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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/25/2025 has been entered.
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 08/25/2025, wherein independent claims 1 and 17 are amended to recite an aprepitant emulsion comprising or consisting of specific amount of aprepitant and excipients prepared by a series of process steps.
Status of Claims
Claims 1, 13- 17 are pending in instant application .
Claim 16 remains withdrawn.
Claims 1, 13-15, and 17 are currently under examination in this office action..
Priority
This application 18/487,330 filed 10/16/2023 claims benefit of INDIA provisional Application 202241061823 filed 10/31/2022. Certified copies of foreign application required by 37 CFR 1.55 was filed on 11/09/2023.
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 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.
Claim Interpretation: Independent claims 1 and 17 are product-by-process claims wherein the patentability of a product does not depend on its method of production.
Instantly claimed stability profile of final aprepitant emulsion recited in claims 1 and 17, viscosity and zeta potential value recited in claims 13 and 15 are constructed as property of aprepitant emulsion product and/or intended result of manipulative preparation process, which does not necessarily contribute to the structural limitation of final product or additional patentable weight. Once the aprepitant injectable emulsion is formulated, measurement of stability, viscosity and zeta potential value is within the knowledge of an ordinary skilled in the art.
Claims 1, 13-15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Bhagwatwar et al. (US 2022/0160722 A1, Applicant’s IDS dated 10/16/2023, under “US Patent Application Publications”, Cite # 1), in view of Ottoboni et al. (US 2016/0082013 A1, hereafter “Ottoboni ‘013”) and evidenced by Cinvanti® aprepitant prescribing information 2019 by Heron Therapeutics (Applicant’s IDS dated 10/16/2023).
Bhagwatwar discloses stable emulsion formulations for the intravenous or parenteral administration of neurokinin-1 (NK-1) receptor antagonists(e.g. aprepitant) for treatment of emesis, method for preparing the stable NK-1 receptor antagonist emulsions and pharmaceutical formulations thereof (See abstract, [0015]-[0016], [0020]-[0025], [0032], [0074]-[0078],Examples 1-7, claims 1-20). Bhagwatwar teaches beneficial oil in water emulsion compositions of NK-1 antagonists(e.g. aprepitant) by using combinations of a phospholipid primary emulsifier/surfactant (e.g. egg lecithin) in combination with varying concentrations of one or more co-surfactants/secondary emulsifiers such as sodium oleate, ethanol (See [0013]). Bhagwatwar specifically discloses injectable emulsion formulations have an oil phase comprising aprepitant, oil, ethanol, egg lecithin, that is mixed with aqueous phase comprising sucrose and sodium oleate, and processed to form the emulsion formulation that may be stable for at least 12 months at refrigerated temperature(See abstract, [0015]-[0016], [0032], [0059]-[0066], [0074]-[0078], Examples 1-7, Table 1,3-4; claims 1-20).
Regarding the aprepitant composition final product, Bhagwatwar explicitly teaches final aprepitant emulsion product comprising aprepitant, egg lecithin, ethanol, soybean oil sucrose, and sodium oleate, at the amount within 5% of instantly claimed amount (See Table 1, Examples 1-2, 7; Table 3 and 4; claims 2-7, 12-15). As defined by instant specification [0060], “the term "about" means having a value falling within an accepted standard of error of the mean when considered by one of ordinary skill in the art. Frequently, the term "about" refers to ± 10%, preferably ±5% of the value or range to which it refers”.
For example, Bhagwatwar teaches Sample 2 in Table 3 and Scaled up Example 7 in Table 4, comprising: (a) aprepitant (7.2 mg), (b) egg lecithin ( 175mg, an emulsifier); (c) ethanol ( 27.78mg, co-emulsifier ); (d) soybean oil (94.4mg); (e) sodium oleate (5.7mg, buffering agent, 0.6 wt/wt %); (f) sucrose ( 55.56 mg); (g) water, wherein the pH of the composition ranges from 7.5-9.0 reads on “ about 7.5-11.0” recited in instant claim 14.
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455
629
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561
544
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Following table illustrated the side-by-side comparation of Bhagwatwar embodiment and instant claims:
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Regarding sodium oleate, Bhagwatwar teaches embodiments of stable emulsion product comprising 0.56 -0.67 wt/wt% sodium oleate (See Example 2 in Table 1, Samples 1-4 in Table 3, Example 7 in Table 4). Bhagwatwar teaches embodiments comprising sodium oleate levels ranging from 0.556% to 1.74% w/w, which showed promising stability, and acceptable syringeability, processability and redispersibility when compared to the commercial Cinvanti (aprepitant) formulation(See [0082]).
Regarding the manufacturing process, Bhagwatwar teaches preparation of oil phase comprising aprepitant, egg lecithin( Lipoid E 80) as emulsifier, ethanol as co-emulsifier and soybean oil, aqueous phase comprising sodium oleate and sucrose, mixing oil phase and aqueous phase under high shear homogenization, and fine emulsion preparation by high pressure homogenizer(See [0074]-[0078], Table 5, claim 18-20).
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As illustrated above, Bhagwatwar teaches preparation of oil phase and aqueous phase that read on instant recited steps, wherein sodium oleate and sucrose were dissolved in water, followed by high shear mixing with oil phase to prepare coarse emulsion. Bhagwatwar teaches various preparation processes mixing oil phase and aqueous phase wherein sodium oleate is in oil phase or in aqueous phase. Please note instant product claims are examined based on the structural limitations of final product. The limitation of intermediate process steps wherein oil phase and aqueous phase comprising specific emulsifiers/co-emulsifiers in each phase are NOT patentably distinctive structural limitation of final product.
Regarding the property / stability of final aprepitant composition, Bhagwatwar discloses embodiments of aprepitant injectable emulsion are physicochemically stable for at least 24 months at room temperature (25 degrees Celsius) without an increase in average droplet size or population of large-diameter fat globules above that allowed as stated in USP <729>( See [0070]). Bhagwatwar discloses reproducible batches of aprepitant injectable emulsion at large scale that are stable for extended period of time when stored at 5°± 3°C /60% RH (See [0084], Example 7, Tables 4, 6). Bhagwatwar discloses viscosity of the emulsion compositions with the desired zeta potential (Mv) ranging from -35 to -75 mV, e.g. -41.6 mV ( See [0080],Table 6)(which overlaps with “-25mV to about -40mV” of instant claim 15). Please note instantly claimed stability profile of final aprepitant emulsion recited in claims 1 and 17, viscosity and zeta potential value recited in claims 13 and 15 are construed as property of aprepitant emulsion product and/or intended result of manipulative preparation process, which does not necessarily contribute to the structural limitation of final product or additional patentable weight. Once the aprepitant injectable emulsion is formulated, measurement of stability, viscosity and zeta potential value is within the knowledge of an ordinary skilled in the art.
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, 1254, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112.01. Even if the stability, viscosity and zeta potential value are not identical to the value taught by the cited reference with regard to some unidentified characteristics, the differences between that which is disclosed and that which is claimed are considered to be slight , the claimed stability, viscosity and zeta potential value would have been obvious to those of ordinary skill in the art within the meaning of 35 USC §103.
Regarding general knowledge of aprepitant formulation, as disclosed by Bhagwatwar (See [0011]), “Beneficial emulsion formulations of aprepitant are commercially available in the United States from Heron Therapeutics under the brand name CINVANTI®. According to its label (Revised 10/2019), CINVANTI (aprepitant) injectable emulsion is a sterile, opaque, off-white to amber liquid in a single-dose vial for intravenous use. Each vial contains 130 mg aprepitant in 18 mL of emulsion. The emulsion also contains the following inactive ingredients: egg lecithin (2.6 g), ethanol (0.5 g), sodium oleate (0.1 g), soybean oil (1.7 g), sucrose (1 g), and water for injection (12 g). The emulsions are formulated to have final pH values in the range of 7.5-9.0 wherein the pH is adjusted using sodium oleate. The composition can be administered intravenously as an infusion or also as a bolus. According to the label, CINVANTI injectable emulsion vials must be refrigerated, store at 2° C.-8° C. (36° F.-46° F.), but can remain at room temperature up to 60 days”. An ordinary skilled in the art would have known injectable aprepitant emulsion are initially approved in US since 2003 and commercially available, such as Cinvanti® aprepitant injectable emulsion manufactured by Heron Therapeutics. It’s noted instant specification also use Cinvanti® aprepitant injectable emulsion as control (See Table 15-16). Thus, manufacturing process of Cinvanti® aprepitant emulsion disclosed by Heron Therapeutics, Ottoboni ‘013 is considered as general knowledge in preparing injectable aprepitant emulsion.
Regarding instantly claimed aprepitant emulsion and process steps, Ottoboni ‘013 teaches preparation of oil phase, aqueous phase, followed by homogenizing, wherein aqueous phase comprising sodium oleate and sucrose is added to the oil phase comprising aprepitant, egg lecithin (LIPOIDE 80), ethanol and soybean oil, followed by high-speed homogenization and high-pressure microfluidizer to produce fine aprepitant emulsion (See Examples 1-3): The aqueous phase was prepared by dissolving 5.60 g of sucrose and 0.500 g of sodium oleate in 70.0 ml of water for injection. This mixture was stirred at 300 rpm at room temperature for 30 min. The aqueous phase was then added to the oil phase and subsequently subjected to high-speed homogenization (Ultra-Turrax(RIKAT25) at a speed of 20,000 rpm for 1 min to produce the crude emulsion. It’s noted the ingredients in Ottoboni ‘013 also read on the instant claims except slightly different amount.
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To achieve desired property of stable injectable aprepitant emulsion (stability , viscosity, etc.), it would have been obvious and logical for a skilled artisan to further explore/optimize amount/ratio of ingredients, manipulate the steps/orders of mixing oil phase/aqueous phase in preparing emulsion process, based on the collective teachings of prior art and general knowledge of aprepitant injectable emulsion, e.g. manufacturing process of Cinvanti® aprepitant emulsion by Ottoboni’013. Bhagwatwar explicitly teaches aprepitant emulsion comprising aprepitant, egg lecithin, ethanol, soybean oil sucrose, and sodium oleate, that are comparable to commercial Cinvanti® aprepitant emulsion and Bhagwatwar Example 7 is large-scale process that are reproducible. A skilled artisan would be motivated to further optimize Bhagwatwar Example 7 for improved stability at r. t.
As stated in MPEP 2144.05, " 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 instant case, Bhagwatwar explicitly teaches aprepitant emulsion comprising the same amount of ingredients as instantly claimed aprepitant emulsion. Ottoboni ‘013 explicitly teaches manufacturing process of Cinvanti® aprepitant which is essentially the same as instant claimed steps except different amount. It’s noted the ingredients in Ottoboni ‘013 also read on the instant claims except slightly different amount. Both Bhagwatwar and Ottoboni ‘013 teach process of dissolving sodium oleate and sucrose in water before mixing with oil phase that read on instant recited steps. One of ordinary skill in the art would have had reasonable expectation of success in producing instantly claimed invention based on the combined teachings of prior art and general knowledge of injectable aprepitant emulsion, e.g. manufacturing process of Cinvanti® aprepitant emulsion by Ottoboni, wherein sucrose and sodium oleate was added in aqueous phase before mixing with oil phase comprising aprepitant, egg lecithin (LIPOIDE 80), ethanol, soybean oil, and homogenizing fine aprepitant emulsion, and arrive at instantly claimed invention.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's Remarks filed on 08/25/2025 have been fully considered, but they are NOT persuasive to overcome 35 USC § 103 rejection as elaborated above.
Applicant argues “Bhagwatwar does not disclose or suggest an aprepitant emulsion having the components in the amounts expressly recited in claims 1 and 17, as amended”(Remarks, page 5).
RESPONSE: Applicant’s argument is NOT persuasive. Bhagwatwar explicitly teaches final aprepitant emulsion product comprising aprepitant, egg lecithin, ethanol, soybean oil sucrose, and sodium oleate, at the amount within 5% of instantly claimed amount. Bhagwatwar teaches Sample 2 in Table 3 and Scaled up Example 7 in Table 4, comprising: (a) aprepitant (7.2 mg), (b) egg lecithin ( 175mg, an emulsifier); (c) ethanol ( 27.78mg, co-emulsifier ); (d) soybean oil (94.4mg); (e) sodium oleate (5.7mg, buffering agent, 0.6 wt/wt %); (f) sucrose ( 55.56 mg); (g) water, Please see following table for comparation:
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Applicant agrees the claims are product-by-process claims, but argues “Bhagwatwar does not disclose the steps for making the emulsion that are recited in the claims… The
method steps, however, are included in claims 1 and 17 because these steps are a defining factor
in how the recited superior stability is achieved at 25°C/60%RH”( Remarks, page 6).
RESPONSE: Applicant’s argument is NOT persuasive. Regarding process steps, Bhagwatwar teaches preparation of oil phase and aqueous phase that read on instant recited steps, wherein sodium oleate and sucrose were dissolved in water, followed by high shear mixing with oil phase to prepare coarse emulsion(See page 6, [0074]-[0078]).
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Although the step of mixing sodium oleate solution in water (stabilizer solution) to oil phase in large scale Example 7 of Bhagwatwar might vary, a skilled artisan would have known dissolving sodium oleate and sucrose in water before mixing with oil phase as taught by Bhagwatwar, which is also conventional process of preparing aqueous phase as taught by Ottoboni ‘013 in the process of preparing Cinvanti® aprepitant. It’s noted instant recited process does not disclose any specific parameter of process steps, such as temperature of mixing , homogenizing speed, etc. As such, instant claimed method steps as recited in claims 1 and 17 are NOT novel, not unexpected and might not be a defining factor in how the recited superior stability is achieved at 25°C/60%RH as Applicant argues. For example, it’s noted instant Composition E prepared by instantly claimed method shows phase separation even at 2-8ºC (See Table 7). Instant Composition G, H, I reformulated at larger batch size shows “Opaque off white to amber colored liquid free from visible particular matter”. It’s not clear if “the opaque liquid” is still “emulsion” with or without phase separation.
As elaborated in previous office action, according to M.P.E.P. § 2113. PRODUCT-BY-PROCESS CLAIMS ARE NOT LIMITED TO THE MANIPULATIONS OF THE RECITED STEPS, ONLY THE STRUCTURE IMPLIED BY THE STEPS. "[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) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009).
In instant case, Bhagwatwar explicitly teaches final aprepitant emulsion product comprising aprepitant, egg lecithin, ethanol, soybean oil sucrose, and sodium oleate, at the amount within 5% of instantly claimed amount. Although Bhagwatwar does not disclose the stability as instantly claimed, a skilled artisan would consider instant claimed composition as obvious alternative/optimization based on the combined teachings of Bhagwatwar, Ottoboni ‘013 and general knowledge of preparing aprepitant emulsion.
Applicant argues “there is nothing in Bhagwatwar that would suggest to a person of ordinary
skill in the art that the expressly recited process steps would provide an aprepitant emulsion
having the expressly recited stability”. Applicant further argues about the “phase separation of Bhagwatwar Example 7.… A person of ordinary skill in the art reading Bhagwatwar and trying to improve the stability of an aprepitant emulsion would have been motivated to use higher amounts of sodium oleate to improve the stability of an aprepitant emulsion, not to use the manufacturing steps expressly recited in the claims.”( Remarks, page 6-7).
RESPONSE: There is no requirement that the prior art explicitly suggests the specific modification. As stated in Federal Register /Vol. 89, No. 39 /Tuesday, February 27, 2024 /Notices, Page 14451. Flexible Approach to Providing a Reason To Modify the Prior Art: “The Federal Circuit makes it clear that the obviousness analysis is not ‘‘confined by a formalistic conception of the words teaching, suggestion, and motivation.’’ Intel Corp. v. Qualcomm Inc., 21 F.4th 784, 795 (Fed. Cir. 2021), quoting KSR, 550 U.S. at 419, 127 S. Ct. at 1741. To be sure, the Federal Circuit continues to use the word ‘‘motivation’’ in its obviousness jurisprudence. However, it is evident that the term is no longer understood in a rigid or formalistic way. See, for example, Norgren Inc. v. Int’l Trade Comm’n, 699 F.3d 1317, 1322 (Fed. Cir. 2012)”.
Please note test for obviousness is not that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. As explained in preceding section, instantly recited process steps of preparing oil phase, aqueous phases following by homogenizing is NOT inventive contribution in light of Bhagwatwar and Ottoboni ‘013, and considered as routine experimentation /optimization within the knowledge of skilled artisan in the art since it just involves conventional manufacturing process as in preparing Cinvanti® aprepitant taught by Ottoboni ‘013.
Regarding the phase separation of Bhagwatwar Example 7, there are many physical-chemical factors causing emulsion phase separation, e.g. density difference between phases, droplet size and distribution( larger droplets separate faster), interfacial properties, zeta potential, viscosity of the continuous phase (higher viscosity slowing separation), pH, etc. that are routinely optimized during the emulsion formulation process as taught by Bhagwatwar and Ottoboni ‘013 . The obviousness is not based on one or two exemplary embodiment, but based on the collective teachings of prior art and general knowledge of aprepitant formulation. Bhagwatwar discloses embodiments of aprepitant injectable emulsion are physico-chemically stable for at least 24 months at room temperature (25 degrees Celsius) without an increase in average droplet size or population of large-diameter fat globules above that allowed as stated in USP <729>( See [0070]). Bhagwatwar explicitly teaches embodiments of aprepitant emulsion final product that’s stable for at least 6 months without phase separation when stored at 5°±3°C. Bhagwatwar teaches embodiments showing promising stability, acceptable syringeability, processability and redispersibility comparable to the commercial Cinvanti (aprepitant) formulation. Cinvanti® 2019 also teaches the aprepitant injectable emulsion vials can be refrigerated, stored at 2°C-8°C (36°F-46°F) and can remain at room temperature up to 60 days (See 16. Storage and Handling and Bhagwatwar [0011]). Where 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. MPEP 2144.05. To further improve aprepitant emulsion stability at r. t based on Bhagwatwar’s teaching, a skilled artisan would not limit only to the amount/range/preparation process taught by prior art. Instead, a skilled artisan would have known to further optimization including manipulating the preparation process steps, such as mixing order of oil phase and aqueous phase at different temperature, increasing homogenizing rate to obtain smaller droplet, etc. based on general knowledge of emulsion formulation, such as Ottoboni ‘013.
The examiner does not dispute higher amounts of sodium oleate might improve the stability of an aprepitant emulsion as taught by Bhagwatwar. Please note Bhagwatwar disclosure of higher amount of sodium oleate (Table 2 and [0081]) is associated with the amount of egg lecithin in the absence of other co-emulsifier for desired Zeta potential/viscosity. A skilled artisan would know to use optimal amount of sodium oleate, e.g. 0.56 -0.67 wt/wt% in presence of other co-emulsifier (e.g. alcohol) as illustrated in Bhagwatwar Table 3-4 which is close to Cinvanti® aprepitant comprising 0.56% wt/wt of sodium oleate for optimal Zeta potential/viscosity. Please note optimizing amount of sodium oleate does not discourage POSA from experimentation/optimization of manufacturing steps, which in this case only involves following the conventional manufacturing process as taught by Ottoboni ‘013.
Applicant argues “Ottoboni does not remedy the deficiencies in Bhagwatwar… there is nothing that would motivate a person of ordinary skill in the art to replace the method of making disclosed in Bhagwatwar with the method of making disclosed in Ottoboni with a reasonable expectation that it would provide an aprepitant emulsion with the recited superior stability… There is nothing in Bhagwatwar or Ottoboni to suggest that the manufacturing steps will influence stability. The superior stability recited in the claims is completely unexpected (Remarks, page 7).
RESPONSE: As explained in preceding response, the combination of Bhagwatwar’s process with Ottoboni process is considered as routine experimentation/optimization within the general knowledge of a skilled artisan that do not need expressly teaching from the prior art.
Regarding instant claimed stability at r. t. Dubewar Declaration filed on 06/03/2024 argues that added sodium oleate prior to emulsion formation is the limitation that yields the unexpected result (Declaration para 10, 14). As explained before , Bhagwatwar teaches preparation of aqueous phase wherein sodium oleate and sucrose were dissolved in water before mixing with oil phase (See [0075]-[0078]). Ottoboni ‘013 also teaches sodium oleate was added in aqueous phase prior to emulsion formation. The combination of Bhagwatwar and Ottoboni ‘013 read on the process of adding sodium oleate prior to emulsion formation.
Bhagwatwar’s teaching is not limited to Example 7 as explained in previous response. Applicant’s argument of unexpected stability/result based on manufacturing steps should be compared with the product formulated/optimized based on combination of Bhagwatwar’s process and Ottoboni ‘013 process as a whole. In instant case, Bhagwatwar explicitly teaches aprepitant emulsion comprising the same amount of ingredients as instantly claimed aprepitant emulsion that are stable . Ottoboni ‘013 explicitly teaches manufacturing process of Cinvanti® aprepitant which is essentially the same as instant claimed steps except different amount. Both Bhagwatwar and Ottoboni ‘013 teach process of dissolving sodium oleate and sucrose in water before mixing with oil phase that read on instant recited steps. Since instant recited process step are not novel and NOT unexpected, the emulsion product formulated based on combined teachings of Bhagwatwar and Ottoboni ‘013 would be expected to exhibit similar stability profile as instantly claimed composition.
Applicant argues about hindsight reconstruction “In order to arrive at the claimed composition from Bhatwatwar and Ottoboni, requires selectively choosing the amounts of various components and the method of combining the components from the broad, general disclosure of these references, when there is no motivation or teaching to do so. Absent Applicant's disclosure as blueprint, a person of ordinary skill in the art, aware of Bhagwatwar and Ottoboni, would not arrive at the claimed formulation” (Remarks, page 8).
IN RESPONSE to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning , it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Please note the combination of ingredient as recited in instantly claimed composition are explicitly taught by Bhagwatwar which does not require selective choosing the amounts of various and components and combination from the broad general disclosure as Applicant argues.
IN SUMMARY: As stated in MPEP 2144.05 II, " 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." Instantly claimed aprepitant emulsion might exhibit better stability than exemplary sample of prior art. When considered as a whole, the alleged improved stability achieved by process steps is considered as better results of routine optimization of known formulation parameters disclosed by Bhagwatwar and Ottoboni ‘013 and not unexpected based on the teachings of prior art and general knowledge of aprepitant emulsion composition and preparation thereof. “Where 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".
Conclusion
No claims are allowed.
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/LIYUAN MOU/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628