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 .
Priority
This application is a national stage application under 35 U.S.C. § 371 of
International Application No. PCT/US20/62658, filed 12/01/2020, which claims the priority benefit of PRO Application No. 62/942,378, filed 12/02/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/14/2025, and 12/30/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of claims
Claims 4, 18, 25-26, 48-49, 59, 60, and 77-90 are pending in this application. Claims 4, 18, 26, and 77 are amended. Claims 1-3, 5-9, 10-17, 19-24, 27-47, 50-58, and 61-76 are cancelled without prejudice or disclaimer. Claims 49 and 86-90 are currently withdrawn as being directed to non-elected species from the Office Action dated 01/15/2025. Claims 4, 18, 25-26, 48, 59, 60, and 77-85 are currently under examination.
Applicant’s arguments, filed 12/30/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. They constitute the complete set presently being applied to the instant application.
The obviousness rejection below is repeated from the 10/01/2025 Office Action and modified in order to address the most recent amendments.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 4, 10, 18, 25, 26, 49, 59, 60, and 77-85 are rejected under 35 U.S.C. 103 as being unpatentable over Schafer (WO 2014/025960 A1).
The instant claims are directed to a method of treating or managing newly diagnosed multiple myeloma cancer, comprising orally administering to a patient in need (i) a therapeutically effective amount of 1.0-1.6 mg Compound A or A-S in combination with (ii) a proteasome inhibitor (bortezomib, carfilzomib, marizomib (salinosporamide A), ixazomib) and 10-40 mg dexamethasone wherein compound A or A-S is administered in an amount of about 1.0-1.6 mg, once daily for a 21 or 28 day cycle for 1-9 cycles.
Schafer et al. teach the compound of formula I (3-(4-((4-(morpholino methyl)benzyl)oxy) -l-oxoisoindolin-2-yl)piperidine-2,6-dione in a method of treating cancer, including refractory cancer [0038]. Schafer also discloses the (S) version of the compound of formula I as formula I-S ((S)-3-(4-((4- (morpholinomethyl)benzyl)oxy)-l-oxoisoindolin-2-yl)piperidine-2,6-dione) may be used in place of formula I and is structurally equivalent to compound A-S of the instant claims [0039]. Schafer teaches embodiments in which the therapeutically or prophylactically effective amount is about 0.1, about 0.2, about 0.5, about 1, about 2 mg per day [00266]. Schafer also teaches that a compound of formula I is administered in an amount of 0.5-50 mg per day [00267]. Schafer discloses a method of treatment in an embodiment for multiple myeloma [0044].Schafer also teaches an embodiment wherein a second active agent is a proteasome inhibitor of bortezomib, salinosporamide A, and carfilzomib [0246]. Schafer also teaches an embodiment where the compound of formula I is administered for 21 days followed by seven days rest in a 28 day cycle [00183]. Schafer teaches oral administration of formula I [00289]. Schafer Discloses “[t]he combined use of the compound of Formula I, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, provided herein and transplantation therapy provides a unique and unexpected synergism.” [00334]. Schafer also discloses an embodiment in which a newly diagnosed multiple myeloma is treated with a compound of formula I [00343]. Schafer teaches an embodiment in which formula I is administered with dexamethasone to a subject with various stages of multiple myeloma. Schafer also discloses an embodiment in which the proteasome inhibitor is bortezomib [00246]. Schafer teaches that the second active agent is administered intravenously or subcutaneously once or twice daily ranging from 1-1,000 mg with the specific amount of the second active agent depending on the specific agent used, the type of disease being treated or managed, the severity and stage of disease, and the amount of the compound of Formula I provided herein and any optional additional active agents concurrently administered to the patient [00290]. Schafer also teaches an embodiment in which a combination treatment of formula I and a second active ingredient are administered to a patient for a period of 1-24 cycles [00350]. Schafer also discloses "The combined use of the compound provided herein and conventional therapy may provide a unique treatment regimen that is unexpectedly effective in certain patients. Without being limited by theory, it is believed that the compound of Formula I may provide additive or synergistic effects when given concurrently with conventional therapy" [00329].
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to administer a combination therapy of a compound of formula I and I-S with a proteasome inhibitor and dexamethasone to a patient with a newly diagnosed multiple myeloma in need thereof following the teachings of Schafer because Schafer discloses embodiments wherein a compound of formula I or I-S is administered in combination with dexamethasone and bortezomib in the dose ranges, cycles and duration of treatment as in the instant claims. See MPEP 2144.05. Furthermore, the applicants disclosed compounds of compound A and A-S are equivalent to the prior art disclosed by Schafer as shown below.
PNG
media_image1.png
310
561
media_image1.png
Greyscale
PNG
media_image2.png
277
528
media_image2.png
Greyscale
A person having ordinary skill in the art would have been motivated to administer a
combination therapy of a compound of formula I and I-S with dexamethasone and the
proteasome inhibitor of bortezomib in a dose regimen of 1.0-1.6 mg of formula I and I-S, 10-40
mg dexamethasone and an effective amount of bortezomib in 21-28 day cycles for 1-9 cycles
following Schafer because of the beneficial additive or synergistic effects of the disclosed
compounds on patients when administered concurrently with conventional cancer therapy and
would have naturally arrived at the instantly claimed methods. Therefore the invention as a
whole would have been prima facie obvious to one of ordinary skill in the art prior to the time
the instant application was filed based on the current record as evidenced by the reference.
Response to Arguments
Applicant's arguments filed 12/30/2025 have been fully considered but they are not persuasive.
Applicant argues Claim 4 is nonobvious over Schafer at least because D1 (Schafer WO2014/025960A1) does not explicitly state "wherein the compound is administered in an amount of about l.0 mg, about l.3 mg, or about l.6 mg" as recited in the instant claim (emphasis added).
Claim 4 is drawn to treating multiple myeloma by administering about l.0 mg, about l.3 mg, or about l.6 mg of compound A with a proteasome inhibitor. Schafer teaches that a compound of formula I is administered in an amount of 0.5-50 mg per day [00267] Schafer also discloses embodiments in which the therapeutically or prophylactically effective amount is about 0.1, 0.2, 0.5, 1, or about 2 mg per day [00266]. As disclosed by Schafer, the compound of formula I and compound A of the instant claims share the same chemical structure. The amount of about l.0 mg, about l.3 mg, or about l.6 mg compound A administered in claim 4 is rendered obvious by Schafer’s teaching of administering 0.5-50 mg of formula I per day and more specifically about 1 to 2 mg per day. See MPEP 2144.05
Applicant also argues synergistic and clinically significant efficacies exhibited by the compound specifically at about 1 mg, 1.3 mg, or 1.6 mg are surprising and could not have been predicted based on the reference cited by the Office.
Schafer discloses “The combined use of the compound of Formula I, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, provided herein and transplantation therapy provides a unique and unexpected synergism.” [00334] Furthermore, as disclosed above, a dose of 1 mg formula I is disclosed by Schafer. A skilled artisan following the teachings of Schafer would have found it obvious to try a 1 mg dose of formula I in a combination multiple myeloma therapy with a proteasome inhibitor for administration to a patient in need thereof following the disclosures of Schafer.
A person of ordinary skill would have been motivated to try a 1 mg dose of formula I for administration in a combination multiple myeloma therapy with a proteasome inhibitor as taught by Schafer because Schafer disclosed the combined use of formula I and a second conventional therapy wherein a second active agent is a proteasome inhibitor (bortezomib, salinosporamide A, and carfilzomib) to be unexpectedly effective in certain patients. Schafer also disclosed “Without being limited by theory, it is believed that the compound of Formula I may provide additive or synergistic effects when given concurrently with conventional therapy.” Therefore the synergistic and clinically significant efficacies exhibited by the compound of formula I in the specific amounts of about 1 mg, 1.3 mg, or 1.6 mg were suggested by the Schafer reference cited by the Office. Even if Applicants result were considered to be unexpected in view of the prior art, the instant claims are not commensurate in scope with the alleged unexpected results. See MPEP 716.02, particularly 716.02(d).
Conclusion
All claims are rejected, no claims are allowed.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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 use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
Prosecution Insights