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 .
Claims 1-2, 5, 11-12, 16, 34, 46, 48-50, 53, 55-56, 60, 62, 65, 68, 70-71, 73-74, 76, 79, 85, 87, 107, and 115-120 are pending.
Applicant’s election without traverse of Group I, claims 1-2, 5, 11-12, 16, 34, and 115 in the reply filed on 10/03/2025 is acknowledged.
Claims 46, 48-50, 53, 55-56, 60, 62, 65, 68, 70-71, 73-74, 76, 79, 85, 87, 107, and 116-119 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group/invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/03/2025.
Claims 3-4, 6-10, 13-15, 17-33, 35-45, 47, 51-52, 54, 57-59, 61, 63-64, 66-67, 69, 72, 75, 77-78, 80-84, 86, 88-106, and 108-114 are cancelled.
Claim 120 is new.
Claims 1-2, 5, 11-12, 16, 34, 115, and 120 are under examination on the merits.
Priority
This application is a 371 of PCT/EP2021/051645, filed 01/25/2021, which claims benefit of priority to US Provisional Application No. 62/965,443, filed 01/24/2020, and further claims benefit of priority to EP 20154216.4, filed 01/28/2020.
Biological Deposit
The deposit in The Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures on January 16, 2019 with a deposit number DSM ACC3350, was made under conditions that are consistent with those specified in the rules of the Budapest Treaty, including the provision that requires, with one possible exception (37 CFR 1.808(b) ), that all restrictions on the accessibility be irrevocably removed by the applicant upon the granting of the patent. Ex parte Hildebrand, 15 USPQ2d 1662 (Bd. Pat. App. & Int. 1990).
Withdrawn Objections/Rejections
The objection to the specification is withdrawn in light of the corrective amendments dated 02/27/2026. The objection to claim 34 regarding the ELISA acronym is withdrawn in light of the corrective amendments dated 02/27/2026. The rejections of claims 1-2, 5, 8-9, 11, 12, 16, 34, and 115 under 35 U.S.C. 112(a) are withdrawn in light of the corrective amendments dated 02/27/2026. The rejections of claims 2, 5, 11, 12, and 34 under 35 USC §112(b) are withdrawn in light of the corrective amendments dated 02/27/2026. The rejection of claim 16 under 35 USC §112(b) for lack of antecedent basis is withdrawn upon further consideration of the inherency of the LCVR/HCVR. The rejections of the claims under 35 USC §102 and §103 are withdrawn in light of the 02/27/2026 claim amendments requiring the recited CDR1-6 for all of the claims.
Maintained-Claim Interpretation
The recitation of the respective sequences of the antibody produced by the single clone hybridoma cell line 7C10-C5 are presumed to be reflected in tables 2 and 3 (spanning pages 123-126 of the specification).
Where CDR amino acid sequences are recited, it is noted that the Kabat or Chothia system is used for the CDR numbering determinations, where the Kabat system is preferred (see for example, page 13 of the specification).
New-Claim Objections
Claim 34 is objected to because of its dependence from rejected base claim 115, but would be allowable if rewritten in independent form.
Maintained-35 USC § 112(b)
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.
Claims 16 and 115 remain 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 16, the recitation that the HCVR and/or LCVR “…has the amino acid sequence…” is indefinite. The skilled artisan is left to dispute whether the sequence comprising or consisting of the recited amino acid sequence is encompassed by the claim as presently drafted. Adoption of more clear and convention (such as ‘comprises’ language or ‘consists of’ language, but not’ comprises or consists of’ language are suggested to remedy the noted ambiguity).
Regarding claim 115, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 115 recites the broad recitation “…comprising…”, and the claim also recites “…or consisting of…” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Applicant’s Arguments and Responses
A. Applicant argues that amendments to the claims overcome the rejections of claims 16 and 115 under 35 USC §112(b).
Response: No amendment has been made to claim 16. The amendments dated 02/27/2026 to claim 115 fail to remedy or remove all instances of ‘comprises/comprising or consists/consisting of’ language (see for example, parts (i)-(iv) of claim 115). Therefore, the rejections have not been overcome by the 02/27/2026 claim amendments. The rejections are maintained at this time.
Conclusion
Claims 1-2, 5, 11-12 and 120 are allowed.
Claims 16 and 115 are rejected.
Claim 34 is objected to.
Notice:
The claim amendments dated 02/27/2026 result in each of the instant claims reciting and requiring the previously noted novel CDR1-6 set(s) because claim 1 recites, at part (a) the novel sets of HCDR3-1 comprising SEQ ID NOs: 2-4 and LCDR3-1 comprising SEQ ID NOs: 5-7, and alternatively recites, at part (b) the CDRs noted in tables 2 and 3 (spanning pages 123-126 of the specification; depicting the CDRs as determined by Chothia, AbM, Kabat, Contact, and IMGT methods), where the disclosed CDRs of Tables 2 and 3 have been searched and are deemed to be free from the prior art. All other claims depend from claim 1 and, thereby, incorporate the novel CDRs making all of the instant claims free from the prior art (noting further the surprising advantages of the antibody over prior art antibodies; see for example, pages 95, 99, and 147 of the instant specification).
The closest prior art is Tolstykh et al (Embo J 19, 2000, pages 5682-5691; as previously cited in the office action dated 12/01/2025), which teaches the 4D9 antibody which specifically binds to the methylated C-terminal sequence (and methylated leucine 309) of instantly recited SEQ ID NO: 18 (of PP2Ac), but does not teach an antibody which comprises the instantly claimed HCDR1-3 and LCDR1-3 sequences or the HCVR and LCVR sequences required by the instant claims.
Furthermore, while the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. For example, Al Qaraghuli et al (2020, Nature Scientific Reports 10:13969; as previously cited in the office action dated 12/01/2025), state that the six CDRs form a continuous surface to form the paratope that binds the epitope of the cognate antigen. This suggests that a change in the CDR sequence may result in a conformationally different paratope which may fail to bind target as claimed. Here, a mutation in the CDRs may result in a paratope unable to bind PP2A as claimed. Rabia et al (2018, Biochemical Engineering Journal 137:365-374; as previously cited in the office action dated 12/01/2025) teach what effects mutations can have on an antibody's stability, solubility, binding affinity and binding specificity. Rabia et al report that an increase in antibody affinity can be associated with a decrease in stability (p. 366, col. 2 last paragraph; Fig. 2). Tiller et al (2017, J. Biol. Chem. (2017) 292(40) 16638–16652; as previously cited in the office action dated 12/01/2025) and Tsuji et al (2022, J Virol 96:e00071-22; as previously cited in the office action dated 12/01/2025) teach that mutations in the CDRs (especially HCDR3 are unpredictable and accompanied by tradeoffs in performance (for example increased affinity may lead to decreased specificity); see references in their entirety paying particular attention to the abstract of Tiller et al and the abstract and results section of Tsuji et al). The above cited references underscore the unpredictability of even a single mutation in the CDRs.
Therefore, a difference of a single amino acid in the VH/HCDRs or VL/LCDRs domain is enough to render an antibody free of the art. In the instant Application, the recitation of novel CDR/HCVR/LCVR sequences is sufficient to render the antibody free of the art.
Regarding predictability of antibody-antigen binding and/or prediction/association of binding pairs, the prior art supports that antibody-antigen binding is highly complex and unpredictable. Machine-learning models and in silico approaches generally remain unable to predict antigen-antibody binding, even when sifting between data sets of known antibodies and antigens to predict compatible binding and often produces incorrect models/pairings (see for example, Lowe, D. (Predicting Antibody Binding: No Champagne Just Yet, Science (2026); obtained from: http://www.science.org/content/blog-post/predicting-antibody-binding-no-champagne-just-yet). Underscoring the unpredictable state of the art, Subedy et al (bioRxiv 2026.01.17.700115; doi: https://doi.org/10.64898/2026.01.17.700115 (2026)) teach that achieving accurate predictions of complete antibody–antigen complexes is still an open challenge. Likewise, Spoendlin et al (Nat Mach Intell 7, 1755–1767 (2025). https://doi.org/10.1038/s42256-025-01131-6) teach that the flexibility of antibody complementarity-determining region (CDR) loops influences binding affinity and specificity, making it a key factor in understanding and designing antigen interactions, but predicting protein flexibility remains challenging, as current structure prediction tools struggle to capture multiple conformational states, particularly for antigen receptor CDRs.
Accordingly, absent empirical determination, one skilled in the art would be unable to predict or envision the CDRs/HCVR/LCVR or sequences recited/required in the instant claims for binding to PP2Ac, as claimed.
As such, the instant claims 1-2, 5, 11-12, 16, 34, 115, and 120 are deemed to be free from the prior art. Claims 16 and 115 remain subject to the pending rejections under 35 USC §112(b) above. Claim 34 is subject to the pending claim objection above. Claims 1-2, 5, 11-12, and 120 are allowed as they are free from the art and from other reasons of refusal (other rejections/objections). Rejoinder will be considered once all of the elected claims are deemed to be in condition for allowance. See MPEP 821.04, which states that the propriety of a restriction requirement should be reconsidered when all the claims directed to the elected invention are in condition for allowance, and the nonelected invention(s) should be considered for rejoinder.
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.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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