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
The instant application was filed 27 July 2023 and is the national stage entry of PCT/CN2021/137170 filed 10 December 2021. The Applicant claims priority to foreign application CN202110122277.1 filed 28 January 2021. An English translated copy of the foreign document has been provided as of 19 February 2026. Therefore, the effective filing date of the instant application is 28 January 2021.
Examiner’s Note
The Applicant's amendments and arguments filed 19 February 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections not reiterated from previous office actions are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 19 February 2026, it is noted that claims 1, 2, 4, 7, 8, and 11 have been amended and claims 12 and 13 have been newly added. Support for the amendment(s) and new claim(s) can be found on at least pg. 4 of the specification. No new matter has been added.
Claim Rejections - 35 USC § 112
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.
Claim 13 is 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.
Regarding claim 13, the phrases "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claim(s) 1-6, 8, 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garti et al. (US 10568834 B2), as evidenced by Sahinovic et al. (Clinical Pharmacokinetics and Pharmacodynamics of Propofol, Clin Pharmacokinet., 2018), bbraunusa.com, and Liu et al. (Normal saline: Past, present, and future, Science Progress, 2023).
Garti teaches a liquid and water-free concentrate (entire teaching; col. 3, lns. 37-54) that may comprise MCT (col. 7, ln. 53), soy lecithin or egg (yolk) lecithin (col. 1, ln. 66; col. 8, ln. 36), ethanol (col. 12, ln. 37), and propofol (abs; entire teaching), which is insoluble in water (evidenced by Sahinovic, pg. 1540), addressing claim 5 and partially claim 1. Egg (yolk) lecithin addresses the phospholipid limitation of claim 1. The water-free concentrate is interpreted as anhydrous, addressing absolute ethanol in claim 1. The microemulsion spontaneously forms (col. 6, lns. 25-48), which is interpreted as a self-emulsifying in claim 1. The mix of phospholipid and non-phospholipid emulsifiers is interpreted as a composite emulsifier in claim 1. The composition may comprise PEG 15-hydroxystearate as a surfactant (col. 5, lns. 65-66), addressing Applicant’s election of the non-phospholipid emulsifier in claims 1-3. The amount of propofol may be 3-12% (col. 11, lns. 66-67). In other examples, lecithin may be in an amount of 1.88%, PEG 15-hydroxystearate in an amount of 68%, MCT oil in an amount of 7%, wherein the amounts of all the components add up to 100% (Table 1), partially addressing claims 4, 12, and 13. The composition may further comprise antioxidants and buffers, which are interpreted as pH adjusting agents (col. 12, lns. 56-66), addressing claim 6. The composition may be administered through injection and infusion (col. 14, lns. 15-26), and the droplet size may be 20 nm (col. 4, lns. 46-56), addressing claim 8. The formulation may be diluted with water, dextrose solution, and saline (col. 7, lns. 40-45), where dextrose solution is understood to be 5% dextrose and saline is understood to be 0.9% sodium chloride (evidenced by Liu, pg. 1 and bbraunusa.com, pg. 1), addressing claim 11.
Garti does not teach an exact combination of the components in claim 1. Garti does not specifically teach 20-50%, 20-40%, or 23-40% of a medium chain triglyceride in claims 4, 12, and 13, respectively. Garti does not specifically teach 30-60% or 30-50% of a non-phospholipid emulsifier in claims 12 and 13, respectively.
In regards to selecting the combination of a poorly soluble drug, medium chain triglyceride, absolute ethanol, and egg lecithin, “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G.Pro, 425 U.S. 273, 282 (1976)). “When the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various combinations of various disclosed ingredients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Garti teaches a liquid and water-free concentrate (col. 3, lns. 37-54) that may comprise MCT (col. 7, ln. 53), egg lecithin (col. 8, ln. 36), ethanol (col. 12, ln. 37), and propofol (abs; entire teaching), whereas the claimed invention is directed towards a liquid concentrate comprising a poorly soluble drug, a composite emulsifier, medium chain triglyceride, and absolute ethanol. Since Garti teaches the individual components of the claimed composition, it is obvious for one of ordinary skill in the art to select the different combinations of ingredients to arrive at the claimed invention with a reasonable expectation of success.
In regards to the amounts of components, such as MCT, in claims 4, 12, and 13, Garti teaches that the amount of propofol (hydrophobic drug) may be 3-12% (col. 11, lns. 66-67). In other examples, lecithin may be in an amount of 1.88%, PEG 15-hydroxystearate in an amount of 68%, MCT oil in an amount of 7%, 9.190% of ethanol, wherein the amounts of all the components add up to 100% (Table 1). Additionally, the weight ratio of the solvent to propofol may be 1.25:1 where the solvent may be MCT (claim 12 and col. 12, ln. 23). That being said and in lieu of objective evidence of unexpected results, the amounts can be viewed as a variable that achieves the recognized result of successfully making the hyaluronic acid-alendronate composition. The optimum or workable range of amounts can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of components, such as MCT, as nonobvious.
Claim(s) 1-8, 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garti et al. (US 10568834 B2) and Qian et al. (Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial-Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α, BioMed Research International, 2018), as evidenced by Sahinovic et al. (Clinical Pharmacokinetics and Pharmacodynamics of Propofol, Clin Pharmacokinet., 2018), bbraunusa.com, and Liu et al. (Normal saline: Past, present, and future, Science Progress, 2023).
In regards to claim(s) 1-6, 8, and 11, Garti, as applied supra, is herein applied in its entirety for its teachings of a liquid and water-free concentrate (col. 3, lns. 37-54) that may comprise MCT (col. 7, ln. 53), egg lecithin (col. 8, ln. 36), ethanol (col. 12, ln. 37), and propofol (abs; entire teaching).
Garti does not teach docetaxel or the exact amounts of components in claim 7.
Qian teaches an added benefit and effect for prostate cancer when propofol and docetaxel are used together (entire teaching; pgs. 1, 8).
Since Garti does not teach docetaxel in claim 7, one of ordinary skill in the art would have been motivated to use Qian’s teaching of docetaxel with propofol with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings since the combination of propofol and docetaxel has additional benefits for prostate cancer treatment.
In regards to the amounts of components in claim 7, as previously mentioned, Garti teaches that the amount of propofol (hydrophobic drug) may be 3-12% (col. 11, lns. 66-67). In other examples, lecithin may be in an amount of 1.88%, PEG 15-hydroxystearate in an amount of 68%, MCT oil in an amount of 7%, and 9.190% of ethanol, wherein the amounts of all the components add up to 100% (Table 1). Additionally, the weight ratio of the solvent to propofol may be 1.25:1 where the solvent may be MCT (claim 12 and col. 12, ln. 23). That being said and in lieu of objective evidence of unexpected results, the amounts can be viewed as a variable that achieves the recognized result of successfully making the hyaluronic acid-alendronate composition. The optimum or workable range of amounts can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of components, such as MCT, as nonobvious.
Response to Arguments
Applicant's arguments filed 19 February 2026 have been fully considered but they are not persuasive.
The Applicant argues that Garti does not teach a combination of the phospholipid and non-phospholipid from the claimed invention (Remarks, pgs. 7-8). The Applicant also argues that Example 1 of the instant application shows that using a single surfactant fails to prepare a stable microemulsion (remarks, pg. 8).
Applicant’s argument is not found persuasive. Garti teaches PEG 15-hydroxystearate as a surfactant (col. 15, ln. 65-col. 16, ln. 2) and egg yolk lecithin as a surfactant/co-surfactant (col. 8, lns. 35-39). Therefore, Garti broadly teaches different types of surfactants and co-surfactants in the instant claims. Furthermore, even if the teaching was limited to ethoxylated hydroxyl stearic acid as a surfactant and lecithin or phospholipids as a co-surfactants, the claim includes open “comprising” language. A skilled artisan would have therefore been easily led to the combination of phospholipid and non-phospholipid emulsifiers listed in the instant claims.
Additionally, Example 1 allegedly shows that using a single surfactant leads to unstable microemulsions. It is unsurprising that microemulsions would be further stabilized from additional co-surfactants or co-emulsifiers. Table 5 shows that the formulations comprising PEG 15-hydroxystearate and egg yolk lecithin (Formula 6) and PEG 15-hydroxystearate and soybean phospholipid (Formula 7) resulted in the most stable formulations with little to no change in particle size. Ali (Kolliphor HS 15 – An Enabler for Parenteral and Oral Formulations) suggests that nanoemulsions prepared using Kolliphor (Solutor) HS 15 and lecithin controlled the particle size well and created stable nanoemulsions (pg. 9). Therefore, a skilled artisan would have been motivated to use the combination of PEG 15-hydroxystearate and lecithin to improve the stability of their emulsion.
The Applicant argues that Garti does not teach that only MCT prepared a stable concentrate (Remarks, pg. 9).
Applicant’s argument is not found persuasive. Example 2 shows the same composition with different oils, such as MCT, LCT, olive oil, sunflower oil, etc. Table 7 shows that Formula 12, the formulation comprising MCT, has the best stability. Benita (US 5364632 A) teaches that MCT oil has many advantages over vegetable oil, such as lower susceptibility to oxidation, a higher specific density which leads to a more stable emulsion, less hydrophobicity which enables higher concentration of drugs, and lower viscosity which enables higher concentrations of the oily phase. Therefore, a skilled artisan would have been easily led to use MCT in their poorly-soluble drug emulsion composition and the Applicant’s results showing superior stability when MCT oil is not surprising or unexpected.
The Applicant argues that Example 3 shows that propylene glycol, glycerol, PEG200, PEG300, or PEG400 did not result in stable formulations (Remarks, pgs. 9-10).
Applicant’s argument is not found persuasive. Example 3 of the instant application shows the same composition with different co-emulsifiers, such as absolute ethanol, propylene glycol, glycerol, etc. (Table 8). Table 9 indicates that Formula 22, the formula comprising absolute ethanol, led to the most stable emulsion. Ferreira (Influence of Ethanol on Emulsions Stabilized by Low Molecular Weight Surfactants, Journal of Food Science, 2020) teaches that the addition of ethanol to emulsions decreased the droplet size and created a more stable formulation (abs). The addition of ethanol also contributes to the viscosity of the final emulsion, solubility of the surfactants, such as lecithin, density of the continuous phase, all which improve the stability of the emulsions (abs). Therefore, a skilled artisan would have been reasonable led to use ethanol as a co-solvent in their emulsion composition to improve stability and the Applicant’s results showing better stability using absolute ethanol is not surprising or unexpected.
Conclusion
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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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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