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 01 June 2022 and is the national stage entry of PCT/CN/2020/133470 filed 02 December 2020. The Applicant claims priority to foreign application CN201911217202.0 filed 03 December 2019. An English translated copy of the foreign document has not been provided. Therefore, the effective filing date of the instant application is 02 December 2020.
Examiner’s Note
The Applicant's amendments and arguments filed 29 January 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 Rejections not reiterated from previous office actions are hereby withdrawn.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 29 January 2026, it is noted that claims 1 and 2 have been amended, claims 7-9 and 11-13 have been canceled, and no new claims have been added. Support for the amendments can be found on pg. 2 of the instant specification. No new matter has been added.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-27, 29, 32-39) in the reply filed on 08 May 2025 is acknowledged.
Claims 34-36, 40-44, 50-72 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species and invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08 May 2025 and 21 May 2025. It is noted that the Applicant did not fully respond to the restriction/election requirement, and only elected “species a (elemene)” instead of electing a species “for each of a-i.”
Declaration
The declaration under 37 CFR 1.132 filed 29 January 2026 is insufficient to overcome the rejection of claims 1-6, 10, 14-27, 29, 32, 33, 37-39 based upon the rejections by Chen, Karimi, and Choi as set forth in the last Office action because:
The Applicant submitted the processing steps for Example A (Declaration, pgs. 3-4). The unexpected results are not clearly defined but is presumed to be related to the safety assessment (Declaration, pg. 5).
Applicant’s argument is not found persuasive. Applicant’s results allegedly demonstrate that the lower dosages of samples resulted in better results compared to the higher concentrations or dosages. Karimi teaches that albumin, such as human serum albumin, are known in the art to have high stability (pg. 2). Furthermore, Chen teaches 2-10% sucrose (para. 137), 2-40% oil (para. 37), and 2-40% cryoprotectants, such as protein (para. 179), where Chen’s compositions solve the issue of providing stability and safety to elemene formulations (para. 31). Better safety and stability in the context of the prior art teachings is interpreted as also providing more favorable hemolysis values. Therefore, it is obvious that the claimed components in the claimed ratios would lead to better stability and safety.
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.
Claim(s) 1-6, 10, 14-20, 22-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen (US 20050186230 A1) and Karimi et al. (Albumin nanostructures as advanced drug delivery systems, Expert Opin Drug Deliv., 2016).
Chen teaches an injectable oil-in-water emulsion comprising beta-elemene and proteins, such as albumin (entire teaching, para. 33, 177), addressing claims 5 and 6. The size of the oil droplets, which is interpreted similarly to particles, may be less than 500 nm (para. 43), addressing claims 2-4, 24, and 25. The amount of elemene may be 0.5% and about 5% vegetable oil (claim 18), which may have a 5:1 ratio of oil to elemene, addressing claim 1. Vegetable oils include soybean oil (para. 68), which addresses the weight ratio in claim 1. The composition may be lyophilized and a cryoprotectant, such as sucrose, may be used (para. 167, 173), addressing claims 14-16. The composition may include antioxidants (para. 138), such as alpha-tocopherol (vitamin E), and glycerin (para. 171), as well as preservatives (para. 38), addressing claims 18, 19, and 22. The pH may be adjusted using HCl or NaOH (para. 193), addressing claim 20. Since Chen does not specify use of an organic solvent, it is interpreted as not required, addressing claim 23.
Chen does not specify using human albumin or teach an exact combination of components in claim 1. Chen does not teach specific ratios involving elemene, oils, protein, etc. in claims 10, 17, 26, 27, and 29.
Karimi et al. teach that albumin, such as human and bovine serum albumin, is favorably used in emulsion systems and nanoparticle structures to bind drugs and targeted drug delivery (entire teaching; pgs. 1, 2, 4). Albumin also favorably binds to lipophilic molecules, which is expected to include an oily compound such as elemene (instant specification, pg. 1).
In regards to selecting the combination of beta-elemene, soybean oil, albumin, “[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
combination 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.”
Chen teaches an injectable composition comprising beta elemene, soybean oil, and albumin, whereas the claimed invention is directed towards a composition comprising elemene, an oil for injection, and a protein carrier. Since Chen 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.
Since Chen does not specify using human serum albumin in claim 1, one of ordinary skill in the art would have been motivated to use the teaching from Karimi with a reasonable expectation of success. Chen teaches using albumin in their composition and Karimi teaches that human serum albumin has been used for targeted drug delivery and better binding abilities with lipophilic molecules in nanoparticle and emulsion systems.
In regards to the ratios of the components in claims 10 and 17, Chen teaches 2-10% sucrose (para. 137), 2-40% oil (para. 37), and 2-40% cryoprotectants, such as protein (para. 179). That being said and in lieu of objective evidence of unexpected results, the ratios can be viewed as a variable that achieves the recognized result of successfully making the elemene composition. The optimum or workable range of ratios 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 ratios as nonobvious.
Claim(s) 1-6, 10, 14-27, 29, 32, 33, 37-39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen (US 20050186230 A1), Karimi et al. (Albumin nanostructures as advanced drug delivery systems, Expert Opin Drug Deliv., 2016), and Choi et al. (WO 2014/003232 A1, machine citation).
In regards to claim(s) 1-6, 10, 14-20, 22-25, Chen and Karimi, as applied supra, is herein applied in its entirety for its teachings of an injectable composition comprising elemene.
Chen teaches a droplet size of less than 500 nm (para. 43), addressing claim 37.
Chen does not teach specific ratios for oil, elemene, human serum albumin, etc. in claims 26, 27, 29, 38, and 39. Chen does not specify solvents or sodium benzoate in claims 21, 32, and 33.
Choi teaches an emulsion solution (entire teaching; pg. 7, para. 6) that may comprise sodium benzoate (pg. 7, para. 6) and beta-elemene from Hwangchil trees (pg. 4, para. 6) in a solvent, such as methanol or ethanol (pg. 4, para. 9), addressing claims 21, 32, and 33. The formulation may be in the form of albumin injectable solutions (pg. 7, para. 6).
Since Chen does not specify solvents or sodium benzoate in claims 21, 32, and 33, one of ordinary skill in the art would have been motivated to use Choi’s teaching of an injectable solution comprising beta-elemene in a solution of methanol or ethanol to address the deficiencies in Chen’s teaching. Both Chen and Choi teach anticancer compositions (Choi, pg. 2, para. 5 and Chen, para. 11) from elemene. Chen and Choi also generally teach albumin solutions, where it would have been obvious to use Karimi’s teaching that human serum albumin is favorably used in emulsions and drug delivery systems. Therefore, a skilled artisan would have been motivated with a reasonable expectation of success to use Choi’s teaching of beta-elemene in solvents, as Chen does not specify use of solvents or teach against using them.
In regards to the ratios of the components in claims 26, 27, 29, 38, and 39, Chen teaches 2-10% sucrose (para. 137), 2-40% oil (para. 37), and 2-40% cryoprotectants, such as protein (para. 179). That being said and in lieu of objective evidence of unexpected results, the ratios can be viewed as a variable that achieves the recognized result of successfully making the elemene composition. The optimum or workable range of ratios 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 ratios as nonobvious.
Response to Arguments
Applicant's arguments filed 29 January 2026 have been fully considered but they are not persuasive.
The Applicant argues that the prior art is related to different technical features to solve different problems (Remarks, pg. 12).
Applicant’s argument is not found persuasive. Chen acknowledges safety issues already known in the art (para. 30) and teaches a composition and method to remedy stability and safety issues (para. 31). Additionally, Chen provides functionality and purpose for cryoprotectants, which are used to aid in emulsion droplets and the freeze-drying process (para. 169). Therefore, a skilled artisan would have been motivated to include cryoprotectants, such as albumin, in their composition.
In regards to Applicant’s argument that Chen does not disclose a single example using a cryoprotectant or albumin, 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 Chen does not teach human serum albumin in amended claim 1 (Remarks, pg. 12).
Applicant’s argument is not found persuasive. Karimi et al. teach that albumin, such as human and bovine serum albumin, is favorably used in emulsion systems and nanoparticle structures to bind drugs and targeted drug delivery (entire teaching; pgs. 1, 2, 4). Albumin also favorably binds to lipophilic molecules, which is expected to include an oily compound such as elemene (instant specification, pg. 1). Karimi also teaches that albumin, such as human serum albumin, are known in the art to have high stability (pg. 2).
Since Chen does not specify using human serum albumin in claim 1, one of ordinary skill in the art would have been motivated to use the teaching from Karimi with a reasonable expectation of success. Chen teaches using albumin in their composition and Karimi teaches that human serum albumin has been used for targeted drug delivery and better binding abilities with lipophilic molecules in nanoparticle and emulsion systems.
The Applicant argues that the unexpected results show that human serum albumin makes compositions have improved stability (Remarks, pg. 13).
Applicant’s argument is not found persuasive. Karimi teaches that albumin, such as human serum albumin, are known in the art to have high stability (pg. 2). Therefore, a composition comprising human serum albumin resulting in improved stability is not unexpected or surprising.
The Applicant argues that the data showing human serum albumin, elemene, and soybean oil in the claimed ratios show unexpected improved safety (Remarks, pgs. 13-14).
Applicant’s argument is not found persuasive. Karimi teaches that albumin, such as human serum albumin, are known in the art to have high stability (pg. 2). Furthermore, Chen teaches 2-10% sucrose (para. 137), 2-40% oil (para. 37), and 2-40% cryoprotectants, such as protein (para. 179), where Chen’s compositions solve the issue of providing stability and safety to elemene formulations (para. 31). Better safety and stability in the context of the prior art teachings is interpreted as also providing more favorable hemolysis values. Therefore, it is obvious that the claimed components in the claimed ratios would lead to better stability and safety.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
Prosecution Insights