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 .
Response to Arguments
Applicants’ claim amendments and Remarks of 7/21/2026 are acknowledged and have been considered.
Any rejection and/or objection not specifically addressed or modified below is herein withdrawn.
In regard to the anticipatory rejection, this rejection is withdrawn due to applicant’s claim amendments.
In regard to the 103 rejection, this rejection is maintained. Applicants Remarks with Examiner’s reply are summarized below:
Applicants submit that there is no articulated reason that the combination would have been predictable or reasonably expected to succeed.
Examiner disagrees. Both compounds are known to have anti-liposarcoma properties. Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Perez teaches that palbociclib activity is conditional and tumor-specific (effective against tumors with high CDK4 levels).
It is obvious to administer a treatment (palbociclib) to any patient who has liposarcoma, including a sub-population that has high CDK4 levels, because nothing precludes them from the treatment.
Mahmood does not demonstrate meaningful tumor shrinkage in liposarcoma.
Some tumor shrinkage (compared to meaningful tumor shrinkage) still teaches the usefulness of sunitinib treating liposarcoma.
Applicants submit that the combination would introduce unresolved safety, dosing, and interaction questions.
This introduces enablement issues and is not persuasive in overcoming an obviousness rejection.
Applicants point out that palbociclib and sunitinib produced synergistic inhibition of tumor growth.
Examiner reviewed examples and does not find there are synergy for the full scope of base claims 1, 21, and 43. Applicants show (below) that the palbociclib and sunitinib combination had synergistic inhibition for some cancers below.
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A review of these examples showed dosages for palbociclib and sunitinib between 20-250 mg/day and 10-125 mg/day respectively. Also, Applicants further state that other combinations (such as palbociclib and sorafenib of the instant claim’s 1, 21, and 43) only had additive effects in some cancer models. Additionally, palbociclib and sunitinib were found to be less effective than sunitinib alone in the appendix carcinoma model. Additionally, there is no comparison to a liposarcoma model.
Though Applicant states that unexpected results have been achieved, the instant specification does not provide any unexpected or surprising results (especially in view of the full scope of “solid cancer” and since any dosage can be used). The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See MPEP 716.01(c).
MPEP 716.02 states that unexpected results a) are greater than expected results, b) show superiority of a property shared with the prior art, c) exhibit the presence of an unexpected property, and/or d) exhibit the absence of an expected property. MPEP 716.02 additionally states that unexpected results must be commensurate in scope with the claimed invention and provide a comparison with the closest prior art.
As Applicants are arguing that these anti-cancer combinations are highly unpredictable, this introduces enablement issues and is not persuasive in overcoming an obviousness rejection.
Examiner recommends narrowing the “solid cancers” and possibly the dosage amounts in order to overcome the obviousness rejection and avoid future enablement issues.
In regard to the double patenting rejection for application 18/975,802, this rejection is withdrawn as Applicants have submitted a terminal disclaimed.
Response to Amendment
Claim Objections
Claim 21 is objected to because of the following informalities: “suitinib” should be sunitinib. Appropriate correction is required.
Claim Rejections - 35 USC § 103- Maintained
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:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 2, 4, 7, 9, 21-23 and 43, 44, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over PEREZ (Perez et al., “Efficacy of CDK4 inhibition against sarcomas depends on their levels of CDK4 and p16ink4 mRNA”, Oncotarget, October 20, 2015), as evidenced by FDA ( “IBRANCE® (palbociclib) tablets, for oral use”, FDA, Reference ID: 4514390, initial approval 2015, Revised 2019) and in view of MAHMOOD (Mahmood et al., “Phase II Study of Sunitinib Malate, a Multi-Targeted Tyrosine Kinase Inhibitor in Patients with Relapsed or Refractory Soft Tissue Sarcomas. Focus on 3 Prevalent Histologies: Leiomyosarcoma, Liposarcoma, and Malignant Fibrous Histiocytoma”, Int J Cancer, October 15, 2011).
PEREZ teaches that palbociclib (PD0332991), a highly selective inhibitor of CDK4/6, being used to treat sarcoma in vivo (abstract). This helps teach claim 1, 2, 4, 43, and 44 (i).
PEREZ teaches palbociclib is useful in treating Liposarcoma cell line (table 1). This helps teach claims 7 and 45.
PEREZ teaches the drug (Palbociclib, PD0332991), was obtained from Pfizer, freshly prepared and orally administered (In vivo treatments). PEREZ teaches the concentration used in human is 125mg/dose (In vivo treatments). This helps teach limitation (i) from claim 9 and 23.
FDA is relied upon for the beneficial teaching that the oral dosage of palbociclib contains the inactive ingredients including microcrystalline cellulose (page 14). These inactive ingredients are pharmaceutically acceptable excipients. This helps teach claim 21.
While PEREZ teaches Palbociclib, PEREZ does not teach Sunitinib.
MAHMOOD teaches that Sunitinib is useful for treating liposarcoma (table 3). This helps teach claim 1, 2, 4, 43, and 44 (i). This helps teach claims 7 and 45.
MAHMOOD teaches Patients received 50 mg of sunitinib malate orally once daily on days 1-28 of a planned 42-day cycle (study design). This helps teach limitation (i) from claim 9 and 23.
The artisan would have found it obvious to combine Palbociclib and sunitinib, which are known to have anti-liposarcoma properties (PEREZ abstract; MAHMOOD abstract). It is prima facie obvious to combine one anti- liposarcoma compound with another in order to form a composition to be used for the very same purpose (treating liposarcoma). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06(I). This teaches 1, 2, 4, 7, 9, 43, 44, and 45.
The artisan would have also found it obvious to administer a pharmaceutical composition containing a pharmaceutically acceptable excipient. Combining Palbociclib with sunitinib, the artisan would have at least kept the excipient (microcrystalline cellulose) from Pfizer’s palbociclib (FDA page 14). This teaches claims 21-23.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
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/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
