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 .
Applicant canceled Claims 1-10, 14, 16 and 17.
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.
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.
The following 112(b) rejection was made in the last Office Action but was not addressed properly in applicant’s reply filed on February 10, 2026 (although applicant state in their REMARKS they have canceled claim 15, claim 15 was not canceled).
Claim 15 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 15, the phrase "such as" (on line 2) 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
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.2
Claim(s) 11-13, 15 and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over SIEMEISTER (WO 2018/206547 A1) in view of FINNIE et al (US 2019/0111057 A1) and YANG (US 2021/0000746 A1).
Siemeister teaches (abstract, pg.1 lines 1-10, pg.81, lines 27-34) combinations of at least two components, component A (an inhibitor of Bub 1 kinase) and component B (an ATR inhibitor) for the treatment of or prophylaxis of a cancer, such as non-small cell lung cancer. Siemeister specifically teaches (pg.41, line 5, pg.104, lines 1-9) AZD6738 (instant ceralasertib – see present specification, pg.3, lines 25-30) as its component B.
Siemeister further teaches (pg.4, lines 10-25, claim 19) a kit comprising a combination of component A, component B and optionally, component C (one or more further pharmaceutical agents), in which optionally both or either of the components A and B are in the form of a pharmaceutical formulation/composition which is ready for use to be administered simultaneously, concurrently, separately or sequentially. Siemeister further teaches (pg.21, lines 1-15, claims 20-22) that components A, B and C can be present in different and separate pharmaceutical formulations. Furthermore, Siemeister teaches (pg.71, line 1) that the components of its invention can be tableted with conventional tablet bases and gives as an example tablet formulation on pg.80 (lines 15-20) containing: active ingredient, colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, starch and lactose. Based on Siemeister’s teaching, it would be obvious to one skilled in the art to form a tablet formulation containing AZD6738 (ceralasertib) as the active ingredient together with colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, starch and lactose with a reasonable expectation of success. As to instant dibasic calcium phosphate, Siemeister teaches the equivalence of lactose and dibasic calcium phosphate as tablet diluents (pg.78, lines 12-15). Thus, it would be obvious to one skilled in the art to replace the lactose in Siemeister’s tablet formulation (containing AZD6738 as the active ingredient) with dibasic calcium phosphate with a reasonable expectation of success.
Siemeister does not teach instant low-substituted hydroxypropyl cellulose. However, as evidenced by Finnie ([0083], abstract and [0220]), it is known in the art that starch and low-substituted hydroxypropyl cellulose are equivalent as disintegrants used in tablet formulations for the treatment of non-small cell lung cancer. It would be obvious to one skilled in the art to use low-substituted hydroxypropyl cellulose instead of starch in Siemeister’s tablet formulation (containing AZD6738) with a reasonable expectation of success.
Thus, Siemeister in view of Finnie renders obvious instant pharmaceutical formulation comprising ceralasertib, anhydrous dibasic calcium phosphate, microcrystalline cellulose, low substituted hydroxypropyl cellulose and magnesium stearate.
With respect to instant amount 40 wt.% for ceralasertib, Siemeister’s example tablet formulation (pg.80, lines 15-20) discussed above contains 100 mg of active ingredient (such as AZD6738), which gives 20.4 wt.% (as calculated by the Examiner). However, since Siemeister teaches (pg.90, lines 31-32) that a unit dosage for its component (B) (such as AZD6738) can contain 0.5-1500 mg of the active ingredient, this means that Siemeister’s tablet formulation can contain 0.13 wt.% to 79 wt.% (as calculated by the Examiner) of the active ingredient (AZD6738). Under such general guideline provided by Siemeister, instant amount (40 wt.%) for ceralasertib as claimed in claim 11 would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
With respect to instant amount 15 wt.% for the anhydrous dibasic calcium phosphate and instant amount 33.5 wt.% for the microcrystalline cellulose, microcrystalline cellulose and anhydrous dibasic calcium phosphate are being used as tablet diluents in Siemeister (see pg.78, lines 12-15). Although Siemeister does not explicitly teach instant amounts for the anhydrous dibasic calcium phosphate and microcrystalline cellulose, as evidenced by YANG ([0108]-[0109]), it is well known in the art that fillers or diluents (such as dibasic calcium phosphate anhydrous or microcrystalline cellulose) can be used in the amount that ranges anywhere from about 5 to 95 wt.% in the solid core of a tablet. Under such general guideline known in the art, instant amounts for the anhydrous dibasic calcium phosphate (15 wt.%) and microcrystalline cellulose (33.5 wt.%) would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, supra.
With respect to instant amount 10 wt.% for the low substituted hydroxypropyl cellulose, although Siemeister in view of Finnie does not teach instant amount for the low-substituted hydroxypropyl cellulose, as evidenced by YANG ([0110]-[0111]), it is well known in the art that disintegrants (such as L-hydroxypropyl cellulose) can be used in the amount that ranges from about 10 to 90 wt.% of the solid core of a tablet. Under such general guideline given by Yang, instant amount (10 wt.%) for the low-substituted hydroxypropyl cellulose would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, supra.
With respect to instant amount 1.5 wt.% for the magnesium stearate, in Siemeister’s tablet formulation discussed above, magnesium stearate is present in the amount of 1.02 wt.% which does not teach instant amount for the magnesium stearate. However, as evidenced by YANG ([0114]-[0115]), it is well known in the art that lubricants (such as magnesium stearate) can be used in the amount that ranges from about 0.1 to 5 wt.% of the solid core of a tablet. Under such general guideline given by Yang, instant amount (1.5 wt.%) for the magnesium stearate would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, supra.
Thus, Siemeister in view of Finnie and Yang renders obvious instant claims 11, 12, 18 and 19 (with respect to instant claim 18, Siemeister states (pg.1, lines 19-21) that a therapeutically effective amount of the combination (containing component (B)) is administered to a subject).
With respect to instant claim 13, Siemeister teaches (pg.80, lines 18-19) that appropriate coatings may be applied to its tablets to increase palatability or improve elegance. Finnie teaches ([0195]) that a colorant may be used as part of a tablet coating. It would be obvious to one skilled in the art to apply a colored coating to Siemeister’s tablet so as to increase palatability and improve elegance. Thus, Siemeister in view of Finnie and Yang renders obvious instant claim 13.
With respect to instant claim 15, Siemeister teaches (pg.81, lines 5-8) that component B (such as AZD6738) is suitable to have effects on tumor diseases because they inhibit ATR. Thus, when the tablet formulation containing AZD6738 (as modified by the teachings of Finnie and Yang) is taken by a patient, it would naturally produce an ATR inhibitory effect. Thus, Siemeister in view of Finnie and Yang renders obvious instant claim 15.
With respect to instant claim 20, Siemeister teaches (pg.20, lines 1-3) that its invention includes all possible crystalline forms or polymorphs of the compounds used in the combination of its invention. Thus, it is the Examiner’s position that instant ceralasertib Form A (as described in instant claim 20) would naturally be encompassed by Siemeister’s component B, AZD6738. Thus, Siemeister in view of Finnie and Yang renders obvious instant claim 20.
With respect to instant claims 21-23, Siemeister does not teach instant amounts of active ingredient (such as AZD6738 (ceralasertib)) in its tablet formulation discussed above. However, as already discussed above, Siemeister teaches (pg.90, line 12, lines 31-33) that a unit dosage for its component (B) may contain from about 0.5 mg to about 1500 mg of active ingredient (i.e., component B). Under such general guideline given by Siemeister, instant amounts of ceralasertib as claimed in claims 21-23 would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, supra. Thus, Siemeister in view of Finnie and Yang renders obvious instant claims 21-23.
Response to Arguments
With respect to the pending 103 rejection, applicant argue that Siemeister or Finnie does not teach or suggest instant formulation, which requires 40% w/w, which is a high drug load of ceralasertib. Applicant also argue that neither Siemeister nor Finnie suggests a link between excipient selection with the result of achieving desired tensile strength and porosity, which minimizes over- compression risks and dissolution variability. Applicant argue that achieving this high drug load of 40% w/w of ceralasertib while maintaining robust mechanical integrity and dissolution performance involves interdependent, API specific behaviors. Applicant further argue that the claimed ratios (amounts) produce non-obvious results (target tensile strength at lower compression force and porosity greater than 10%) that are neither disclosed nor suggested for ceralasertib by the cited art. Applicant argue that even if a skilled person could select excipients from the disclosed classes and ranges, there is no teaching to arrive at these precise ratios for ceralasertib or a reasonable expectation of success in obtaining the combined performance outcomes through routine optimization and argue that not only do range disclosures fail to make every point within those ranges obvious but also the cited art fail to demonstrate how to predict the link between the exact ratios and the combined performance advantages. Applicant argue that as the instant formulation of 40% w/w ceralasertib is a high drug load, the amounts and ratios of excipients used for an effective formulation does not necessarily fall under the general guidelines as described in Yang since Yang does not provide guidance for high drug load formulations. Applicant thus argue that Yang does not provide for one skilled in the art to arrive at the instant amounts and ratios of excipients for a successful and effective tablet formulation.
The Examiner disagrees. (i) For the reasons already explained above, it is still the Examiner’s position that Siemeister in view of Finnie does render obvious instant pharmaceutical formulation comprising ceralasertib, anhydrous dibasic calcium phosphate, microcrystalline cellulose, low substituted hydroxypropyl cellulose and magnesium stearate. Although applicant argue that neither Siemeister nor Finnie suggests a link between excipient selection with the result of achieving desired tensile strength and porosity, which minimizes over-compression risks and dissolution variability, the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."). See MPEP 2144 (IV). (ii) As to the claimed amounts for each of the components: as already explained above, Siemeister teaches that a unit dosage for the component (B) (such as AZD6738 (ceralasertib)) can contain 0.5-1500 mg of the active ingredient, which means that Siemeister’s tablet formulation can contain 0.13 wt.% to 79 wt.% of the active ingredient (such as ceralasertib); although Siemeister does not explicitly teach instant amounts for the anhydrous dibasic calcium phosphate and microcrystalline cellulose, as evidenced by YANG, it is well known in the art that fillers or diluents (such as dibasic calcium phosphate anhydrous or microcrystalline cellulose) can be used in the amount that ranges anywhere from about 5 to 95 wt.% in the solid core of a tablet; although Siemeister in view of Finnie does not teach instant amount for the low-substituted hydroxypropyl cellulose, as evidenced by YANG, it is well known in the art that disintegrants (such as L-hydroxypropyl cellulose) can be used in the amount that ranges from about 10 to 90 wt.% of the solid core of a tablet; and although Siemeister’s example tablet formulation discussed above contains magnesium stearate in the amount of 1.02 wt.%, as evidenced by YANG, it is well known in the art that lubricants (such as magnesium stearate) can be used in the amount that ranges from about 0.1 to 5 wt.% of the solid core of a tablet. Under these general guidelines provided by the cited prior arts, it is still the Examiner’s position that the claimed amounts for instant components would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, at 456. The proposition, which In re Aller stands for, may be rebutted by objective evidence of unexpected results. See also MPEP 2144.05 (II)(A), which states that generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05 (II)(A). (iii) Comparative data shown in Table 5 of present specification were carefully considered by the Examiner but were found to be unsuccessful in showing unexpected superior results of instant invention for the following reasons: Applicant’s invention of claim 11 is represented by the formulation N11 shown in Table 5. In order to fairly show unexpected superior results of using instant formulation (N11), applicant need to compare the formulation N11 directly to a comparative formulation using 40 wt.% of ceralasertib, 15 wt.% of mannitol (instead of 15 wt.% of DCPA), 33.5 wt.% of MCC, 10 wt.% of SSG (instead of 10 wt.% of LHPC), 0.5 wt.% of magnesium stearate (intra) and 1 wt.% of magnesium stearate (extra) (by keeping the amounts for the corresponding components the same between the formulation N11 and the comparative formulation, one would be able to ascertain whether the unexpected superior properties of N11 come from choosing the claimed components). However, there is no such comparative formulation shown in N2-N10. Also, if applicant want to show unexpected superior results of using the claimed amounts for each of the components, applicant need to compare the formulation N11 to several comparative formulations containing the same claimed components (i.e., ceralasertib, anhydrous dibasic calcium phosphate, microcrystalline cellulose, low substituted hydroxypropyl cellulose and magnesium stearate) but in amounts different from those claimed amounts. However, no such comparative formulations were presented in Table 5.
For the reasons stated above, instant 103 rejection over Siemeister in view of Finnie and Yang still stands.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SIN J. LEE whose telephone number is (571)272-1333. The examiner can normally be reached on M-F 9 am-5:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached on 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SIN J LEE/
Primary Examiner, Art Unit 1613
March 13, 2026