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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 28 July 2026 has been entered.
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 28 July 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 Rejections not reiterated from previous office actions are hereby withdrawn.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 28 July 2026, it is noted that claims 1 and 13 have been amended and no new claims have been added or canceled. The amendments have been made for clarity purposes. No new matter has been added.
Declaration
The declaration under 37 CFR 1.132 filed 28 July 2026 is insufficient to overcome the rejection of claims 1-8, 10-13 based upon Garti et al. as set forth in the last Office action because:
The Applicant argues unexpected results regarding the stability of the microemulsion (Declaration, pg. 3, para. 6). The Applicant alleges that the instant invention is capable of forming stable microemulsions upon dilution when poorly soluble drugs, such as celecoxib, paclitaxel, docetaxel, etc. are used, as shown in Example 4 of the instant application (Declaration, pg. 3, para. 6). The system in Garti is allegedly designed only for propofol, where when the Applicant tested eight poorly soluble drugs with Garti’s concentrate system, only ibuprofen resulted in a clear solution upon dilution (Declaration, pg. 3, para. 7). Example 6 of the instant specification allegedly shows that the propofol concentrate has less free propofol and lower hemolysis rate than the B6 concentrate of Garti (Declaration, pgs. 3-4, para. 8).
Applicant’s argument is not found persuasive. The Applicant refers to Example 4 of the instant specification, which shows the stability of the emulsions for different liquid concentrates comprising various poorly soluble drugs. For example, Liquid concentrate 1 comprises celecoxib and results in an emulsion with slightly blue opalescence and no drug precipitation, Liquid concentrate 3 comprises paclitaxel results in a white emulsion with no drug precipitation, Liquid concentration 4 results in an emulsion with slightly blue opalescence with no drug precipitation, and Liquid concentrate 5 results in an emulsion with obvious slightly blue opalescence and no drug precipitation. These are some examples of poorly soluble drugs that form stable microemulsions upon dilution, according to the Declaration. However, Liquid concentrate 26 comprises propofol and also results in a white emulsion with no drug precipitation.
Since 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), and instant claim 1 is broad to any poorly soluble drug, the instant claims are rendered obvious in light of Garti’s teaching.
Furthermore, any evidence of stable microemulsions does not have a causal relationship with the merits and scope of the claimed invention, which is, broadly, a liquid concentrate consisting of any poorly soluble drug. As such, the data are not commensurate in scope with the claims.
“For objective evidence of secondary considerations to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention.” Wyers v. Master Lock Co., 616 F.3d 1231, 1246 [95 USPQ2d 1525] (Fed. Cir. 2010) (quotation omitted). Where the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention. Tokai Corp. v. Easton Enters., Inc., 632 F.3d 1358, 1369 [97 USPQ2d 1673] (Fed. Cir. 2011) (“If commercial success is due to an element in the prior art, no nexus exists.”); Ormco Corp., 463 F.3d at 1312 (“[I]f the feature that creates the commercial success was known in the prior art, the success is not pertinent.”); In re Woodruff, 919 F.2d 1575, 1578 [16 USPQ2d 1934] (Fed. Cir. 1990).
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 5 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 5, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations 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, 11-13 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).
Regarding claim 1, Garti teaches a liquid and water-free concentrate (entire teaching; col. 3, lns. 37-54) that may comprise (2) MCT (col. 7, ln. 53), (1) soy lecithin or egg (yolk) lecithin (a phospholipid) (col. 1, ln. 66; col. 8, ln. 36), (3) ethanol (col. 12, ln. 37), and propofol (poorly-soluble drug) (abs; entire teaching), which is insoluble in water (evidenced by Sahinovic, pg. 1540). The water-free concentrate is interpreted as anhydrous. The microemulsion spontaneously forms (col. 6, lns. 25-48), which is interpreted as self-emulsifying. The mix of phospholipid and non-phospholipid emulsifiers is interpreted as a composite emulsifier. The composition may comprise (1) PEG 15-hydroxystearate as a surfactant (col. 5, lns. 65-66), addressing Applicant’s election of the non-phospholipid emulsifier.
Regarding claims 2 and 3, the composition may comprise (1) PEG 15-hydroxystearate as a surfactant (col. 5, lns. 65-66).
Regarding claim 4, 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).
Regarding claim 5, the poorly-soluble drug may be propofol (abs).
Regarding claim 6, the composition may further comprise antioxidants and buffers, which are interpreted as pH adjusting agents (col. 12, lns. 56-66).
Regarding claim 8, 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).
Regarding claim 11, 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).
Regarding claims 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).
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 in claim 1, “[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) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garti et al. (US 10568834 B2), as applied to claim(s) 1-8, 11-13 above, in view of 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 11-13, 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 28 July 2026 have been fully considered but they are not persuasive.
The Applicant argues that Garti teaches a combination of a surfactant and a co-surfactant may be a combination of two different types of phospholipids (Remarks, pgs. 8-9).
Applicant’s argument is not found persuasive. Garti teaches an embodiment comprising propofol, polyethylene glycol 15-hydroxystearate (Solutol HS 15), MCT, at least one co-surfactant, and at least one co-solvent (col. 6, lns. 3-11), wherein the co-surfactant may be a phospholipid (col. 8, lns. 5-8) and the co-solvent may be ethanol (col. 8, lns. 40-44).
The Applicant argues that Garti teaches different types of solvents/oils and co-solvents (Remarks, pgs. 9-10).
Applicant’s argument is not found persuasive. It is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).
The Applicant argues that Garti emphasizes the importance of specific combinations of components (Remarks, pgs. 10-11).
Applicant’s argument is not found persuasive. The Applicant is erroneously pointing to narrow embodiments expressly disclosed within the prior art reference as representing the sum total of information conveyed by each. Art is art, not only for what it expressly teaches, but also for what it would reasonably suggest to the skilled artisan, including alternative or non-preferred embodiments (see MPEP § 2123).
The Applicant argues that Garti teaches that PG and PEG400 are included in certain concentrate formulations in Example 1 and that these are important key components that are not included in the present application (Remarks, pg. 11).
Applicant’s argument is not found persuasive. In response to the Applicant's argument that the references fail to show certain features of applicant’s invention, it is reminded that to properly teach away, the prior art reference must criticize, discredit, or otherwise discourage the solution sought. Merely teaching alternatives does not do this (see MPEP 2145 (X)(D)).
The Applicant argues that, as stated in the Declaration, the concentrate system of Garti is specifically designed for propofol and the present invention yielded unique results regarding the microemulsion stability (Remarks, pg. 12).
Applicant’s argument is not found persuasive. As stated above, the Applicant refers to Example 4 of the instant specification, which shows the stability of the emulsions for different liquid concentrates comprising various poorly soluble drugs. For example, Liquid concentrate 1 comprises celecoxib and results in an emulsion with slightly blue opalescence and no drug precipitation, Liquid concentrate 3 comprises paclitaxel results in a white emulsion with no drug precipitation, Liquid concentration 4 results in an emulsion with slightly blue opalescence with no drug precipitation, and Liquid concentrate 5 results in an emulsion with obvious slightly blue opalescence and no drug precipitation. These are some examples of poorly soluble drugs that form stable microemulsions upon dilution, according to the Declaration. However, Liquid concentrate 26 comprises propofol and also results in a white emulsion with no drug precipitation.
Since 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), and instant claim 1 is broad to any poorly soluble drug, the instant claims are rendered obvious in light of Garti’s teaching.
Furthermore, any evidence of stable microemulsions does not have a causal relationship with the merits and scope of the claimed invention, which is, broadly, a liquid concentrate consisting of any poorly soluble drug. As such, the data are not commensurate in scope with the claims.
“For objective evidence of secondary considerations to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention.” Wyers v. Master Lock Co., 616 F.3d 1231, 1246 [95 USPQ2d 1525] (Fed. Cir. 2010) (quotation omitted). Where the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention. Tokai Corp. v. Easton Enters., Inc., 632 F.3d 1358, 1369 [97 USPQ2d 1673] (Fed. Cir. 2011) (“If commercial success is due to an element in the prior art, no nexus exists.”); Ormco Corp., 463 F.3d at 1312 (“[I]f the feature that creates the commercial success was known in the prior art, the success is not pertinent.”); In re Woodruff, 919 F.2d 1575, 1578 [16 USPQ2d 1934] (Fed. Cir. 1990).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danielle Kim whose telephone number is (571)272-2035. The examiner can normally be reached M-F: 9-5 p.m. PST.
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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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