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, 4, 15-16, 18-19, and 21 are pending.
Claims 2-3, 5-14, 17, 20 are cancelled.
Claims 1, 4, and 15-16 are currently amended.
Applicant’s election species of (1) step (iii) of claim 6 and (2) reducing the size of positivity charged patches from claim 5 in the reply filed on 04/14/2025 is re-acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Based upon current dependency, the Examiner believes that claims 1, 4, 15-16, 18, and 21 are not precluded by the species election and rejoins the claims in light of this understanding, noting that the species election requirement iterated in the 11/19/2024 Office Action is maintained.
Claims 1, 4, 15-16, 18-19, and 21 are under examination on the merits.
Priority
This application is a CON of PCT/EP2019/078970 and claims priority to European Patent Application No. 18202631.0, filed October 25, 2018.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim interpretation
Note that the recitation of a relative retention time is intended to mean the difference between the mutated antibody’s retention time as compared with that of one or more recited reference antibodies.
Note that recitations of ‘the antibody’ (see for example line 1 of part b of claim 1) are interpreted to refer back to the anti-HER3 reference antibody used in the claimed methods.
Note that where the claims recited an ‘improved half-life,’ this term has not been defined, but is being interpreted to mean an optimized half-life (longer than that of the reference antibody, but not so long as to cause undesirable effects, the broadest embodiment disclosed would be evidenced by the disclosure is an improved half-life as measured by an increase in the retention time (relative to the reference antibody) of 1-5 minutes.
Note that the recitation of ‘the antibody’ in line 1 of step b of claim 16 is deemed to refer to the reference anti-HER3 antibody used for the baseline/reference retention time.
Note that claim 19 is being interpreted as depending from claim 16 (because prior claim 7 depended from claim 16 prior to its cancellation in the 11/18/2025 claim amendments).
Note that “about” is defined in the instant specification as a range of +/- 20% of the thereafter following numerical value (see for example, lines 33-34 of page 14 of the specification).
Withdrawn Objections and Rejections
The objections to the drawings are withdrawn in light of the corrected figures received 11/18/2025. The rejections of claims 7 and 20 under 35 USC §112(a) are withdrawn as moot in light of the 11/18/2025 amendments cancelling claims 7 and 20. The rejections of the claims under 35 USC §103 and for double patenting are withdrawn as overcome by the altered claim scope resulting from the 11/18/2025 claim amendments.
New-Claim Objections
Claim 15 is objected to because of the following informalities: the recitation in lines 3-4 of “less than 1 minute mutations” should be amended to recite “less than 3 minutes, mutations” to accommodate and correspond with the claim scope of the claim amendments dated 11/18/2025 narrowing the scope of improvement to a 3-4 minute range. Additionally, the recitation in line 5 of “more than 5 minutes mutations” should be amended to recite “more than 4 minutes, mutations” to accommodate and correspond with the claim scope of the claim amendments dated 11/18/2025 narrowing the scope of improvement to a 3-4 minute range.
Claim 21 is objected to because of the following informalities: the recitation in line 2 of “less than about 1 minute and more than about 5 minutes” should be amended to recite “less than about 3 minute and more than about 4 minutes” to accommodate and correspond with the claim scope of the claim amendments dated 11/18/2025 narrowing the scope of improvement to a 3-4 minute range. Additionally, the recitation in line 3 of “less than 1 minute mutations” should be amended to recite “less than 3 minutes, mutations” to accommodate and correspond with the claim scope of the claim amendments dated 11/18/2025 narrowing the scope of improvement to a 3-4 minute range. Additionally, the recitation in line 5 of “more than 5 minutes mutations” should be amended to recite “more than 4 minutes, mutations” to accommodate and correspond with the claim scope of the claim amendments dated 11/18/2025 narrowing the scope of improvement to a 3-4 minute range.
Appropriate correction is required.
New-Claim Rejections - 35 USC § 112
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.
Claim 19 is 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.
Claim 19 depends from claim 7, which has been cancelled. Therefore, the metes and bounds of instant claim 19 are indefinite as drafted.
Conclusion
Claims 1, 4, 16, and 18 are allowed.
Claims 15, 19, and 21 are not allowed, but are subject to the objections and/or rejections set forth in this Office Action.
Allowable Subject Matter
Claims 1, 4, 15-16, 18-19, and 21 have been searched and are deemed to be free from the prior art (as noted in the previous office action dated 06/24/2025). The closest prior art is WO2015140126A1 (hereinafter referred to as Hoffman; as cited on the 11/26/2021 IDS). Hoffman teaches a method for influencing the in vivo half-life comprising the steps of a) determining the retention time of the antibody on an FcRn affinity chromatography column and b) determining the retention time of the antibody on an FcRn affinity chromatography column, whereby the presence of antibody-Fab-FcRn interaction in an antibody- Fc-FcRn complex influencing the in vivo half-life is determined if the retention time determined in step a) and the retention time determined in step b) are substantially different (see for example, the abstract at pg. 1). Note that Hoffman does not explicitly teach use of a first reference anti-HER3 antibody to provide a modified anti-HER3 antibody with an improved half-life, but that where the process steps are the same, the reference antibody used would not appear to materially affect the process, which is taught in such a way that one of ordinary skill in the art would expect the process to be applicable across many different antibodies, with a reasonable expectation of success (note for example Hoffman does not limit the process to any particular antibody or genus of antibodies). Hoffman further teaches that the half-life of a variant antibody may be determined to be improved relative to the parent antibody if the relative retention time of the variant/modified antibody is longer than that of the parent antibody (see for example pg. 5 bridging pg. 6; see also pg. 17 at the second paragraph). Hoffman goes on to teach measurement of retention times on an FcRn affinity chromatography column (see for example pg. 5 bridging pg. 6). Hoffman additionally teaches analysis of 12 antibody elution profiles using an FcRn affinity column with positive linear pH gradient elution (see Figure 2 and pages 41-42 and 45-46) wherein the wild-type antibody retention time was measured and compared to the mutant antibody retention time 2.2 minutes longer than the wild type (thereby exhibiting an improved half-life ad recited by instant claim 16, step d) (see pg. 67 and table 9 of Hoffman). Hoffman teaches embodiments where the modified antibody is retained 2.2 minutes longer than wild-type (aka the relative retention time is 2.2 minutes falling within the claimed range of more than 1 minute, but less than 5 minutes longer relative retention of modified antibody relative to reference antibody). Hoffman teaches that for coupling to streptavidin sepharose, one gram streptavidin sepharose was added to the biotinylated and dialyzed FcRn and incubated at 4°C overnight. The FcRn derivatized sepharose was filled in a 1 ml XK column and the FcRn column then was equilibrated with 20 mM 2-(N-morpholine)-ethanesulfonic acid (MES) sodium salt buffer containing 140 mM sodium chloride, pH 5.5 (buffer A), which is then used with an elution buffer (buffer B) comprising 20 mM Tris/HCl, with 140 mM NaCl, adjusted to pH 8.8, wherein 30 µg mAb/injection was used with a flow rate of 0.5ml/min (see page 97). Antibodies were eluted by a linear pH gradient from pH 5.5 to 8.8 within 120 minutes using 20 mM 2-(N-morpholine)-ethanesulfonic acid (MES) sodium salt, 140 mM sodium chloride, pH 5.5 and 20 mM tris(hydroxymethyl)aminomethane TRIS, 140 mM sodium chloride, pH 8.8 as eluents and a flow rate of 0.5 ml/min. The elution profile was obtained by continuous measurement of the absorbance at 280 nm.
Hoffman does not teach the specific, recited relative retention time of 3-4 minutes and the prior art fails to articulate any teachings guiding towards this relative retention time frame as being predictably linked to half-life.
Therefore, claims 1, 4, 15-16, 18-19, and 21, all drafted to require this relative retention time are deemed to be free from the prior art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Cymer et al (Evaluation of an FcRn Affinity Chromatographic Method for Igg1-Type Antibodies and Evaluation of Igg Variants. Bioanalysis, 9(17), 1305–1317) is deemed relevant to the teachings regarding the 80% and 20% equilibration and elution buffers for FcRn affinity chromatography.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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