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 .
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 1-18 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 domains or antibody fragments Applicant intends to cover by “antibody or fragment thereof”.
Claim 16 refers to the targeting ligand of claim 3. However, the targeting ligand is not defined by claim 16 and it is unclear what structural elements of the targeting ligand of claim 3 Applicant intends to cover.
Claims 17 and 18 refer to the targeting agent of claim 3. However, the targeting agent is not defined by claims 17 or 18 and it is unclear what structural elements of the targeting agent of claim 3 Applicant intends to cover.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 16 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maggi et al., Org. Biomol. Chem. 2016; 14 (31): 7544–7551 (Maggi).
Maggi teaches an approach in which tetrazines are used as tags for antibody modification:
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The above anticipates the claimed methods for preparing a tetrazine-modified antibody, within the meaning of section 102.
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 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., ACS Chem. Biol. 2021, 16, 4, 724–730 (Wang) in view of:
Luu, 1,2,4,5-TETRAZINE-BASED CLICK REACTIONS IN BIOORTHOGONAL CHEMISTRY, 2013, downloaded 25 Sept. 2026 from https://chemistry.illinois.edu/system/files/inline-files/SP13LongLuuFinalAbstract.pdf
(Luu); and
Rahim et al., Bioconjug Chem. 2015 Feb 18;26(2):352-60 (Rahim).
Wang teaches bioorthogonal CAR-NK therapy with targeting ligands and targeting agents that are bioorthogonal pairs. In particular, azide groups were introduced onto the surface of NK-92 cells. Bioorthogonal strain promoted the azide–alkyne cycloaddition click reaction of engineered NK-92 cells with alkyne modified cetuximab functionalized NK cells with the antibody. The resulting NK-92 cells were significantly more effective than the parent NK-92 cells in protecting against tumor development in a KRAS mutant mouse tumor model resistant to cetuximab treatment:
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Wang might not teach that the targeting ligand is tetrazine and the targeting agent is trans-cyclooctene. However, the tetrazine-trans-cyclooctene (Tz-TCO) ligation is the fastest known bioorthogonal click reaction, driven by an inverse-electron-demand Diels-Alder (IEDDA) cycloaddition. It is for that proposition that the examiner joins Luu (“Kinetic study in organic solvents by Sauer et al. reveals that tetrazines react with strained alkenes with a second-order rate constant of up to 104 M-1 s-1,2,3 which is several order of magnitude higher than that of existing bioorthogonal reactions. . . norbornene-, trans-cyclooctene-, and cyclooctyne bearing amino acids can be genetically encoded into desired proteins.
See also, Rahim:
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In this way, those of ordinary skill could have applied tetrazine and trans-cyclooctene in the manner required and in a predictable fashion for the purposes of providing a targeting ligand and a targeting agent. As outlined above, Wang teaches bioorthogonal CAR-NK therapy with targeting ligands and targeting agents that are bioorthogonal pairs. The secondary references are added for the proposition that tetrazine and trans-cyclooctene are applicable to this process. Specifically, the secondary references teach that the particular known technique of using tetrazine and trans-cyclooctene as bioorthogonal pairs was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to those methods that use bioorthogonal chemistry, such as that disclosed by Wang would have yielded predictable results. Accordingly, using a tetrazine targeting ligand and a trans-cyclooctene targeting agent would have been prima facie obvious.
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
