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 .
Status of Claims
Claims 1, 3 and 7-23 are pending in the instant application. Claims 1, 3 and 7-23 are amended and claims 2 and 4-6 are cancelled via the amendment filed January 8th, 2026.
Priority
This is a 35 U.S.C. 371 National Stage filing of International Application No. PCT/EP2021/080054 filed October 28th, 2021, which claims priority under 35 U.S.C. 119(a-d) to BE20205878, filed December 3rd, 2020 and BE20205764, filed October 29th, 2020.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed 08/28/2025 and 12/31/2025 were considered by the Examiner.
Withdrawn Objections
Applicant’s arguments and amendments, filed January 8th, 2026, with respect to the objection of claim 1 have been fully considered and are persuasive. The objection of claim 1 has been withdrawn.
Applicant has overcome this object by amending claim 1 to replace “chosen from” in line 4 of the claim and insert “and” before “SO2R2” and replace “with” with “wherein” in lines 10-12 of the claim.
Applicant’s arguments and amendments, filed January 8th, 2026, with respect to the objection of claim 7 have been fully considered and are persuasive. The objection of claim 7 has been withdrawn.
Applicant has overcome this object by amending claim 1 to replace chosen from” with “selected from the group consisting of” and insert “and” before the last compound of the claim.
Withdrawn Rejections
Applicant’s arguments and amendments, filed January 8th, 2026, with respect to the rejection of claims 1, 3-4, 7-12 and 19-21 under 35 U.S.C 112(b) have been fully considered and are persuasive. The 35 U.S.C 112(b) rejection of claims 1, 3-4, 7-12 and 19-21 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to be directed towards a method.
Applicant’s arguments and amendments, filed January 8th, 2026, with respect to the rejection of claims 1, 4 and 9-23 under 35 U.S.C 103 have been fully considered and are persuasive. The 35 U.S.C 103 rejection of claims 1, 4 and 9-23 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to delete the recitation of R2 is H of the group NR2R3.
Applicant’s arguments and amendments, filed January 8th, 2026, with respect to the double patenting rejection of claims 1, 4, 7 and 9-23 under 35 U.S.C 103 have been fully considered and are persuasive. The 35 U.S.C 103 rejection of claims 1, 4, 7 and 9-23 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to be a method claim.
Response to Remarks
Applicant’s arguments regarding the claim objections, 112(b) rejection and double patenting rejection have been considered but are moot as Applicant’s amendments have overcome the objections and rejections.
Applicant’s amendments have overcome the previous 35 U.S.C. 103 rejection, however, as necessitated by amendment, a new grounds 103 rejection is presented below. Applicant’s amendments have necessitated changes to the previously presented rejections under 35 USC 103. Applicant’s arguments will be addressed as they relate to the rejection below, specifically Medina 2 (J. Med. Chem. 2009, 52, 7765-7777). Arguments related to Medina 1 (US 2016/0193233 A1) and Patani are considered moot as they are no longer used in the rejection, as necessitated by the amendment.
On p. 9 of the remarks, Applicant argues that Medina 2 compounds 18 and 19 are not analogues but prodrug-type compounds that are converted in situ to the DX101 compound.
However, the argument below, is based on the premise that the compounds of Medina are administered to cancer cells and Medina teaches compounds in which the hydroxy in the 3β position was functionalized, thus motivating one of ordinary skill in the art to alter said hydroxy of a known anticancer agent.
On p. 10 of the remarks, Applicant argues that the replacement of hydroxyl group in the 3β position is far from trivial and carrier a substantial risk of destroying anticancer activity.
In response, as mentioned above, Medina teaches compounds in which the functionalization of the hydroxy in the 3β position and that said functionalization of the hydroxyl in the C3 of the steroid backbone of dendrogenin A does not change the biological properties of dendrogenin A, the known anticancer agent.
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:
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.
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.
Claim(s) 1, 8-13 and 18-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Medina et al (Journal of Medicinal Chemistry, 2009 , Vol.52, No.23, as cited on the IDS dated 04/27/2023) in view of Brown et al (2012). Classical Bioisosteres. In Bioisosteres in Medicinal Chemistry).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Medina teaches the following compound (Table 1, compound 18):
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Medina further teaches that the compound above was administered to U-937 and P19 cells (page 7766, left column, paragraph 2). U-937 cells being myeloid leukemia cells and P19 cells being an embryonal carcinoma cell line.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The instant claims encompass a compound that differs from the prior art compound above by replacement of carbonyl with sulfone, i.e. where the sulfone group in the 3β position is a carbonyl group, corresponding to the compound of instant claim 8.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Medina teaches derivatives of the prior art compound above, in which the cabronyl in the 3β position is optionally functionalized for the treatment of cancer (Table 1, compounds 18-19). Medina teaches that the compounds in which the hydroxy in the 3β position was functionalized in the compound dendrogenin A, a known anticancer agent, were cytotoxic (page 7766, right column). Medina also teaches that the functionalization of the hydroxyl in the C3 of the steroid backbone of dendrogenin A did not change the biological properties of dendrogenin A (page 766, right column).
Further, Brown teaches that a bioisostere of the carbonyl group is the sulfone group (page 20).
Also, see MPEP 2144.09: See also In re Mayne, 104 F.3d 1339, 41 USPQ2d 1451 (Fed. Cir. 1997) (claimed protein was held to be obvious in light of structural similarities to the prior art, including known structural and functional similarity of the amino acids leucine and isoleucine); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (The tri-orthoester fuel compositions of the prior art and the claimed tetra-orthoester fuel compositions would have been expected to have similar properties based on close structural and chemical similarity between the orthoesters and the fact that both the prior art and applicant used the orthoesters as fuel additives.) (See MPEP § 2144 for a more detailed discussion of the facts in the Dillon case.).
Regarding claims 1 and 8, as such, one of ordinary skill in the art would have been motivated to replace the carbonyl group with a sulfone group in the compound taught by Medina and would have a reasonable expectation of success as Medina teaches the that functionalization of the 3β position of the compound dendrogenin A, a known anticancer agent, generally retains the same properties as dendrogenin A and Brown teaches that carbonyl and sulfone are bioisosteres and thus, the interchange of the groups is well known and has been successfully employed in the development of various pharmacological agents.
Regarding claims 9-10, as seen above, Medina teaches the administration of the compound to leukemia cells. Further, 50% of leukemia patients are chemo resistant, as evidenced by Aasebo et al (Cancers, 06/2020, 12, 1466). As half of leukemia patients are chemoresistant and the other half is chemo sensitive, one of ordinary skill in the art would recognize that as Medina teaches that the compound treats leukemia, this applies to both chemo resistant and chemo sensitive.
Regarding claims 11 and 19-20, as seen above, Medina teaches the administration of the above compound to subjects with leukemia, specifically, myeloid leukemia.
Regarding claim 12, daunorubicin is used in the treatment of leukemia, as evidenced by Löwenberg et al (n engl j med 361;13). As such, one of ordinary skill in the art would recognize that as the compound above is being administered to subjects with leukemia, that the subjects with be reistant to the drug used to treat leukemia, daunorubicin.
Regarding claims 13 and 23, as seen above, the method of treatment for shrinking a mammalian cancerous tumor is obvious over Medina and Brown. Further, Medina teaches that the compound above was tested in an aqueous solution (page 7775, right column, paragraph 5). Regarding the preamble of the instant claim “A pharmaceutical composition”, MPEP 2111.02(II) notes “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”. In this situation, the preamble is not considered limiting since it does not affect the structure of the compound or of the vehicle.
Regarding claim 18, as seen above, the composition is administered via any route.
Regarding claim 21, the compound is administered to leukemia cells and as the claims limitations are only to the type of lymphoma, the prior art reads on the claim.
Regarding claim 22, as Medina offers general teachings of the composition, one of ordinary skill in the art looking to optimize the method of Medina would have been motivated to screen options of administrations to arrive at the optimal method of treatment.
Claim(s) 1 and 8-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Medina et al (Journal of Medicinal Chemistry, 2009 , Vol.52, No.23, as cited on the IDS dated 04/27/2023) in view of Brown et al (2012). Classical Bioisosteres. In Bioisosteres in Medicinal Chemistry), as applied to claims 1, 8-13 and 18-23, and in further view of Weisberg et al (Leukemia. 2012 October ; 26(10): 2233–2244).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Neither Medina nor Brown teach that compound made obvious by the art above is administered with at least one other therapeutic agent. However, as seen above the method of administering a compound of formula (I) to shrink a mammalian a cancerous tumor, specifically a myeloid leukemia tumor has been rendered obvious.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
There is not a single embodiment wherein a compound of formula (I) is administered with at least one other therapeutic agent.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Weisberg teaches that PKC412 (midostaurin) is being used to treat myeloid leukemia (introduction, paragraph 2). Weisberg further teaches that the drug is being administered alone and in combination with daunorubicin (introduction).
As such, regarding claims 14-15, it would have been obvious to one of ordinary skill in the art to administer the compound of formula (I) with PKC412 (midostaurin) and daunorubicin.
See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Regarding claim 16, as seen in the 103 rejection above, daunorubicin is used in the treatment of leukemia, as evidenced by Löwenberg et al (n engl j med 361;13) and 50% of leukemia patients are chemoresistant.
Regarding claim 17, Weinsberg teaches that the chemotherapeutic agent, daunorubicin is administered in a high dose (introduction).
Conclusion
No claim is allowed. Claims 3 and 7 are objected to as being dependent on a rejected base claim.
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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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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