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 of Group I (claims 1 and 4-21) in the reply filed on 7/21/2026 is 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)).
Claims 13-18 and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/21/2026.
Specification
The use of terms such as Halotag, PLURONIC, and MEGASTOKES which are a trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Examiner’s Comment
The Examiner has cited particular columns and line numbers, paragraphs, or figures in the references as applied to the claims for the convenience of the Applicant. Although the specified citations are representative of the teachings in the art and are applied to the specific limitations within the individual claim, other passages and figures may apply as well. It is respectfully requested from the Applicant, in preparing the responses, to fully consider the references in entirety as potentially teaching all or part of the claimed invention, as well as the context of the passage as taught by the prior art or disclosed by the Examiner.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 4, 6, 9, 11-12, and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kirkland et al. (US 2020/0386748 A1, published 12/10/2020, cited on the 5/21/2025 IDS) in view of Darzins et al. (US 2011/0171673 A1, published 7/14/2011, corresponding US Patent cited on the 5/21/2025 IDS).
Regarding claims 1, 4, 6, and 9, Kirkland teaches systems and compositions for the detection of analytes in a sample through quantification of a bioluminescent signal [Abstract]. The composition of Kirkland comprises a luminogenic substrate, a target analyte binding agent comprising a target analyte binding element and a polypeptide component of a bioluminescent complex, and a complementary component of a bioluminescent complex [claim 157]. Exemplary luminogenic substrates include coelenterazine and analogs or derivatives thereof [0053]. In some embodiments, the composition may comprise a capture protein comprising a modified dehalogenase, such as a HaloTag, capable of forming a covalent bond with a capture ligand comprising an alkyl halide with the formula A-X where A is (CH2)6 and X is Cl. [0292-0293]. The capture protein may be linked to a peptide component of the bioluminescent complex, and the capture ligand linked to a target analyte binding element [0292]. The target analyte binding agent may further comprise a fluorophore capable of being activated by energy transfer (i.e. energy acceptor) from the bioluminescent polypeptide [0289; claim 167]. Suitable fluorophores include xanthene derivatives such as rhodamine and analogs thereof [0290]. Kirkland further teaches that the composition may comprise of a polymer to reduce decomposition and increase stability of the composition [0370]. The polymer may comprise a block copolymer comprising at least one poly(propylene oxide) block and at least one poly(ethyleneoxide) block (i.e. poloxamer), such as poloxamer 188 (reads on instant claim 9) [0057].
Kirkland does not explicitly disclose a compound with the instantly claimed formula. Darzins teaches a compound of formula (I): R-linker-A-X, wherein R is one or more functional groups; the linker is a multiatom straight or branched chain including C, N, S, or O (reads on instant claim 6); and A-X is a substrate for a dehalogenase, wherein X is a halogen [0009] and A is (CH2)n where n is 2 to 10 [0208] (i.e. A-X is an alkyl halide). R comprises of functional groups with properties that facilitate detection [0172], such as luminescent proteins, fluorophores, and chromophores [0172]. Exemplary functional groups include rhodamine dyes (reads on instant claim 4) and coelenterazine [0175]. Darzins further teaches that the linker can provide physical separation between the reactive group recognized by the dehalogenase and the functional group, so that the reactive group is able to interact with the reactive residue in the dehalogenase to form a covalent bond [0008]. Thus, it would be obvious to one of ordinary skill in the art to modify the teachings of Kirkland with that of Darzins to modify the composition of Kirkland to comprise a compound of formula (I) wherein the linker facilitates covalent bonding between the dehalogenase and capture ligand comprising an alkyl halide, in order to form the analyte detection complex.
Regarding claims 11 and 12, Kirkland teaches that the composition may comprise a buffer such as a phosphate buffer, tricine, or 2-(N-morpholino)ethanesulfonicacid [0383].
Regarding claim 19, Kirkland teaches that the composition may be in the form of a lyophilized powder [0388].
Regarding claim 20, Kirkland teaches that the composition may be a solution [0389].
Regarding claim 21, Kirkland teaches that the composition may comprise of a polymer to reduce decomposition and increase stability of the composition [0370]. Kirkland does not explicitly state what type of decomposition is reduced. However, the instant limitation is a property of the claimed composition. Since Kirkland and Darzins make obvious the claimed composition, and a composition and its properties are inseparable, the claimed properties are presumed to be inherent. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP 2112.01.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Kirkland et al. (US 2020/0386748 A1, published 12/10/2020, cited on the 5/21/2025 IDS) and Darzins et al. (US 2011/0171673 A1, published 7/14/2011, corresponding US Patent cited on the 5/21/2025 IDS), as applied to claim 1 and 4 above, and further in view of Lavis et al. (US 2021/0085805 A1, published 3/25/2021).
Regarding claim 5, Kirkland and Darzins do not explicitly teach the claimed composition wherein the rhodamine dye is Janelia Fluor 552. Lavis teaches Janelia Fluor 552 conjugated to a haloalkane (JF552-HaloTag ligand) [0131; pg. 24, ref. 9HTL] (pictured below)
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This structure reads on a compound with the formula R-linker-A-X wherein R is a fluorophore; the linker is multiatom straight or branched chain; A is (CH2)4-20; and X is a halide (see also, Instant specification pg. 21, bottom left compound). Kirkland and Darzins teach rhodamine dyes as suitable fluorophores of the instant invention (discussed above in the 103 rejection of claim and 1, 4, 6, and 9). The selection of a known material based on its suitability for its intended use is prima facie obvious. MPEP 2144.07. Lavis teaches that Janelia Fluor 552 may be used as a probe/tag in methods for detecting a target [Abstract]. Thus, it would be obvious to select Janelia Fluor 552 as the rhodamine dye of the composition made obvious over Kirkland and Darzins. Furthermore, Lavis teaches that Janelia Fluor 552 has improved cell-permeability [0130], thus it would also be obvious to select this rhodamine dye due to its wider applicability and improved signaling [0132].
Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kirkland et al. (US 2020/0386748 A1, published 12/10/2020, cited on the 5/21/2025 IDS) and Darzins et al. (US 2011/0171673 A1, published 7/14/2011, corresponding US Patent cited on the 5/21/2025 IDS), as applied to claim 1 and 6 above, and further in view of Levin et al. (US 2020/0199140 A1, published 6/25/2020).
Regarding claims 7 and 8, Darzins teaches that the linker may be cleavable [0008], but neither Kirkland nor Darzins explicitly teaches a linker wherein the cleavable moiety is an allyl-heteroatom group or a propargyl-heteroatom group. Levin teaches cell-permeable, cell-compatible, and chemoselectively-cleavable linkers for tethering functional elements such as a cellular interaction element and a capture element [Abstract]. The linkers of Levin have applications in detection, isolation, and immobilization of cells, proteins, and molecules of interest [0003]. The structure comprising the linker may have the formula: Z-Y-L1-M-L2-A-X, wherein Z is a cellular interaction element; Y is a chemoselectively-cleavable moiety; L1 is a first linker moiety; M is an alkyl carbamate group; L2 is a second linker moiety; A is an alkyl group; and X is a halogen [0013]. L2-A may separate M and X by 6 to 18 linearly connected atoms [0013]. Levin further teaches that the chemoselectively-cleavable moiety may be selected from an allyl-heteroatom group or a propargyl-heteroatom group [00013]. The alkyl halide (A-X) may act as the capture element [0007] and the cellular interaction element (Z) may be a dehalogenase [0017] (see also para. 0023). The structure may further comprise a functional element tethered to the cellular interaction element or to the capture element [0134], such as a fluorophore [0139]. Levin teaches that the cleavable linker allows for the binding of the capture elements and cellular interaction elements to be reversible [0025]. This allows for the targets bound to a cellular capture agent (e.g. dehalogenase) to be released [0151], which allows the composition to be used in broader applications for capture, purification, characterization, and other analysis of cellular targets [see e.g., paras. 0151-0155]. It would be obvious to one of ordinary skill to select a linker comprising a cleavable moiety such as an allyl-heteroatom group or a propargyl-heteroatom group for use in the instantly claimed composition, in order to allow for reversible target binding and use in a wider range of applications.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Kirkland et al. (US 2020/0386748 A1, published 12/10/2020, cited on the 5/21/2025 IDS) and Darzins et al. (US 2011/0171673 A1, published 7/14/2011, corresponding US Patent cited on the 5/21/2025 IDS), as applied to claim 1 and 9 above, and further in view of Dart et al. (US 2020/0109146 A1, published 4/9/2020).
Regarding claim 10, Darzins and Kirkland do not explicitly teach the claimed composition wherein the poloxamer is poloxamer 407. Dart teaches compositions and methods for stabilizing luminogenic substrates such as coelenterazine [0006]. Luminogenic substrates can decompose during storage, thereby resulting in waste and reduced sensitivity and reproducibility of luminescent measurements derived from biological assays that employ the luminogenic substrate [0004]. Dart teaches that compositions comprising coelenterazine and a polymer stabilizes the coelenterazine against decomposition as compared to a composition that does not contain the polymer [0092]. Dart teaches that the polymer may be a poloxamer [0101]. Suitable poloxmers include poloxamer 188 and poloxamer 407 [0105]. Substitution of equivalents known for the same purpose is prima facie obvious. MPEP 2144.06. Thus, it would be obvious to one of ordinary skill to modify the teachings of Darvins and Kirkland with that of Dart, and substitute poloxamer 188 (as taught by Kirkland) with poloxamer 407.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA LYNN CHI whose telephone number is (571)272-0026. The examiner can normally be reached Monday - Friday 9 am-5pm ET.
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/AMANDA LYNN CHI/Examiner, Art Unit 1613
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
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