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
Status of Application
1. Applicants’ arguments/remarks filed 26 September 2025 are acknowledged. Claims 3, 5, 7-8, 10, 12, 15, 17-18, 20, 22, 25-28, 30-55 and 58-59 are cancelled. Claims 1-2, 4, 6, 9, 11, 13-14, 16, 19, 21, 23-24, 29, 56-57, and 60-72 are currently pending. Claims 62-72 are newly added. Claims 1-2, 4, 6, 9, 11, 13-14, 16, 19, 21, 23-24, 29, 57, and 60-61 are amended. Claims 1-2, 4, 6, 9, 11, 13-14, 16, 19, 21, 23-24, 29, 56-57, and 60-72 are examined on the merits within.
Withdrawn Objections/Rejections
2. Applicants’ arguments, filed 26 September 2025, with respect to the claim objections have been fully considered and are persuasive. The objection of claim 6 has been withdrawn. The 35 U.S.C. 102/103 Rejection over Moniz et al. (U.S. Patent Application Publication No. 2018/0093972) as evidenced by CDC has been withdrawn in view of the claim amendments. However, upon further consideration, a new rejection is made in view of Moniz et al. and Shailubhai et al.
Examiner’s Note: Claims 9, 11, 13, and 69-71 are free of the prior art.
New Rejections
Claim Rejections – 35 U.S.C. 112(b)
3. 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.
4. Claims 1-2, 4, 6, 9, 11, 13, 21, 23-24, 29, 56-57, and 60-72 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.
5. Claim 1 recites “an internal phase including an amount of a compound given by Formula 1.” There is no mention of external phase, thus it is unclear what “internal phase” is internal to. It appears the claim is lacking a component. Clarification is requested.
6. Claim 21 recites “wherein the capsule shell comprises by total weight of the capsule: 1.1 wt% of iron oxide red, 0.6 wt% of the titanium dioxide, and 98.3 wt% of the hypromellose.” It is unclear if these weights are for the entire product or the capsule shell. The claim states “by total weight of the capsule” but the values equate to 100% leaving no room for additional components, such as the compound of Formula 1, lactose monohydrate, calcium carbonate, etc. It is believed the weights are based on the total weight of the shell. Clarification is requested.
Claim Rejections – 35 U.S.C. 103
7. 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.
8. Claim(s) 1-2, 14, 16, 23-24, 29, 56-57, 64-68 and 72 is/are rejected under 35 U.S.C. 103 as being unpatentable over Moniz et al. (U.S. Patent Application Publication No. 2018/0093972) in view of Shailubhai et al. (U.S. Patent Application Publication No. 2009/0048175) as evidenced by CDC.
Moniz et al. teach compound 108:
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See paragraph [0009]. The compound may be provided in an acceptable oral dosage form such as capsules, tablets, aqueous suspensions or solutions including carriers such as lactose, corn starch, colloidal silica, cellulose based substances, and polyvinyl pyrrolidone and lubricating agents such as magnesium stearate or diluents (i.e. excipients). See paragraphs [0064 & 0068].
Moniz et al. teach free base or hydrochloride. See abstract.
Figures 1-4 show in vivo efficacy testing of compound 108 at doses of 25 mg/kg, 37.5 mg/kg, 12.5 mg/kg or 50 mg/kg. The average weight of a man is 90.6 kg and the average weight of a female is 77.5 kg. See CDC. This correlates to 1132.5 mg for 12.5 mg/kg up to 3397.5 mg for 37.5 mg/kg (for a male) and 968.75 mg for 12.5 mg/kg up to 2906.25 mg/kg (for a female).
Hepatocellular carcinoma has increased expression of FGFR4 and/or FGF19. See claim 25.
Although Moniz et al. teach lactose, corn starch, colloidal silica, cellulose based substances, polyvinyl pyrrolidone and magnesium stearate, Moniz et al. do not teach calcium carbonate, low substituted hydroxypropyl cellulose, lactose monohydrate, or copovidone.
Shailubhai et al. teach formulations used for treating cancer. See abstract. The composition can be in the form of a capsule. See paragraph [0017]. Excipients include polyvinyl pyrrolidone including copovidone, fillers such as calcium carbonate and talc, lactose monohydrate, low-substituted hydroxypropyl cellulose, magnesium stearate, and colloidal silicon dioxide. See paragraph [0116].
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to add calcium carbonate to the formulation of Muniz et al., as well as substitute copovidone for polyvinyl pyrrolidone, lactose monohydrate for lactose, and low substituted hydroxypropyl cellulose for cellulosed based substances because these are known effective excipients used in capsules administered for treating cancer. It would have been well within the purview of the skilled artisan to modify the amounts of ingredients to achieve the desired release profiles and pharmacokinetic parameters.
9. Claim(s) 4, 6, and 60-63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Moniz et al. (U.S. Patent Application Publication No. 2018/0093972) in view of Shailubhai et al. (U.S. Patent Application Publication No. 2009/0048175) as applied to claims 1-2, 14, 16, 23-24, 29, 56-57, 64-68 and 72 above and further in view of Rioux et al. (Cancer Chemotherapy and Pharmacology, 2019) as evidenced by CDC.
Moniz et al. and Shailubhai et al. do not teach 500 mg to 700 mg, fasted or fed.
Rioux et al. teach 200 mg capsules of H3B-6527 (same as compound 108 and the instantly claimed compound) for a food effect study. See page 92. Figure 1 shows the difference in plasma concentration over time when administered H3B-6527 under fasted versus fed conditions. The results show that under both fasted and fed conditions the capsule was safe and well tolerated. There was approximately a 2-h delay in tmax following a meal showing that food slowed absorption, although duration of absorption was extended. See page 95.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the amount of active ingredient to achieve the desired effect because both Moniz et al. and Rioux et al. teach varying amounts of compound shown to be effective in values as low as 200 mg up to 3400 mg. It would have been obvious to administer the drug in fasted or fed state dependent on the desired need of the patient because Rioux et al. teach that both fasted and fed are efficacious, however a meal slows the absorption time.
10. Claim(s) 19 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Moniz et al. (U.S. Patent Application Publication No. 2018/0093972) in view of Shailubhai et al. (U.S. Patent Application Publication No. 2009/0048175) as applied to claims 1-2, 14, 16, 23-24, 29, 56-57, 64-68 and 72 above and further in view of Siegel et al. (U.S. Patent Application Publication No. 2011/0171201) as evidenced by CDC.
Moniz et al. and Shailubhai et al. do not teach red iron oxide, hypromellose and titanium dioxide in the capsule shell.
Siegel et al. teach active ingredients can be encapsulated in gelatin or hypromellose capsules. Agents can be added to improve color, taste, stability, buffering capacity, dispersion or other known desirable features such as red iron oxide and titanium dioxide. See paragraph [0056].
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to use various known effective materials such as hypromellose, titanium dioxide and red iron oxide to formulate a suitable capsule. It would have been well within the purview of the skilled artisan to modify the amount of each ingredient to achieve desirable color, taste, stability, etc.
Response to Arguments
Applicants’ arguments filed 26 September 2025 have been fully considered but they are not persuasive.
11. Applicants argued, “Moniz and Rioux do not disclose the claimed features and therefore cannot inherently produce the surprising pharmacokinetic results without some factual evidence.”
In response to applicants’ arguments, the rejection has been modified to include the prior art of Shailubhai et al. to make obvious the additional components. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to add calcium carbonate to the formulation of Muniz et al., as well as substitute copovidone for polyvinyl pyrrolidone, lactose monohydrate for lactose, and low substituted hydroxypropyl cellulose for cellulose based substances because these are known effective excipients used in capsules administered for treating cancer. It would have been well within the purview of the skilled artisan to modify the amounts of ingredients to achieve the desired release profiles and pharmacokinetic parameters.
Conclusion
12. Applicants’ 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.
Correspondence
13. No claims are allowed at this time.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615