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 .
Summary
Claims 1, 3-4, and 6-21 are pending in this office action. Claims 15-21 are new. Claims 2 and 5 are cancelled. All pending claims are under examination in this application.
Priority
The current application was filed on September 5, 2023 is a 371 of PCT/CN2022/137727 filed on December 8, 2022. The current application claims foreign priority to CN202210391531.2 filed on April 14, 2022.
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 non-obviousness.
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 1, 3-4, and 6-21 are rejected under 35 U.S.C. 103 as being unpatentable over He et al. (CN107281100A) in view of Liu et al. (US2021/0299059A1, published in September 2021) and Li et al. (CN109394685A).
[The Examiner is going to introduce each reference and then combine them where appropriate to reject the instant claims.]
1. He et al.
He et al. is considered the closest prior art as it teaches preparation method of insoluble drug nanosuspension (see title). Furthermore, He et al. disclose that the invention discloses a preparation method of insoluble drug nanosuspension. The preparation method comprises the following steps: firstly, dispersing an insoluble drug into an aqueous solution containing a stabilizer to obtain an initial suspension, wherein the mass ratio of the insoluble drug to the stabilizer is 2.5-1 to 8-1; secondly, carrying out high-speed shearing on the initial suspension obtained in the first step to obtain coarse suspension; thirdly, carrying out micro-jet high-pressure homogenizing on the coarse suspension obtained in the second step to obtain the insoluble drug nanosuspension, wherein the drug concentration of the insoluble drug nanosuspension is 150 to 300 mg/mL. The preparation method disclosed by the invention has the advantages of no use of an organic solvent, simple preparation technology, good repeatability and good safety; in addition, the drug concentration of the prepared insoluble drug nanosuspension can reach 150 to 300 mg/mL, the particle size of the drug is small and the distribution of the drug is uniform (see abstract).
2. Liu et al.
Liu et al. teach an injectable pharmaceutical composition and preparation method thereof (see title). In addition, Liu et al. disclose an injectable pharmaceutical composition and a preparation method therefor. Specifically, the pharmaceutical composition comprises apixaban nanoparticles, a surface stabilizer, and may further comprise a sedimentation inhibitor. The pharmaceutical composition has good stability and is suitable for industrial mass production (see abstract).
3. Li et al.
Li et al. teach pharmaceutical composition of VEGFR inhibitor and preparation method of pharmaceutical composition (see title). Additionally, Li et al. disclose that the invention relates to pharmaceutical composition of a VEGFR inhibitor and a preparation method of the pharmaceutical composition. Specifically, the invention relates to composition comprising N-[4-(1-cyanocyclopentyl)phenyl]-2-(4-pyridylmethyl)amino-3-pyridinecarboxamide with the particle size D90 smaller than about 10 mm and a preparation method of the pharmaceutical composition. Compared with a commercial preparation, the pharmaceutical composition has improved individual difference (see abstract).
Combination of He et al. and Liu et al.
Regarding instant claim 1, He et al. and Liu et al. teach a pharmaceutical composition for injection. The necessary citations of He et al. and Liu et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
He et al. and Liu et al. Citations
A pharmaceutical composition,
He et al. disclose a preparation method of insoluble drug nanosuspension. The preparation method comprises the following steps: (1) dispersing an insoluble drug into an aqueous solution containing a stabilizer to obtain an initial suspension, wherein the mass ratio of the insoluble drug to the stabilizer is 2.5-1 to 8-1; (2) carrying out high-speed shearing on the initial suspension obtained in the first step to obtain coarse suspension; (3) carrying out micro-jet high-pressure homogenizing on the coarse suspension obtained in the second step to obtain the insoluble drug nanosuspension, wherein the drug concentration of the insoluble drug nanosuspension is 150-300 mg/mL (see abstract within He et al.). The stabilizer consists of surfactant (equivalent to a primary stabilizer) and polymeric suspending agent (equivalent to a secondary stabilizer) in mass ratio of 4:1-0.25:1. The insoluble drug is selected from the group consisting of aprepitant. The surfactant is one or more of a Tween surfactant, sodium deoxycholate, and the like. Tween surfactant is preferably one or more of Tween-20, Tween-40, Tween-60, and Tween-80. The polymeric suspending agent is selected from polyvinylpyrrolidone and the like. The polyvinylpyrrolidone is preferably polyvinylpyrrolidone-K30. The mass ratio of insoluble drug to stabilizer is 6:1 to 3:1, preferably 4:1. The insoluble drug nanosuspension has drug particle size D50 of 400-700 nm, preferably 500-600 nm (see claims 1-2, 4-7, and 10 within He et al.).
He et al. neither discloses the composition comprising sodium deoxycholate as a primary stabilizer and povidone as a secondary stabilizer, nor discloses a method of preparing the pharmaceutical composition, injection and freezedried powder injection.
However, Liu et al. disclose all of the above mentioned deficiencies.
comprising aprepitant, a primary stabilizer, and a secondary stabilizer,
He et al. supplies the use of the poorly soluble drug aprepitant (see claim 2 within He et al.).
Liu et al. provides an injectable pharmaceutical
composition comprising the (poorly water-soluble drug) apixaban nanoparticles and a surface stabilizer (see paragraph [0005] within Liu et al.).
wherein the primary stabilizer comprises sodium deoxycholate and the secondary stabilizer is povidone, and a mass ratio of the sodium deoxycholate to the povidone is in the range from 1:(1-7).
Liu et al. disclose that the surface stabilizer may be one or more of nonionic surface stabilizers, anionic surface stabilizers, cationic
surface stabilizers and zwitterionic surface stabilizers. The surface stabilizer may be selected from one or more of povidone, polyvinyl alcohol, docusate sodium,
hydroxypropyl methylcellulose, Tween 80, poloxamer, polyethylene glycol 15-hyclroxystearate, lecithin, sodium
deoxycholate, sodium cholate, preferably one or more of poloxamer, sodium deoxycholate, povidone, docusate sodium and Tween 80, further preferably sodium deoxycholate
and povidone (see paragraph [0010-0011] within Liu et al.).
Liu et al. disclose that the present invention provides a pharmaceutical composition comprising poorly water-soluble drug (aprepitant), povidone, and sodium deoxycholate. Further, the weight ratio of the poorly water-soluble drug (aprepitant) to the povidone may be selected from 1:0.01 to 1:10; the weight ratio of the poorly water-soluble drug (aprepitant) to the sodium deoxycholate may be selected from 1:0.01 to 1:10 (see paragraph [0040] within Liu et al.). For example, the following hypothetical ratio can be obtained:
Primary stabilizer; 2 parts povidone
Secondary stabilizer; 10 parts sodium deoxycholate
Ratio; 1:5 (primary stabilizer:secondary stabilizer)
Thus, a skilled artisan (POSITA; person having ordinary skill in the art) would combine the teachings of He et al. and Liu et al. through the substitution of the poorly soluble drug apixaban disclosed by Liu et al. with aprepitant disclosed by He et al. under routine experimental conditions.
Therefore, a skilled artisan (POSITA) would use the He et al. and Liu et al. references to teach every element of instant claim 1.
The remaining instant claims within this 35 U.S.C. § 103 section are either directly or indirectly dependent on instant claim 1 and are taught in full by the combination of He et al. and Liu et al.
Regarding instant claim 3, He et al. and Liu et al. teach wherein a mass ratio of the primary stabilizer to the secondary stabilizer is in the range from 1:(2-7). Liu et al. disclose that the present invention provides a pharmaceutical composition comprising poorly water-soluble drug (aprepitant), povidone, and sodium deoxycholate. Further, the weight ratio of the poorly water-soluble drug (aprepitant) to the povidone may be selected from 1:0.01 to 1:10; the weight ratio of the poorly water-soluble drug (aprepitant) to the sodium deoxycholate may be selected from 1:0.01 to 1:10 (see paragraph [0040] within Liu et al.). For example, the following hypothetical ratio can be obtained:
Primary stabilizer; 2 parts povidone
Secondary stabilizer; 10 parts sodium deoxycholate
Ratio; 1:5 (primary stabilizer:secondary stabilizer)
Regarding instant claim 4, He et al. and Liu et al. teach wherein the povidone has a molecular weight of less than 45000. The commercially available povidones from Sigma-Aldrich include (CAS 9003-39-8) average molecular weights of 40,000 and 10,000. Additionally, povidone K30 is available. Therefore, a skilled artisan (POSITA) would incorporate these commercially available povidones under routine experimental conditions (see PTO-892 NPL V; Non-Final).
Regarding instant claim 6, He et al. and Liu et al. teach wherein the pharmaceutical composition further comprises one or more selected from a pH adjuster and an osmotic pressure regulator. The pH adjusters disclosed within instant claim 6 are standard reagents within an organic chemistry lab, and thus would be easily accessible to a skilled artisan. Additionally, Liu et al. disclose the use of mannitol and glycerin (equivalent to glycerol) (see claim 12 within Liu et al.). Moreover, Lui et al. disclose use of the osmoregulator, sodium chloride (see Table 1 within Liu et al.).
Regarding instant claim 7, He et al. and Liu et al. teach wherein the pharmaceutical composition is in the form of a suspension. A skilled artisan (POSITA) would attempt to obtain physiologic pH of 7.4 for a pharmaceutical composition for injection under routine conditions. Furthermore, Liu et al. disclose a D50 value of less than 500 nm, less than 200 nm, or less than 170 nm (see claim 9 within Liu et al.).
Regarding instant claims 8 and 9, He et al. and Liu et al. teach the pharmaceutical composition comprising: 1 part by weight of the aprepitant; 0.04-0.45 parts by weight of the primary stabilizer; 0.04-3.2 parts by weight of the secondary stabilizer; 0.001-0.04 parts by weight of the pH adjuster; 0.005-0.05 parts by weight of the osmotic pressure regulator; and water. The following bullet points illustrate a representative pharmaceutical composition for injection:
1 part by weight aprepitant
Primary stabilizer; weight ratio of the poorly water-soluble drug (aprepitant) to the povidone may be selected from 1:0.01 to 1:10 (see paragraph [0040] within Liu et al.).
Secondary stabilizer; the weight ratio of the poorly water-soluble drug (aprepitant) to the sodium deoxycholate may be selected from 1:0.01 to 1:10 (see paragraph [0040] within Liu et al.).
pH adjuster [0.001-0.04 parts]; as needed (0.1-4 wt%) to reach physiologic pH (see the discussion within instant claim 6).
osmotic pressure regulator [0.005-0.05]; as needed (0.5-5 wt%) to reach the desired osmotic pressure for injection (see the discussion within instant claim 6).
Water; the remainder of the pharmaceutical composition weight is the solvent water (see Table 1 and paragraph [0083] within Liu et al.; also see paragraph [0059] and [0065] within He et al.).
Regarding instant claim 10, He et al. and Liu et al. teach an aprepitant injection, comprising the pharmaceutical composition of claim 1. Please see the discussion and citations within instant claim 1. He et al. disclose that drug nanosuspensions consist only of drugs and a small amount of stabilizers, require no carriers, and use a small amount of excipients. High-concentration drug nanosuspensions can reduce the volume of administration and are safer. This dosage form has significant advantages for drugs that require small-volume injections, such as intramuscularly, subcutaneously, or intradermally (see paragraph [0010] within He et al.).
Regarding instant claim 11, He et al. and Liu et al. teach ) A method of preparing the pharmaceutical composition of instant claim 1, comprising: step (1): dissolving a primary stabilizer and a secondary stabilizer in water for injection, followed by stirring until complete dissolution, optionally adding a pH adjuster, and adding an aprepitant for homogeneous dispersion to form an initial suspension; step (2): adding a milling medium into a milling chamber, and adding the initial suspension into a milling cylinder to start milling at velocity in the range from 6.0m/s to 17.0m/s, to obtain an aprepitant nanosuspension with a D50 less than 200 nm; and step (3) filling the aprepitant nanosuspension into a vial or an ampoule upon sterilization and filtration. He et al. disclose the following preparation method:
The preparation method comprises the following steps: (1) dispersing an insoluble drug into an aqueous solution containing a stabilizer to obtain an initial suspension, wherein the mass ratio of the insoluble drug to the stabilizer is 2.5-1 to 8-1; (2) carrying
out high-speed shearing on the initial suspension obtained in the first step to obtain coarse suspension; (3) carrying out micro-jet high-pressure homogenizing on the coarse suspension obtained in the second step to obtain the insoluble drug nanosuspension, wherein the drug concentration of the insoluble drug nanosuspension is 150-300mg/mL. The stabilizer consists of surfactant (equivalent to a primary stabilizer) and polymeric suspending agent (equivalent to a secondary stabilizer) in mass ratio of 4:1-0.25:1 (see claim 1 and abstract within He et al.).
Liu et al. disclose a method incorporating milling to prepare the pharmaceutical composition:
A method for preparing the pharmaceutical composition of claim 1, comprising co-milling the surface stabilizer and the poor water-soluble drug (aprepitant) to prepare the pharmaceutical composition comprising a poor water-soluble drug (aprepitant) (see claim 24 within Liu et al.).
Methods of preparing insoluble drug nanosuspensions include media milling methods, high pressure homogenization methods, and the like. Media milling methods are mainly mechanical forces generated by bringing milling media through milling rods, the drug molecules interact with the milling media for the purpose of particle size reduction. Parameters needed to be adjusted for media milling methods include milling media size and loading, milling speed and time, flow rate and temperature, etc. Liu et al. teach that methods for preparing pharmaceutical composition comprising aprepitant can be selected from media milling methods, and the pharmaceutical composition can be prepared as an injectable pharmaceutical formulation (see claims 10, 24-27, and 29-31 within Liu et al.). It would be obvious for the skilled person in the art to prepare the pharmaceutical compositions by using media milling methods.
Additionally, Liu et al. disclose the correct D50 (see the discussion and citations within instant claim 7). Also, packaging of the pharmaceutical composition for injection (the aprepitant nanosuspension) within a vial or an ampoule upon sterilization and filtration, is standard or common protocol.
Regarding instant claim 12, He et al. and Liu et al. teach wherein the milling medium is zirconia beads and/or polystyrene beads. For a discussion of milling, please see instant claim 11. Also see paragraph [0083] within Liu et al. regarding grinding beads. Both zirconia and polystyrene beads are commonly used in milling technologies (see PTO-892 NPL W), and therefore, would be available to a skilled artisan (POSITA).
Regarding instant claims 13 and 14, He et al. and Liu et al. teach an aprepitant freeze-dried powder injection, comprising a freeze-dried powder prepared by adding a lyoprotectant into the pharmaceutical composition of instant claim 1 followed by freeze-drying. Freeze-drying is common within the art. Liu et al. disclose the use of a freeze-drying step in preparing the pharmaceutical composition for injection (see Table 4 within Liu et al.). Further, Liu et al. disclose the use of the lycoprotectants mannitol and sucrose (see Table 4 within Liu et al.).
Regarding instant claim 15, He et al. and Liu et al. teach wherein the povidone has a molecular weight of less than 15000. The commercially available povidones from Sigma-Aldrich include (CAS 9003-39-8) include average molecular weights of 10,000.
Regarding instant claim 16, He et al. and Liu et al. teach wherein the povidone has a molecular weight of less than 4000. ThermoFisher Scientific provides commercially available povidone having an molecular weight of 3500 (see PTO-892 NPL W).
Regarding instant claim 17, He et al. and Liu et al. teach wherein the povidone is one or more selected from the group consisting of povidone K30, povidone K18, povidone K17, povidone K15, and povidone K12. He et al. disclose the polyvinyl pyrrolidone is preferably polyvinyl pyrrolidone-K30 (see paragraph [0022] within He et al.). Additionally, MedChemExpress sells povidone K-15 (see PTO-892 NPL V).
Regarding instant claim 18, He et al. and Liu et al. teach wherein the pH adjuster is one or more selected from the group consisting of hydrochloric acid, sodium hydroxide, citric acid, a citrate, tartaric acid, a tartrate, acetic acid, lactic acid, phosphoric acid, and a phosphate; and the osmotic pressure regulator is one or more selected from the group consisting of sodium chloride, glucose, mannitol, and glycerin. The pH adjusters disclosed within instant claim 18 are standard reagents within an organic chemistry lab, and thus would be easily accessible to a skilled artisan. Additionally, Liu et al. disclose the use of mannitol and glycerin (equivalent to glycerol) (see claim 12 within Liu et al.). Moreover, Lui et al. disclose use of the osmoregulator, sodium chloride (see Table 1 within Liu et al.).
Combination of He et al., Liu et al., and Li et al.
Regarding instant claims 19-21, He et al., Liu et al., and Li et al. teach wherein the suspension has a pH value in the range from 6.0 to 8.5; and/or the aprepitant in the suspension has a D50 less than 200 nm. Liu et al. disclose the average particle size or D50 of the apixaban nanoparticle may be less than 500 nm, preferably less than 200 nm, further preferably less than 170 nm, further preferably less than 160 nm, further more preferably less than 150 nm (see paragraph [0038] within Liu et al.). In addition, Liu et al. disclose adjusting the pH to a range of 7.0 to 8.0 with disodium hydrogen phosphate (see paragraph [0079] within Liu et al.). Furthermore, Li et al. disclose the particle size D50 value of the active ingredient in the pharmaceutical composition of the present invention is less than about 1 μm, and the D50 value is preferably less than about 1 μm, less than about 900 nm, less than about 800 nm, less than about 700 nm, less than about 600 nm, less than about 500 nm, less than about 450 nm, less than about 400 nm, less than about 350 nm, less than about 300 nm, less than about 250 nm, less than about 200 nm, less than about 150 nm, less than about 100 nm or less…(see paragraph [0013] within Li et al.).
Analogous Art
The He et al., Liu et al., and Li et al. references are directed to the same field of endeavor as the instant claims, that is, a pharmaceutical composition, comprising aprepitant, a primary stabilizer, and a secondary stabilizer, wherein the primary stabilizer comprises sodium deoxycholate and the secondary stabilizer comprises povidone.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the drug nanosuspension disclosed by He et al., using the teachings of Liu et al., and further in light of the claim-specific feature described in Li et al., in order to arrive at the subject matter of the instant claims.
The He et al., Liu et al., and Li et al. references all have considerable overlap for the drug nanosuspension arts. In this instance, He et al. supplies the use of the drug aprepitant, Liu et al. teaches the use of an injectable pharmaceutical composition containing both stabilizers sodium deoxycholate and povidone, while Li et al. supplies a claim-specific example having the appropriate D50. All references are directed to the drug nanosuspension arts and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the three references when seeking to modify a drug nanosuspension.
Starting with He et al., the skilled person only had to try the necessary claim limitations disclosed by both Liu et al. and Li et al. The combination of He et al., Liu et al., and Li et al. would allow one to arrive at the present application without employing inventive skill. This combination of the drug nanosuspension taught by He et al. along with the use of the necessary claim limitations taught by both Liu et al. and Li et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the drug nanosuspension disclosed by He et al. with the use of the necessary claim limitations taught by both Liu et al. and Li et al. Incorporating the disclosure of He et al. into the drug nanosuspension presented by Liu et al. and Li et al. represents a predictable use of prior art elements according to their established functions, consistent with MPEP §2143 and KSR.
Furthermore, the additional claim limitations taught by Liu et al. and Li et al. would have been viewed by a POSITA as routine design optimizations or known modifications for drug nanosuspensions. Implementing these features in He et al.’s drug nanosuspension would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of He et al., supplemented by Liu et al. and Li et al. provides all the elements of the claimed invention. The resulting drug nanosuspension constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
In the context of instant method claims 11-12 the desired purpose defines an effect that arises from and is implicit in the method step(s). Thus, where the purpose is limited to stating a technical effect that inevitably occurs during the performance of the claimed method step(s), and is therefore inherent in that/those step(s), that technical effect is not limiting to the subject-matter of the claim. Thus, the present method claim, defining the application/use of the composition according to the prior art, and defining its purpose as "use", is anticipated by any document of the state of the art describing a method of application/use although not mentioning this specific use.
Response to Arguments
Applicant's arguments filed November 7, 2025 have been fully considered but they are not persuasive.
The Applicant’s claim amendments were sufficient to address the 35 U.S.C. 112(b) rejections. Therefore, the 35 U.S.C. 112(b) rejections from the Non-Final office action dated September 17, 2025 are withdrawn.
The Applicant’s claim amendments did necessitate a new ground of rejection.
Applicant Argument: The Applicant argues that the He et al. reference does not disclose the claimed combination.
Examiner’s Rebuttal: Since the Examiner has established a 35 U.S.C. §103 rejection using both the He et al. and Liu et al. citations to reject instant claim 1, He et al. is not required to provide all elements to the invention. Also, He et al. is not required to present experimental data supporting the stabilization effect to reject the instant claim.
Applicant Argument: The Applicant argues that the Liu et al. reference uses a different active ingredient than that of the present application (apixaban v. aprepitant). Each pharmaceutical has a different mode of action. Therefore, there would be no reasonable chance of success that this set of stabilizers (sodium deoxycholate and povidone) would be effective for the active ingredient of the instant application.
Examiner’s Rebuttal: The Examiner respectfully disagrees. Liu et al. disclose the use of both stabilizers required by the instant application. Despite the differences in the biological mode of action of the two drugs, a skilled artisan (POSITA) using the He et al. reference would employ routine experimentation to ascertain the stabilization effect of sodium deoxycholate and povidone supplied by the Liu et al. reference.
Applicant Argument: The Applicant argues that there is no motivation to combine or reasonable chance of success for the He et al. and Liu et al. references.
Examiner’s Rebuttal: The Examiner respectfully disagrees. He et al. uses the active ingredient, aprepitant, and the stabilizer povidone. Liu et al. disclose the use of both sodium deoxycholate and povidone for a different active ingredient. Routine experimentation by a skilled artisan (POSITA) would be used be used to determine if the sodium deoxycholate and povidone would be suitable for aprepitant.
Applicant Argument: The Applicant argues that the unexpected results by the inventors support patentability of the instant application.
Examiner’s Rebuttal: The Examiner respectfully disagrees. The unexpected results are interesting however, they are not strong enough to withdraw the prior art of record [Evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (Claims directed to a method of effecting analgesia without producing physical dependence by administering the levo isomer of a compound having a certain chemical structure were rejected as obvious over the prior art. Evidence that the compound was unexpectedly nonaddictive was sufficient to overcome the obviousness rejection. Although the compound also had the expected result of potent analgesia, there was evidence of record showing that the goal of research in this area was to produce an analgesic compound which was nonaddictive, enhancing the evidentiary value of the showing of nonaddictiveness as an indicium of nonobviousness.) see MPEP 716.02(c)].
Furthermore, Applicant fails to show comparison data with the closest prior art to support these unexpected results. Example 9 presents comparison vascular irritation data between the aprepitant formulation and a fosaprepitant dimeglumine formulation, but there is no description for the comparison formulation other than to say that it is “marketed.” Example 8 states, “The results of animal PK studies showed that the nanosuspension injection prepared in Example 4 was equivalent to and could be equivalent substitution of the fosaprepitant dimeglumine freeze-dried powder injection in terms of PK in animals, but had smaller irritations at injection sites and thus safer for patients to use than the marketed fosaprepitant dimeglumine injection or aprepitant fat emulsion injection.
The Examiner has many questions regarding this marketed formulation. Is it the best formulation in the art thus far? Is this irritation result a major problem with this formulation that the present invention solves? Is this the only formulation the present invention is trying to beat? What is the size (diameter) of this formulation?
Therefore, the 35 U.S.C. §103 rejection is maintained for instant claims 1, 3-4, and 6-21.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615