DETAILED ACTION
A non-final Office action was mailed 4 September 2025 (“Office Action”).
Applicant’s reply to the Office Action was received 2 December 2025 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 1, 16, 17, 23, 29–31, 33, 35, 36, 39, 40, 50, and 51 are pending.
Claims 2–15, 18–22, 24–28, 32, 34, 37, 38, and 41–49 are canceled.
Claims 1 and 16 are amended.
Claims 50 and 51 are new.
Status of Rejections and Objections
The text of those sections of Title 35, U.S. Code and/or text providing the basis for non-statutory double patenting rejections not included in this action are set forth in the Office Action.
Unless repeated herein, any objection or rejection in the Office Action is withdrawn.
Objections to the Specification
The title of the invention is objected to because it refers to the purported merits of the invention (“Novel”).
Appropriate correction is required.
For guidelines for the preparation of patent titles, see MPEP § 606 (Explaining: The word novel should not be included in the title of the invention).
Claim Objections
Claims 50 and 51 are objected to for using improper underlining.
Any claim added by amendment must be presented in clean version, i.e., without any underlining. 37 C.F.R. § 1.121(c)(3).
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 103
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.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claims 1, 16, 17, 50, and 51 are rejected under 35 U.S.C. § 103 as being unpatentable over WO2015/161032 (“Wang”) [IDS] in view of admissions provided in the instant specification (“Spec.”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Wang teaches a method of treating a disease such as cancer with an inhibitor of MDM2 and MDM2-related proteins. (Wang, Abstract; claims 27–29).
The MDM2 inhibitor is a compound of formula (I) and the particular compounds of formula (I). (Id., p.3; p.7 (Scheme II, Ex. No. 8); p.53 (Ex. No. 8); p.56 (Table 2, Ex. No.8); claims 1, 24).
The cancer can be leukemia, such as acute lymphocytic leukemia (ALL) in adults, acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and chronic myelomonocytic leukemia (CMML). (Id., ¶¶26; 53; 136).
The MDM2 inhibitor compound can be administered orally at a dose of 0.0025 to 50 mg/kg, or about 0.01 to about 25 mg/kg, per day of the body weight of the mammal. (Id., ¶163).
“Dosage amounts and intervals can be adjusted individually to provide plasma levels of the MDM2 inhibitor that are sufficient to maintain the desired therapeutic effects.” (Id., ¶162). For example, one dose can be delivered per day at five-day intervals. (Id.).
The amount of MDM2 inhibitor used in the claimed method can be obtained via routine experimentation by one of ordinary skill in the art. (Spec, ¶231: “One skilled in the art would be able, by routine experimentation, to determine what an effective, non-toxic amount of a MDM2 inhibitor (e.g., Compound C) would be for the purpose of treating cancers.”).
Ascertaining the differences between the prior art and the claims at issue
Wang does not teach treating T-cell prolymphocytic leukemia (T-PLL) by administering Ex. No. 8 (i.e., Compound C of the instant application).
Wang does not mention a “28-day treatment cycle,” as recited in claim 17.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application does not include evidence of unexpected results or significantly improved properties compared to other MDM2 inhibitors. The examples appear to be prophetic (stating: “Blood samples will be collected.”; “The treatment response of the patients will be assessed at the end of each cycle.”). (Spec., ¶¶213; 216; 219)(emphasis added).
The question of obviousness
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to administer, with an expectation of success, Wang Ex. No. 8 (corresponding to Compound C in the instant application) to a subject in need of treatment for T-PLL because Wang teaches a method of administering the same compound to treat diverse types of leukemia via the inhibition of MDM2 and MDM2-related proteins.
One of ordinary skill in the art would have been motivated to modify Wang by administering Ex. No. 8 to a subject in need of treatment for T-PLL because T-PLL is a subtype of lymphocytic leukemia and there are a limited number of leukemia subtypes.
Wang appears to disclose the general dosage and regimen elements in claims 16, 17, 50, and 51; however, to the extent a specific feature is not disclosed, Applicant acknowledged that such features could be ascertained through routine experimentation. See, e.g., In re Aller, 220 F.2d 454, 456 (CCPA 1955) (“[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.”). Further, there is no evidence of criticality for the claimed dosage and regimen elements, which are generally disclosed in Wang.
Response to Arguments
Applicant’s arguments submitted with the Reply have been fully considered but are not persuasive. Applicant argues T-PLL is “characterized by malignant transformation of mature T-cells and specific genetic abnormalities,” whereas the leukemias disclosed in Wang are characterized by immature lymphocytes, B-cell malignancies, or pediatric population. (Remarks, p.9). Applicant asserts, “it is evident that . . . T-PLL . . . exhibits clear differences from ALL, AML, CLL, CML, CMML, and pediatric leukemia.” (Id.). Applicant further asserts the “core driver gene mutations/chromosomal abnormalities as well as dysregulation of proliferation and differentiation” are different between the types of leukemia. (Id.). Applicant next refers to a study in which Compound C was used as an agent for 10 subjects. (Id., p.11). Applicant argues: “The above clinical results demonstrates convincingly the safety and efficacy of APG-115 (Compound C) in treating T-PLL, thereby achieving unexpected technical effects.” (Id.).
Applicant’s arguments are primarily based on facts alleged by Applicant. Those facts are not supported by citations to the current record, prior art literature, or an expert affidavit. Thus, much of the Reply is mere attorney argument, which is not evidence and cannot be accorded much weight when compared to the evidence of record. Gemtron Corp. v. Saint-Gobtain Corp., 572 F.3d 1371, 1380 (Fed. Cir. 2009); In re De Blauwe, 736 F.2d 699, 705, 705 (Fed. Cir. 1984) (“It is well settled that unexpected results must be established by factual evidence. Mere argument or conclusory statements in the specification does not suffice”). To be fair, Applicant’s arguments on pp.9–10 regarding the classification of various types of leukemia appear to be consistent with the relevant literature. That is, T-PLL is a different subtype of leukemia than those mentioned in Wang. Nevertheless, Wang teaches a method of treating leukemia with the same compound via the same mechanism (inhibition of MDM2 and MDM2-related proteins). So, the differences between the instant claims and the disclosures in Wang have been acknowledged but are considered insufficient with respect to establishing non-obviousness. Applicant’s arguments on p.11 regarding a current study is not according any weight. Applicant does not explain what result was unexpected or present any data showing Compound C was relatively effective compared to other MDM2 inhibitors disclosed in Wang. Moreover, the results of Applicant’s study were not provided in a signed declaration by a person having firsthand knowledge of the facts. Thus, even if Applicant described what was unexpected when Compound C was compared to other MDM2 inhibitors, that discussion would not be considered factual evidence of non-obviousness. The rejection is maintained.
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Double Patenting
(i) Claims 1, 16, 17, 50, and 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of copending Application No. 18/727,848 (reference application).
The listings of claims at issue are not identical. The instant application does not claim a method of treating acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), myelodysplastic syndrome (MDS), or multiple myeloma (MM); and the reference application does not claim a method of treating T-cell prolymphocytic leukemia (T-PLL).
Although the listings of claims at issue are not identical, they are not patentably distinct from each other because they each cover a method of treating forms of leukemia with a MDM2 inhibitor, specifically Compound C.
It would have been prima facie obvious to a person of ordinary skill in the art to administer the same compound, with reasonable expectation of success, to subjects suffering from different forms of leukemia because the reference application suggests different forms of leukemia are treatable with a MDM2 inhibitor. To that end, one of ordinary skill in the art would have been motivated to administer Compound C to a subject having T-PLL because the reference application provides treating multiple forms of leukemia with Compound C.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(ii) Claims 1, 16, 17, 50, and 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 86, and 87 of copending Application No. 17/794,472 (reference application).
The listings of claims at issue are not identical. The instant application does not claim a method of treating adult acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myelogenous leukemia (CMML), or childhood leukemia; and the reference application does not claim a method of treating T-cell prolymphocytic leukemia (T-PLL).
Although the listings of claims at issue are not identical, they are not patentably distinct from each other because they each cover a method of treating forms of leukemia with a MDM2 inhibitor, specifically Compound C.
It would have been prima facie obvious to a person of ordinary skill in the art to administer the same compound, with reasonable expectation of success, to subjects suffering from different forms of leukemia because the reference application suggests different forms of leukemia are treatable with a MDM2 inhibitor. To that end, one of ordinary skill in the art would have been motivated to administer Compound C to a subject having T-PLL because the reference application provides treating multiple forms of leukemia with Compound C.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(iii) Claims 1, 16, 17, 50, and 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14–20 of copending Application No. 19/063,313 (reference application).
The listings of claims at issue are not identical. The instant application does not claim a method of treating adult acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myelogenous leukemia (CMML), or childhood leukemia; and the reference application does not claim a method of treating T-cell prolymphocytic leukemia (T-PLL).
Although the listings of claims at issue are not identical, they are not patentably distinct from each other because they each cover a method of treating forms of leukemia with a MDM2 inhibitor, specifically Compound C.
It would have been prima facie obvious to a person of ordinary skill in the art to administer the same compound, with reasonable expectation of success, to subjects suffering from different forms of leukemia because the reference application suggests different forms of leukemia are treatable with a MDM2 inhibitor. To that end, one of ordinary skill in the art would have been motivated to administer Compound C to a subject having T-PLL because the reference application provides treating multiple forms of leukemia with Compound C.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(iv) Claims 1, 16, 17, 50, and 51 are on the ground of nonstatutory double patenting as being unpatentable over claims 1–12 of U.S. Patent No. 12,287,338 (reference patent).
The listings of claims at issue are not identical. The instant application does not claim the measuring and comparing steps recited in the reference patent.
Although the claims at issue are not identical, they are not patentably distinct from each other because they each cover a method of treating T-cell prolymphocytic leukemia (T- PLL) by administering the same compound.
It would have been prima facie obvious to a person of ordinary skill in the art to modify the instant claims to include the measuring and comparing steps recited in the reference patent because the recited biomarkers were known in the art as being associated with cancers and the measuring and comparing steps are within the ability of one of ordinary skill in the art. To that end, one of ordinary skill in the art would have been motivated to add the preliminary steps before administering the compound shared by the claims to a subject having T-PLL.
Response to Arguments
Applicant’s arguments submitted with the Reply have been fully considered but are not persuasive. Applicant argues the rejections (i)–(iii) should be withdrawn for the same reasons “discussed above” for the prior art obviousness rejection. (Remarks, p.12). Accordingly, the rejections are maintained for the same reasons outlined in the prior art obviousness rejection. Regarding rejection (iv), Applicant overlooks the fact that the reference patent claims a method of treating T-PLL. Accordingly, the rejection is maintained.
Conclusion
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 C.F.R. § 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 C.F.R. § 1.17(a)) pursuant to 37 C.F.R. § 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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to submit an Automated Interview Request: http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/J.M.N./Patent Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
Prosecution Insights