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 Amendment
The rejection of claims 21-44 under 35 USC § 102(a)(1) anticipated by Kozlowski et al. is withdrawn by the examiner in view of the amendment filed on 5/29/2026.
Since a new non-Final Office Action is follows, Applicant’s arguments will not be addressed.
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.
Claims 21-44 are rejected under 35 U.S.C. 103 as being unpatentable over Kozlowski et al. (US 7,659,361 B2) in view of Tumey et al. "Mild Method for Succinimide Hydrolysis on ADCs: Impact on ADC Potency, Stability, Exposure, and Efficacy" American Chemical Society 2014, pages 1871-1880.
Claim 21
Kozlowski teaches maleimide-thiol conjugates that form thiosuccinimide intermediates (col. 3, ll. 15-45; col. 10, ll. 5-40), ring opening of such intermediates to ring-opened succinamic acid products (col. 4, ll. 10-45; col. 5, ll. 1-25), and chromatographic separation of conjugates and isomeric products (col. 16, l. 52-col. 17, l. 23).
Kozlowski does not expressly disclose the specific mixture of ring-opened thiosuccinimide constitutional isomers recited in claim 21.
Tumey teaches hydrolysis of maleimide-thiol conjugates to produce ring-opened succinimide hydrolysis products and characterization of such products (p. 1872, Fig. 1; p. 1873, "Preparation and Characterization of Hydrolyzed Succinimide Linked ADCs"; pp. 1874-1875).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Kozlowski process by employing the ring-opening/hydrolysis products taught by Tumey because Tumey teaches that hydrolysis of thiosuccinimide linkages produces stable ring-opened products. One of ordinary skill in the art would have utilized the chromatographic separation methods expressly taught by Kozlowski to isolate and characterize the resulting ring-opened species.
Claim 22
Kozlowski teaches collection and recovery of chromatographic fractions (col. 16, l. 29-col. 17, l. 23), while Tumey teaches isolation of hydrolyzed succinimide products (pp. 1873-1875). Therefore, recovering a first eluate comprising one or more target compounds would have been obvious.
Claims 23-24
Further chromatographic purification of recovered fractions represents a routine purification technique well known in the art. Kozlowski teaches chromatography as a purification method for conjugate products and isomeric species (col. 16, l. 52-col. 17, l. 23).
Claims 25-33
Reverse-phase chromatography, alkyl-bonded stationary phases, aqueous/organic mobile phases, and acidic modifiers were conventional RP-HPLC conditions for purification of peptide and conjugate products at the time of the invention. Selection of such chromatographic conditions would have been an obvious matter of routine optimization.
Claims 34-39
Kozlowski teaches PEG polymers, polymer linkers, biologically active agents, and conjugated succinamic acid products (col. 2, ll. 40-65; col. 7, ll. 1-35; col. 9, ll. 5-30). Tumey further teaches application of the same maleimide-thiol chemistry in antibody-drug conjugates (pp. 1871-1873). Therefore, the additional polymer and conjugate limitations would have been obvious.
Claim 40
Both Kozlowski and Tumey expressly teach formation of ring-opened products by ring opening of a thiosuccinimide intermediate. Kozlowski (col. 4, ll. 10-45; col. 5, ll. 1-25); Tumey (p. 1872, Fig. 1).
Claims 41-43
Tumey teaches that hydrolysis of maleimide-thiol conjugates generates multiple ring-opened hydrolysis products (pp. 1872-1875), while Kozlowski teaches chromatographic separation of isomeric conjugates (col. 16, l. 52-col. 17, l. 23). Therefore, isolation of the recited ring-opened isomeric products would have been obvious.
Claim 44
Kozlowski and Tumey expressly teach ring opening of a thiosuccinimide group to form ring-opened products as discussed above with respect to claim 40.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAM M NGUYEN whose telephone number is (571)272-1452. The examiner can normally be reached Mon - Frid.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Prem C Singh can be reached at 571-273-6381. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TAM M NGUYEN/Primary Examiner, Art Unit 1771
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