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 .
Election/Restrictions
Applicant's election with traverse in the reply filed on 4/29/2026 is acknowledged:
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The traversal is on the ground(s) that search and examination of the alleged inventions together would not place a serious burden on the Office. This is not found persuasive because Applicant has not stated that the Groups of inventions are not patentably distinct.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-11 cover the elected invention and are treated on the merits, below. Claims 12-27 are withdrawn from consideration as exclusively covering a non-elected invention.
Specification
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
This application contains polynucleotide and/or polypeptide sequence information. Applicant is required to review the specification for compliance with the above.
Claim Rejections - 35 USC § 112
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 1-11 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
It is unclear what regions and sequences of the recited anti-ErbB2 antibody Applicant intends to cover by “active fragment or variant thereof”.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over:
Baek et al., Analysis of Monoclonal Antibodies and Antibody-Drug Conjugates Using New Hydrophobic Interaction Chromatography (HIC) Columns, 2015, Thermo Scientific, downloaded 8 May 2026 from https://documents.thermofisher.com/TFS-Assets/CMD/posters/PN-21218-HPLC-Monoclonal-Antibodies-HIC-PN21218-EN-Rev1.pdf (Baek) in view of:
US 10,590,165 (US 165), or its counterpart, WO 2016123412; and
Behrens, Mabs, 01 Jan 2014, 6(1):46-53 (Behrens); and
Bhat et al., The Next Step in Homogenous Bioconjugate Development: Optimizing Payload Placement and Conjugate Composition, 2014, downloaded 23 March 2022 from https://bioprocessintl.com/manufacturing/monoclonal-antibodies/next-step-homogenous-bioconjugate-development-optimizing-payload-placement-conjugate-composition/ (Bhat I); and
U.S. Patent No. 8,741,291 to Bhat et al. (Bhat II); and
Panowski et al., mAbs, 2014, 6:1, 34-45 (Panowski).
Claims 1-7, separation of ADC’s: Baek teaches the recited HIC columns and mobile phases for ADC separation. Specifically, Baek teaches hydrophobic interaction chromatography (HIC) is a technique for separation of proteins and has been widely used as an orthogonal method to size exclusion chromatography and ion exchange chromatography for the characterization of mAb variants.
Baek teaches family of HIC columns designed for the analysis of mAbs and related biologics. Three different ligand chemistries-polyamide, amide and butyl-were developed for the analysis of a wide range of mAb samples. Separation of mAb aggregates, mAb fragments, oxidized mAbs, and antibody-drug conjugates were successfully carried out with excellent efficiency and high recovery.
Baek teaches the recited HIC separation techniques:
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Claims 1, 8-11, structure of the antibody: US 165 teaches the following ADC’s:
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The patent teaches that trastuzumab is recognized as ubiquitous in the art.
US 165 fails to explicitly teach conjugation via light chains.
Bhat discloses site-specific labeling of native mAbs at lysine residues in the kappa light chain constant domain of human mAbs by employing pentafluorophenyl esters as the active ester species for the conjugation:
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As Applicant notes, Bhat discloses that a drug can be conjugated on one light chain. See also description bridging columns 36 and 37.
Bhatt teaches how to conjugate in this manner:
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Therefore, conjugation to the light chains was within the purview of those of ordinary skill, and therefore, prima facie obvious.
Moreover, the references at least provide motivation to conjugate via lysine on the antibody light chain. Specifically:
at time of the invention, there had been a recognized problem of conjugating payloads to antibodies;
there had been a finite number of identified, predictable potential solutions to the recognized conjugation problem;
one of ordinary skill in the art could have pursued the known potential solutions, including lysine conjugation on the antibody light chain, with a reasonable expectation of success.
In this case, there had been a recognized problem of conjugating payloads to antibodies; there are a finite number of identified, predictable potential solutions to the recognized conjugation problem; and one of ordinary skill in the art could have pursued the known potential solutions, including lysine conjugation on the antibody light chain, with a reasonable expectation of success, as demonstrated by Behrens, above.
In this connection, it would have been obvious to one of ordinary skill in the art at the time the invention was made to choose from this finite number of conjugation options with a reasonable expectation of success of producing a functional ADC.
With regard to any unpredictability associated with different conjugation, the notion that unpredictability confers patentability in cases of different conjugation should be disregarded since a rule of law equating unpredictability to patentability, applied in this case, would mean that any new ADC based on a different conjugation would be separately patentable, simply because the formation and properties of each ADC must be verified through testing.
Here, the references provide the reasonable expectation of success, as outlined above. Namely, the references demonstrate the reasonable expectation of success since the references sufficiently characterize the instant ADC’s with a conjugation at a single light chain. Again, the expectation of success need only be reasonable, as it is here, and not absolute, (“obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).”).
Moreover, as explained previously, the claims only require that all the cytotoxic agent groups are conjugated to the lysine residues of the same peptide segment of the light chain of the antibody.
Specifically, US 165 teaches the following lysine conjugated ADC’s:
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The references teach that the product of this conjugation results in a heterogenous product mixture, which includes the instant light-chain conjugate, see Behrens:
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See also Panowski:
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The claims do not require a percentage of the product mixture which are ADC’s wherein all the cytotoxic agent groups are conjugated to the lysine residues of the same peptide segment of the light chain, that would distinguish from the references. In this regard, the references teach that the claimed product is made. This meets the claim. Specifically, the claims only recite preparation of ADC’s conjugated at lysine residues of the light chain and Behrens teaches that this product is made; and moreover, there is nothing in the claims that distinguishes the claimed product mixture since the required ADC is prepared.
Notwithstanding the fact that Bhat may teach that precise conjugation is not possible, Applicant’s claimed embodiment is taught. i.e.:
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See also Panowski:
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Again, it does not matter that the methods of the prior art prepare heterogenous mixtures, since the claim does not recite an amount or yield of ADC’s wherein all of the cytotoxic agent groups are conjugated to the lysine residues of the same peptide segment of the light chain that would distinguish from the references.
In this way, those of ordinary skill could have applied the recited HIC technique to the recited ADC’s in the manner required and in a predictable fashion for the purposes of obtaining a more purified and homogenous ADC product. As outlined above, the Baek teaches that antibody-drug conjugates are separated by HIC successfully with excellent efficiency and high recovery. The secondary references are added for the proposition that the recited ADC’s are applicable to this process. Specifically, the secondary references teach that the recited ADC’s were within the purview of those of ordinary skilled in the art. Baek teaches that separation of various ADC samples were obtained using the recited HIC columns and mobile phases. In this manner, those of ordinary skill would have recognized that applying the known technique to the recited ADC’s would have yielded predictable results. Accordingly, using the recited HIC methods to separate the recited ADC’s would have been prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-7 of copending Application No. 18688265 in view of Baek, US 165, Behrens, Bhat I, Bhat II, and Panowski. Although the claims at issue are not identical, they are not patentably distinct from each other.
The conflicting claims recite HIC of ADC’s. The difference between the methods in the conflicting claims and those recited in the rejected claims is that the conflicting may not recite the instant HIC with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the elements of the instant methods with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
The secondary references establish that the steps of the HIC and the instant ADC’s were within the purview of those of ordinary skill, as discussed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-7 of U.S. Patent No. 11903948 in view of Baek, US 165, Behrens, Bhat I, Bhat II, and Panowski. Although the claims at issue are not identical, they are not patentably distinct from each other.
The conflicting claims recite HIC of ADC’s. The difference between the methods in the conflicting claims and those recited in the rejected claims is that the conflicting may not recite the instant HIC with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the elements of the instant methods with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
The secondary references establish that the steps of the HIC and the instant ADC’s were within the purview of those of ordinary skill, as discussed above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
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