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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/20/25 has been entered.
1. Formal Matters
Claims 1 and 21-25 are pending and are the subject of this Office Action.
2. Claim Rejections - 35 USC § 112(a) – written description
Claim 1 remains rejected and new claims 21-24 are also rejected under 35 USC 112(a). First, it is noted that claim 1 recites “comprises 1, 2, 3, 4, or 5”; therefore, there is no upper limit to the number of substitutions which could, in theory, include conservative substitutions at every amino acid position in all 6 CDRs. It is also noted that “significantly” is subjective, though this is not being raised as part of the official rejection.
Applicants argue that conservative substitutions are taught in paragraphs [0292] – [0297] of the specification. Paragraph [0292] does provide numerous SEQ ID NOs for each CDR (e.g. 1-14, 15-28, 20-42); however, the Sequence Listing shows these sets are all duplicates of each other (i.e. SEQ ID NO:1-14 all show the same sequence). Clarification, or sequence alignments are requested, as this will help in the determination of adequate written description of the genus.
Currently, however, conservative substitutions still lead to unpredictability in the structure/function relationship of the antibody.
Coleman (page 3 of the Office Action dated 3/19/25) teaches that even a very conservative substitution may abolish binding or may have very little effect on the binding affinity (see pg. 35, top of left column and pg. 33, right column).
In addition, Lee (page 6, right column) teaches -
The functional consequences of sequence changes at the protein-protein interfaces (or even outside the interface viz., long-range interaction) are well known (Clark et al., 2006; Marvin and Lowman, 2003; Robinson et al., 2015). In the context of the test antibody designs, even a conservative substitution within a CDR loop (VH-Ser52Thr) can lead to drastic changes in the interatomic interactions with the adjacent residues, with potential to impact epitope-paratope contacts (Fig. 4C). The network approach employed in our antibody-engineering platform is able to capture the impact of amino acid substitutions in the FR and CDRs on antigen binding in the context of its structural environment that goes beyond the traditional view that conservative substitutions are less likely to impact function than non-conservative substitutions.
Furthermore, Wahlsten (Abstract) states that “Conservative substitutions of residues Asn68 and Asp71 greatly diminished mAb binding, identifying them as critical contact residues for anti-MIR mAbs.
Therefore, give these teachings, the Examiner still holds that adequate written description does not exist for the genus of conservative substitutions.
3. Nonstatutory Double Patenting
Claims 1 remains rejected and new claims 21-25 are also rejected for the reasons already of record on pages 6-7 of the Office Action dated 11/8/24 over U.S. Patent Nos 10,982,000 and 11,834,508. Applicants ask that these rejections be held in abeyance.
4. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
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, Joanne Hama, can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
Prosecution Insights