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 3 February 2026 are acknowledged. Claims 1, 4, and 6-18 are currently pending. Claims 2-3 and 5 are cancelled. Claims 1, 4, 6-9, 12, and 14-15 are currently amended. Claims 1, 4, and 6-18 are examined on the merits within.
Terminal Disclaimer
2. The terminal disclaimer filed on 3 February 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application 18/188973 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Rejections
3. Applicants’ arguments, filed 3 February 2026, with respect to the obviousness double patenting rejection have been fully considered and are persuasive. The obviousness double patenting rejection of Application 18/188973 has been withdrawn in view of the approved Terminal Disclaimer.
New Rejections
Claim Rejections – 35 U.S.C. 112(b)
4. 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.
5. Claim 1 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.
6. Claim 1 recites the limitation "the glidant" in lines 12 and 13. There is insufficient antecedent basis for this limitation in the claim.
Modified Rejections
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, 4, and 6-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (U.S. Patent Application Publication No. 2018/0280392) in view of Yang et al. (CN106667952).
Zeng et al. teach 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazine-1-yl-pyridine-2-yl amino group)-8H-pyrido[2,3-d]pyrimidine-7-one (palbociclib) or salt thereof, the salt comprising isethionate in a dosage form having good stability and excellent dissolution performance. See abstract. The composition comprises at least one of disintegrant, diluent, binder, surfactant, and lubricant, wherein the active is present in amounts of 10-80%, disintegrant in amounts of 1-25%, diluent in amounts of 10-80%, lubricants in amounts of 0.1-5%, surfactants in amounts of 0-5% and binders in amounts of 0-20%. See claim 3. The composition is prepared by a dry granulation process. See claim 12. Example 4 comprises microcrystalline cellulose, lactose, hydroxypropyl cellulose, crospovidone, croscarmellose sodium and/or magnesium stearate. The dosage form is a capsule. See abstract.
Zeng et al. do not teach angle of repose and tap density.
Yang et al. teach a composition comprising palbociclib in amounts of 27-28.5%, lactose (diluent) in amounts of 21-22.5%, microcrystalline cellulose (diluent) in amounts of 42.5-44%, sodium carboxymethyl starch (disintegrating agent) in amounts of 4.5 to 5.5%, silicon dioxide (glidant) in amounts of 0.5 to 0.8%, and magnesium stearate (lubricant) in amounts of 1.2 to 2%. See abstract. Table 16 shows an angle of repose of 24.9 and 34.3 with a tap density of 0.858, 0.863, and 0.854. Yang et al. teach raw materials with poor fluidity and strong static electricity of palbociclib, to be successfully prepared by dry granulation to prepare uniform particles, which largely depends on mixing step before the dry granulation. See Experimental Example 6. Yang et al. teach filling capsules. See Examples 4 and 5.
It would have been obvious to one of ordinary skill in the art to modify the granulation process to control the angle of repose and tap density to increase fluidity resulting in more uniform particles. One would have been motivated, with a reasonable expectation of success to formulate a pharmaceutical composition which has good dissolution effect and a high dissolution rate, which is conducive to sufficient absorption and improves the efficacy as taught by Yang et al. See page 2. It would have been well within the purview of the skilled artisan to modify the order of steps, rate of reaction, and equipment used in the dry granulation process to achieve the optimal formulation with the desired properties since Yang et al. teach uniformity and fluidity are controlled by the order in which ingredients are combined.
Response to Arguments
Applicants’ arguments filed 3 February 2026 have been fully considered but they are not persuasive.
9. Applicants argued, “Zeng fails to discover the specific range of bulk density and tap density for palbociclib isethionate that provides a solution for good flowability suitable for commercial capsule filling. Zeng does not teach the capsules controlled the fill weight variation within 7.5%. Yang teach palbociclib tap densities and angle of repose for the free base form. The method of Yang is for the free base form. The prior art does not solve the problem of flowability for the isethionate form. Controlling the tap density and angle of repose as claimed achieves unexpected technical effects compared to solutions outside of this range. The present invention uncovers the relationship between weight variation/uniformity, tap density and angle of repose never mentioned in the prior art. This overcomes the lack of reproducibility of apparent parameters caused by different equipment models and shifts the timeframe for determining fill variation to the completion of granulation.”
In response to applicants’ arguments, the prior art of Yang was provided to make obvious the method steps. Yang teaches the importance of mixing prior to granulation. Yang teach raw materials with poor fluidity and strong static electricity of palbociclib, to be successfully prepared by dry granulation to prepare uniform particles, which largely depends on mixing step before the dry granulation. See Experimental Example 6. Thus mixing before granulation results in more uniform particles. Although Yang teaches the free base form, it would have been obvious to try this technique with the salt form with a reasonable expectation of success. Yang also teaches an angle of repose of 24.9 and 34.3 with a tap density of 0.858, 0.863, and 0.854. See Table 16. Thus the prior art teaches angle of repose values of less than 44, resulting in a need of only modifying the tap density. Yang teaches that the tap density of the bulk palbociclib material is 0.500 g/ml and angle of repose is 52.1. See Experimental Example 1. After the dry granulation process the tap density for three different particle sizes is 0.858, 0.863, and 0.854 with an angle of repose of 34.9, 34.9, and 34.3 respectively. See Table 16. Thus the processing techniques increased the tap density and decreased the angle of repose. In addition, Yang teaches the effect of the techniques on dissolution. See 4.1 Detection Method. Thus, it would have been obvious to apply the techniques of Yang to the salt taught by Zheng to control the uniformity, tap density, angle of repose, and dissolution properties of the compositions.
With regards to the unexpected technical effects, it is noted that the examples in specification are very specific with regards to types of excipients and amounts of each ingredient. However amounts of ingredients and types of excipients are not cited in claim 1. Thus the claim is not commensurate in scope with the data and it cannot be determined if processing steps alone result in the properties. Yang does show the importance of mixing before granulating to increase fluidity and uniformity and thus provides motivation to use the same processing steps. Therefore the results should be the same. Since the claims are not commensurate in scope with the data unexpected superiority cannot be determined.
In response to applicants’ argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., fill weight variation) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Thus this rejection is maintained.
Conclusion
10. 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
11. No claims are allowed at this time.
12. 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
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