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 .
Detailed Action
This office action is in response to applicant’s communication filed on 10/27/25.
Claims 1-2, 5-11, 17-18, 20-21 and 23-37 are pending in this application and are being examined in this Office Action.
Applicant's election with traverse of Group 1, claims 1-2, 5-6 and 30-31, in the reply filed on 10/27/25 is acknowledged. The traversal is on the ground(s) that the claims relate to a single inventive concept. The applicant has included arguments for why the references of Evans et al. and CN 107102079 are not obvious over applicant’s claim 1. However, applicant’s arguments are not found persuasive because the claims of the various groups do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical feature due to the new art found on applicant’s claims, as a result of the examiner’s further search based on applicant’s elected species. See examiner’s 102/103 rejection over Kwon et al., as evidenced by Rosman, shown below.
Thus claims 7-11, 17-18, 20-21, 23-29 and 32-37 are withdrawn from consideration being drawn to the non-elected invention.
Applicant’s election of the following compound is acknowledged herewith:
PNG
media_image1.png
102
200
media_image1.png
Greyscale
Applicant’s elected species has been found allowable.
As a result, claims 1-2, 5-6 and 30-31 are being examined in this Office Action.
Priority
The applicant claims benefit as follows:
PNG
media_image2.png
166
470
media_image2.png
Greyscale
Objections
Claims 5-6 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
Claim 31 is rejected under 35 U.S.C. 112, second paragraph, because of a lack of antecedent basis. Claim 31 is rejected because it is dependent on a cancelled claim, claim 3. Applicant is advised to correct the claim language.
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 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 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. 1 03(a) are summarized as follows:
Applicant Claims
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue, and resolving the level of ordinary skill in the pertinent art.
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.
Claims 1-2and 30-31 are rejected under AIA 35 U.S.C. 103(a) as obvious over Kwon et al. (J. Med. Chem., 1989, 32, 1491-1496), as evidenced by Rosman (Taylor Pure Appl. Chem., 1999, 71, 1593).
Kwon et al. teaches formation of bis(aziridinyl)phospharamidate, by the reaction of the cyclophosphamide analogue (4b) with aqueous base at pH 12 to give the bis(aziridinyl)phospharamidate as the exclusive product. Kwon et al. teaches that the bis(aziridinyl)phospharamidate, has a CAS Registry Number of 120144-75-4. (page 1494, Table III, second compound 4b, and table footer; page 1494, second column, first paragraph; page 1495, first column, last paragraph, experimental section; page 1496, second column, last paragraph, last compound.)
The structure of the bis(aziridinyl)phospharamidate, with a CAS Registry Number of 120144-75-4, is below:
PNG
media_image3.png
458
584
media_image3.png
Greyscale
Since Kwon et al. teaches that the cyclophosphamide analogue (4b) starting material is in a phosphate solution and Kwon et al. used sodium phosphate from Sigma Chemical Co., it is reasonable to expect that the sodium (Na+) cation counterion is formed with the anionic bis(aziridinyl)phospharamidate product. This would give the following neutral and chemically stable sodium bis(aziridinyl)phospharamidate product as shown below:
PNG
media_image4.png
110
156
media_image4.png
Greyscale
Even if it does not, it would be reasonable to expect that the formed bis(aziridinyl)phospharamidate would complex with a sodium counterion, since naked negative charges are unstable in solution and since Kwon et al. teaches that formation of the bis(aziridinyl)phospharamidate product occurs with the addition of aqueous base at pH 12.
Kwon et al. is deficient in that it does not teach at least half of the hydrogen sites in the bis(aziridinyl)phospharamidate compound are deuterated (containing 4 or more deuteration sites).
Rosman is used as an evidentiary reference to show that the natural abundance of deuterium is 0.0115%, along with hydrogen’s greater abundance at 99.9885% (second element in the Table, second row).
Therefore, it would be prima facie obvious to one of ordinary skill in the art at the time of the invention, to isolate at least one molecule of the deuterated bis(aziridinyl)phospharamidate product that contains 4 or more deuteration sites, since Rosman teaches that deuterium is naturally abundant in hydrogen.
Thus only a single molecule of the bis(aziridinyl)phospharamidate product needs to have deuterium at 4 of the possible 8 deuterated sites, to read on applicant’s claims. It would be reasonable to expect this, since there are 6.02 x 1023 molecules (Avogadro’s Number) in one mole of the bis(aziridinyl)phospharamidate product.
Thus, it would be reasonable to expect that since the number of molecules in even a small amount of bis(aziridinyl)phospharamidate product is incredibly high (Avogadro’s Number), that at least one molecule would naturally contain deuterium in half of the hydrogen sites, especially since Kwon et al. teaches the bis(aziridinyl)phospharamidate product was isolated exclusively.
met.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer Cho Sawyer whose telephone number is (571) 270 1690. The examiner can normally be reached on Monday-Friday 9 AM - 6 PM PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-274-1690.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Jennifer Cho Sawyer
Patent Examiner
Art Unit: 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691