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 1-6 and 9-15 are pending upon entry of amendment filed on 8/14/26.
Accordingly, claims 13-15 are withdrawn from further consideration by the examiner, 37 CFR 1.142 (b) as being drawn to a nonelected invention.
Claims 1-6 and 9-12 are under consideration in the instant application.
3. IN light of Applicant’s amendment to the claims filed on 8/14/26, the objection and the rejection under 35 U.S.C. 112 (b) (note sections 7-9 of the office action mailed on 2/25/26) have been withdrawn.
4. The following rejection remains.
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 1-6 and 9-12 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a purification of bispecific antibody construct comprising the SEQ ID NO:1-12 comprising chromatographic purification, elution and reduction by incubation of the eluted antibody at about pH 3 for 24 hours at 5oC, neutralization to pH 4-8 and formulation into the final product 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 reduction of eluted antibody at pH 2.5-39 at least 40 hours including at least 48 hours as in claim 8 of the instant application.
Examples 1-3 as disclosed in tables 1-10 showed incubation of the eluted antibody at pH 3 for 48 hours at 2-8oC or room temperature. As seen in table 2, the samples in acid elutes at pH 3.7 showed some detrimental activity between T3 of 24 hours and T4 of 48 hours of incubation.
Note samples at 5oC at pH 3.7 between 24 and 48 hours in A1, A3, C, E, F and G showed less yield in p. 30 of the instant application and Applicants admits the low yield is caused by the fragmentation (line 20). In addition, the loss of protein due to precipitation at low pH is seen in Table 4.
Although art recognizes incubation at pH 3 for 24 hours in WO2016/196230 (note p. 34, IDS reference), WO2018/159615 (IDS reference) in protein L chromatography (Example 1) and U.S.Pat 9,212,225 (Examples), no references mentioned extension of incubation for at least 48 hours. Rather, Jin reference (MABS, vol. 11, no. 8, p. 1479-1491, 2019) teaches purification of antibody using protein A chromatography. Jin et al. teaches use of pH 3.3 facilitates aggregation of protein and generally detrimental even at 5oC (p. 1480). Generally, 10minutes to 24 hours at maximum of incubation at pH 3 may be used in viral inactivation (p. 1482-1486).
The specification fails to provide sufficient guidance to direct a person of skilled in the art to make and achieve the intended use of the claimed invention without undue experimentation even the instant specification exhibits some detrimental analysis of acid reduction condition. It is unpredictable to develop antibody purification method comprising the reduction of eluted antibody at pH 2.5-3.9 at any temperature encompassed by the claimed invention in lack of successful studies disclosed by the instant application.
To summarize, reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view of 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.
Applicant’s response filed on 8/14/26 has been fully considered but they were not persuasive.
Applicant has asserted that the currently amended claims obviate the rejection of record. Applicant has further asserted that Table 3 of the instant application discloses pH value between 3.4 to 4 at different temperatures showed monomer percent higher than 75% and the claims are fully enabled.
Unlike Applicant’s assertion, the asserted monomer content of 75-91% disclosed in Table 3 of the instant application relates incubation at 5oC. Note current amendment is at room temperature. Further, the current specification does not define the end results of purification whether it is in terms of monomer content or yield. In lack of such definition, the yield after 48 hours of incubation at room temperature resulted in 11% in Table 2. As such, in lack of definition after purification, the Tables 2 and 3 showed controversial results and the specification is not fully enabled. The rejection is maintained.
7. No claims are allowable.
8. 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.
9. 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.
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, Misook Yu can be reached at 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
September 29, 2026
/YUNSOO KIM/Primary Examiner, Art Unit 1641
