DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1-4, 8-10, 12, 21 and 32-47 are pending upon entry of amendment filed on 2/5/26.
Claims 36-38 and 43 stand withdrawn from further consideration by the examiner, 37 CFR 1.142 (b) as being drawn to a nonelected invention.
Claim 1-4, 8-10, 12, 21, 32-35, 39-42 and 44-47 readable upon CD3 and DLL3 are under consideration in the instant application.
3. IN light of Applicant’s amendment to the claims and the response filed on 2/5/26, the rejection of record has been withdrawn.
4. The following new rejections are necessitated upon further consideration.
5. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
6. Claims 1-4, 8-10, 12, 21, 32-35, 39-42 and 44-47 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of reducing aggregates of bispecific antibody comprising holding a thawed antibody at temperature at room temperature upto 24 hours in the presence of benzyl alcohol, does not reasonably provide enablement for more.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use of the invention commensurate in scope with these claims.
The specification does not enable one of skill in the art to practice the invention as claimed without undue experimentation. Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed.Cir.1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of the skilled in the art to practice the claimed invention.
There is insufficient guidance in the specification as filed as to how the skilled artisan would use bispecific antibody at 45oC for at least 4 hours (no upper limit) without benzyl alcohol that is encompassed by the claimed invention. The currently amended claims are readable upon holding at 45oC for unlimited time.
Examples 1-6 exhibit hold time upto 24 hours at room temperature in the presence of the benzyl alcohol to reduce aggregates of thawed bispecific antibody. No examples showed extended time of encompassed by the claimed invention. Indeed, Fig 5 of the instant application showed the percent change of the high molecular weight above 1% and one sample of EGFRvIIIxCD3 showed closer to 10% in the absence of benzyl alcohol.
As such, given that the reduction of aggregates by holding upto 24 hours in the presence of benzyl alcohol is necessary, the storage time of 24 hours at room temperature cannot be extrapolated to unlimited time of storage at 45oC in the absence of benzyl alcohol as required by the currently amended claims.
To summarize, reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view or the quantity of experimentation necessary, the limited working example, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breath of the claims, it would take undue trials and errors to practice the claimed invention.
7. 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.
8. 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.
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.
9. Claims 1-4, 8-10, 12, 21, 32-35, 39-42 and 44-47 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S.Pub. 2017/055729 (newly cited) in view of U.S. Pub 2016/0075777 (newly cited) and WO2017/134140 (IDS reference, of record).
The ‘729 publication teaches reduction of aggregates antibody formulation of storage at room temperature and the formulation undergoes multiple freezing/thawing and freezing at -20oC ([0052-0054]).
The disclosure of the ‘729 publication differs from the instant claimed invention in that it does not teach the storage time of 4-8 hours and the use of bispecific antibody as in claim 1 further readable upon species of CD3 and DLL3 of the instant application.
The ‘777 publication teaches storage of drug substance at room temperature upto 24 hours exhibits change of high molecular weight aggregates less than 1% ([419-425]) and time profile of incubation (p. 29-31).
The ‘140 publication teaches the use and construct of CD3 and DLL3 bispecific antibody (claims 1-13, examples) and the bispecific antibody (BiTE) improvise half-life (SEQ ID NO:189-235) and thermostability with aggregation (p. 47-50). The figures disclose hinge-CH2-CH3 and a linker.
Given that the freezing and thawing at the claimed temperature ranges using the identical bispecific antibody, reduction of aggregates is expected property. In addition, bispecific antibody comprising CD3 and DLL3 are used, claims 46-47 are included in this rejection.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize bispecific antibodies taught by the ‘140 publication into the freezing and thawing methods taught by the ‘729 and ‘777 publications.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the utilization of bispecific antibody taught by the ‘140 publication improves half life as well as thermostability and reduction of aggregates.
From the teachings of references, it would have been obvious to one of ordinary skill in art to combine the teachings of the references and there would have been a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of the ordinary in the art at the time of invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
10. No claims are allowable.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YUNSOO KIM whose telephone number is (571)272-3176. The examiner can normally be reached Mon-Fri 8:30-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Yunsoo Kim
Patent Examiner
Technology Center 1600
March 10, 2026
/YUNSOO KIM/Primary Examiner, Art Unit 1641
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