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
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed January 6, 2026. The amendment, filed January 6, 2026, is entered, wherein claims 1 – 3 and 6 – 9 are amended and claims 13 – 16 are new.
Claims 1 – 16 are pending in this application and are currently examined.
Priority
This application is a national stage application of PCT/IB2020/050651, filed January 28, 2020, which claims benefit of foreign priority document ZA2019/00623, filed January 30, 2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Rejections
4. The rejection of claims 1 – 4, 6 – 8, and 10 – 11 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Palma et al. has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 5 and 11 – 12 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 103 as being unpatentable over Guerra et al. in view of Yamaguchi et al. has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 6 – 9 and 10 in the previous Office Action, mailed August 6, 2025, under 35 U.S.C. 103 as being unpatentable over Guerra et al. in view of Yamaguchi et al. as applied to claims 1 – 5 and 10 – 12 above, and further in view of Chang et al. has been considered and is withdraw in view of the amended claim 1.
The rejection of claims 1 – 12 in the previous Office Action, mailed August 6, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 10 – 18 and 28 – 29 of copending Application No. 18/996,685 in view of Guerra et al. and Yamaguchi et al. has been considered and is withdrawn in view of the amended claims 1 and 2.
The following are new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed January 6, 2026, wherein claims 1 – 3 and 6 – 9 are amended and claims 13 – 16 are new. Previously and newly cited references have been used to establish the new grounds of rejection.
New 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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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.
Claims 1 – 16 are rejected under 35 U.S.C. 103 as being unpatentable over Badana et al. (Journal of Breast Cancer, 2016, Vol. 19, Issue 4, Reference included with PTO-892) in view of Alawin et al. (The Journal of Nutritional Biochemistry, 2016, Vol. 27, Issue 2016, page 266 – 277, Reference included with PTO-892) and Yamaguchi et al. (FEBS Letters, 2015, Vol. 589, page 4097 – 4105, cited in the previous Office Action).
a. Regarding claims 1 and 12 – 13, Badana et al. disclose that lipid raft integrity is required for survival of triple negative breast cancer cells (Title). Badana et al. found in the study that the cholesterol-depleting agent, MβCD, efficiently depletes membrane cholesterol and causes concentration dependent (0.1 – 0.5 mM) cytotoxicity compared to nystatin and filipin III in TNBC cell lines. MβCD also causes cell cycle arrest at the G2M phase and apoptosis in MDA-MB 231 cells and in MDA-MB 468 cells. Badana et al. conclude that MβCD-induced cholesterol removal enhances alterations in lipid raft integrity, which reduces TNBC cell survival (Abstract).
However, Badana et al. do not teach the use of 2-hydroxypropyl-β-cyclodextrin (HPβCD). Badana et al. do not explicitly teach that the amount of HPβCD is not toxic to the subject.
Alawin et al. teach that hydroxypropyl-β-cyclodextrin (HPβCD) is an agent that disrupts lipid raft integrity.
Yamaguchi et al. disclose that beta-cyclodextrin (bCD) and its derivatives for targeting cholesterol would disrupt signal transduction between PI3K and AKT and would attenuate AKT pro-survival signals (Abstract). bCD would sensitize cancer cells for apoptosis (Title). Yamaguchi et al. also disclose that HPβCD is found safe to use because the exposure time is less than 3 hours for both cell and animal experiments (page 4102, Left Col., para. 1). Furthermore, when administered orally, absorption of HPβCD is better than that of MbCD (page 4100, Right Col., para. 2). Other studies have shown that HPβCD may be injected into mice (page 4098, Right Col., para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute MβCD for the treatment of TNBC as taught by Badana et al. with HPβCD in view of Alawin et al. because Badana et al. teach that cholesterol depletion by MβCD disrupts lipid raft integrity, which is associated with induction of G2M phase cell cycle arrest and apoptosis in TNBC cells and Alawin et al. teach that HPβCD will disrupts lipid raft integrity. One would have been motivated to substitute MβCD for the treatment of TNBC as taught by Badana et al. with HPβCD in view of Alawin et al. because Alawin et al. teach that HPβCD similarly disrupts lipid raft integrity, thereby providing a predictable alternative cholesterol-depleting agent for producing the same lipid raft disruption and associated anticancer effects. For “the amount is not toxic to the subject”, Yamaguchi et al. disclose that HPβCD was found safe to use in cell and animal experiments. It is expected that HPβCD is administered at a dose or exposure level that does not produce unacceptable toxicity. Therefore, Yamaguchi et al. suggest administration of HPβCD at a tolerable, non-toxic amount. It would have been obvious to a person of ordinary skill in the art to select an amount of HPβCD that is effective for treating TNBC while not toxic to the subject because optimization of dose to balance therapeutic efficiency and safety is a routine practice in the art. Yamaguchi et al. also teach that HPβCD may be administered orally or by injection. One of ordinary skill in the art would have understood that such oral or injection formulations are known in the art to contain one or more excipients for the purpose of delivery or administration of the composition. For the selection of subject with the recited tumor size, the combination of Badana et al., Alawin et al., and Yamaguchi et al. does not indicate the disclosed treatment is only restricted to a specific tumor size. A person of ordinary skill in the art would have found it obvious to administer HPβCD to subjects having TNBC tumors across a range of tumor sizes, including tumor greater than 20 mm3. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success to substitute MβCD for the treatment of TNBC as taught by Badana et al. with HPβCD in view of Alawin et al. because Badana et al. teach the working mechanism of cholesterol depleting agent in treating TNBC and Alawin et al. teach that HPβCD disrupts lipid raft integrity, thereby suggesting that HPβCD would function similarly to MβCD in producing lipid raft disruption and associated anticancer effects.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed January 6, 2026, have been fully considered and are found to be not persuasive.
Regarding Guerro et al., Applicant argues that Guerro et al. only consider the invasion and migration of cancer cells and a teaching that HPβCD is effective to inhibit the migration of breast cancer cells does not imply a therapeutic effect of HPβCD on TNBC. Regarding Yamaguchi et al., Applicant argues that Yamaguchi et al. cannot supplement the deficiencies in Guerro et al. and that Yamaguchi et al. teach a combination therapy of 2DG-bCD-ADT. A person of skill in the art would not have been motivated to substitute MβCD with HPβCD as the only active pharmaceutical ingredient in view of Yamaguchi et al. Applicant also argues that Yamaguchi et al. teach away from HPβCD because Yamaguchi et al. teach that the same negative side effects are not observed when using only a combination of 2DG-ABT. Furthermore, Applicant argues that Yamaguchi et al. teach that HPβCD alone does not appear to be effective in hindering tumor volume enlargement. However, these arguments are moot because the previous rejections over Guerro et al. in view of Yamaguchi et al. have been withdrawn. The new rejection is relied upon the combination of Badana et al., Alawin et al., and Yamaguchi et al. Badana et al. teach that working mechanism of cholesterol depleting agent in treating TNBC, which is disrupting lipid raft integrity to reduce TNBC cell survival, Alawin et al. teach that HPβCD disrupts lipid raft integrity, and Yamaguchi et al. teach the administration routes of HPβCD. The combination of these references renders the claimed invention obvious.
Conclusion
No claim is found to be allowable.
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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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693