses the substitution of lecithin E80 with egg yolk lecithin PL-100M (see para. [0095] and Example 4).
Where a single prior art reference discloses a genus encompassing the claimed species or subgenus but does not expressly disclose the particular claimed species or subgenus, an additional prior art reference can be used to show the differences between the primary reference and the claimed invention is obvious (see MPEP § 2144.08). Therefore, the use of lecithin E80 and lecithin PL100M of instant claim 6 are obvious based on the of the compositions comprising lecithin as taught by Gizurarson et al. and in further view of the use of lecithin E80 and lecithin PL100M in pharmaceutical compositions as taught by Zuo et al.
Regarding claims 7 and 8, compositions based on the teachings of Gizurarson et al. “may also include a sweetener or flavoring agent” (see pg. 21, para. [0052]). For example, the composition may include an aromatic or aromatic elixir, or lemon oil, orange oil, cherry juice, raspberry juice, citric acid syrup, wild cherry syrup, or combinations thereof. Based on the teachings of Gizurarson et al., it would be prima facia obvious to one of skill in the art to substitute one fruit flavoring agent additive (i.e., grape essence) for anther flavoring agent additive (e.g., the aromatics, elixirs, oils, juices, or syrups disclosed in Gizurarson et al.) of a different fruit (e.g., orange, lemon, cherry, raspberry) for the same purpose (i.e., adding an aroma or a fruit flavor to the composition) with a reasonable expectation of success (see MPEP § 2144.06 II). Therefore, the compositions taught by Gizurarson et al. read on instant claims 7-8.
Regarding claim 22, which depends from claim 2, recites that the formulation of claim 2, “has a permeation coefficient of not less than 2 × 10-7 cm/s as measured by Franz diffusion cell using procine nasal mucosa” which introduces a property (i.e., permeation coefficient) of the composition when measured using a particular method (i.e., Franz diffusion cell). MPEP 2122.01 states “Products 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. Id.” Therefore, formulations taught by Gizurarson that read on the instantly claimed invention are expected to have the same properties (i.e., a permeation coefficient as recited in claim 22 when measured by a Franz cell).
Conclusion
Claims 2-10 and 14-22 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALAN JEROME FOWLER whose telephone number is (571)272-0195. The examiner can normally be reached Monday - Friday 9-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALAN J FOWLER/ Examiner, Art Unit 1691
/RENEE CLAYTOR/ Supervisory Patent Examiner, Art Unit 1691
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