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. The art unit and the examiner of your application in the PTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Yunsoo Kim, Art Unit 1641, Technology Center 1600.
3. Claims 1-15 are pending upon entry of amendment filed on 6/16/22.
Applicant’s election of group I, claims 1-12 without traverse in the reply filed on 11/21/26 has been acknowledged.
Accordingly, claims 13-15 are withdrawn from further consideration by the examiner, 37 CFR 1.142 (b) as being drawn to a nonelected invention.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 1-12 are under consideration in the instant application.
The claims under consideration comprise one independent claim.
The current application relates a method of production of bispecific antibody construct comprising a first binding domain of FcγRIII and the second binding domain of CD30 comprising the steps of (a) chromatographic capturing of antibody construct from a solution, (b) eluting the antibody from the construct from the capture matrix, (c) reducing the pH in the solution of antibody construct to low pH of 2.5-3.9 for at least 40 hour; (d) neutralizing pH to the range of pH 4.5-8.0.
4. Applicant’s claims for foreign priority under 35 U.S.C. 119 (a)-(d) is acknowledged.
However, Applicant fails to provide a certified copy of the EP19219925.5 application as required by 35 U.S.C.119(b).
5. Applicant’s IDS filed on 7/25/22 and 11/21/25 have been acknowledged.
6. The oath filed on 7/25/22 has been acknowledged.
7. Claim 1 is objected to as the recited “steps” in line 3 of the claims failed to recite a conjunction “and” between steps (c) and (d).
8. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
9. Claims 1-12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 1-2 relate a method of production of bispecific antibody construct comprising a first binding domain of FcγRIII and the second binding domain of CD30 comprising the steps of (a) chromatographic capturing of antibody construct from a solution, (b) eluting the antibody from the construct from the capture matrix, (c) reducing the pH in the solution of antibody construct to low pH of 2.5-3.9 for at least 40 hour; (d) neutralizing pH to the range of pH 4.5-8.0 and the first binding domain of FcγRIII (CD16 antibody) and the second binding domain of CD30 set forth in SEQ ID Nos:1-12. However, the currently recited steps are relevant to the purification using the chromatographic methods. Generally, the production of bispecific antibody construct requires cloning into nucleic acid, transcription into vector system, and translation from the expression systems. IN absence of such procedural steps, no production of antibody would be made. Appropriate correction is required.
Claims 3, 9 and 10 recite Markush groups. The standard Markush group recites “selected from the group consisting of A, B, C and D” in MPEP 2173.05(h). However, the claims recited either no conjunction in claim 3 or uses conjunction “or” in claims 9 and 10, respectively.
Further, claim 3 recites “an amino acid set forth in SEQ ID NO” and “the amino acid set forth in SEQ ID NO”, interchangeably in items (a)-(d), and claim 13 recites “an amino acid set forth in SEQ ID”, respectively. However, in sequence analysis, the articles “an” and “the” are being used differently. While “an” is readable upon any fragments of the claimed amino acid sequence, “the” requires the entire full length of the claimed amino acid sequence. In identification of the antibody in terms of CDR’s of light and heavy chains, the CDR’s require the complete and the entire amino acid sequences. Appropriate correction is required.
10. 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.
11. Claims 1-12 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 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.
12. No claims are allowable.
13. 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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Yunsoo Kim
Patent Examiner
Technology Center 1600
February 20, 2026
/YUNSOO KIM/Primary Examiner, Art Unit 1641