DETAILED ACTION
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 .
Status of the Claims
Claims 1, 3, 5, 10, 13, 17, 19, 28-30, 32, 34, 49, and 51 are currently pending and are the subject of this Office Action.
Information Disclosure Statement
The references cited on the information disclosure statement(s) were considered and have been made of record.
Withdrawn Claim Rejections
All previous claim rejections under 35 U.S.C. 103 and NSDP are withdrawn in view of Applicant’s arguments and/or claim amendments.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1, 3, 5, 10, 13, 17, 19, 28-30, 32, 34, 49, and 51 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Nature of the invention/Breadth of the claims.
The present claims as written are so broad as to encompass any possible antibody/ fragment, evolved with any possible CDR mutation(s), so long as the substituted amino acid has a lower pI and results in a lower pI of the mutant antibody, exhibiting any possible activity; e.g., binding activity and prolonged half-life.
State of the prior art/Predictability of the art.
The prior art teaches conditionally active polypeptides for tumor targeting without pI modification (see, e.g., Short '839; art of record) and separately teaches pI modification for pharmacokinetic improvement (see, e.g., Igawa 2010; art of record).
Working examples.
The present application discloses results demonstrating pH dependent binding of three antibodies with pI modifications (see Affidavit filed 08/28/2024).
Guidance in the specification.
The specification identifies the reference, WO2017/078839, as a dictionary of terms, which defines "activity" as such: “The term "activity" as used herein refers to any function that a protein can perform, including catalyzing reactions and binding to a partner. For enzymes, the activity may be an enzymatic activity. For antibodies, the activity may be a binding activity (i.e., binding activity) between an antibody and its antigen(s)” (see WO2017/078839 at para. [37]).
Amount of experimentation necessary.
Undue additional research is required in order to determine which pI-modifying variable region mutations and in which particular antibodies would yield pH dependent activity, wherein activity encompasses any and all activity an antibody can perform. Additional research would be undue because there is no reasonable expectation that the proposed invention will be operable in all known antibodies and in resulting in pH-dependence for any and all antibody activities, e.g., prolonged half-life. Thus, there is insufficient information provided in order for an artisan to design and execute an experiment to test which mutations, for which antibodies, and for which activities will be pH-dependent.
For the reasons discussed above, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with this claim and it would require undue experimentation for one skilled in the art to use the claimed methods.
Response to Arguments
Applicant's arguments, filed 18 March 2026, with respect to the rejection(s) of the claims under 35 U.S.C. 103 and NSDP have been fully considered and are persuasive. Therefore, all previous rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made, as set forth above.
As stated previously, the present claims as written are so broad as to encompass any possible antibody/fragment, evolved with any possible CDR mutation(s), so long as the substituted amino acid has a lower pI and results in a lower pI of the mutant antibody, exhibiting any possible activity; e.g., lowering the pI of an antibody to increase binding to FcRn at acidic pH, which has been demonstrated in the prior art (see, e.g., Igawa 2010). Narrowing the claim scope to, e.g., a method of producing and selecting the particular conditionally active antibodies with altered binding activity, such as those reduced to practice in the present application, would overcome the claim rejections under 35 U.S.C. 112(a) and better position the instant application towards allowance.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEA S O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Thursday 9:00AM - 6:00PM PT.
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, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
Prosecution Insights