DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicants’ amendment to the claims filed on 03/25/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 1-15, 29, and 42-45 pending.
Election/Restrictions
4. Applicant's election with traverse of Group I, claims 1-15, 29 and 43-45 in the reply filed on 03/25/2026 is acknowledged. The traversal is on the ground(s) that claims 1-15, 29 and 42-45 share a special technical feature that makes a contribution over Moustaqil and McConnel. This is not found persuasive in view of the prior art rejections set forth below.
The requirement is still deemed proper and is therefore made FINAL.
5. Claim 42 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/25/2026.
Claims 1-15, 29 and 43-45 are pending and examined on the merits.
Priority
6. Acknowledgement is made of applicants’ claimed domestic priority to U.S. Provisional Application No. 63/119160, filed on 11/30/2020.
Information Disclosure Statement
7. The IDSs filed on 07/14/2023 and 03/25/2026 have been considered by the examiner and copies of the Form PTO/SB/08 are attached to the office action.
Drawings
8. The Drawings filed on 05/19/2023 are acknowledged and accepted by the examiner.
Claim Rejections - 35 USC § 112(b)
9. 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.
10. Claims 5 and 44 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.
Claims 5 and 44 contain the trademark/trade name HaloTag. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the split reporter and, accordingly, the identification/description is indefinite.
11. Claim 8 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.
Regarding claim 8, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
12. 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.
13. Claim(s) 1-4, 6-9, 14-15, 29, 43, and 45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Moustaquil et al. (International Journal of Molecular Sciences, 2017; cited on IDS filed on 07/14/2023) in view of McConnel et al. (AU 2007200365 A1; cited on IDS filed on 07/14/2023) and Blazej et al. (US Patent Application Publication 2015/0218553 A1; cited on IDS filed on 07/14/2023).
14. Claims 1-4, 6-9, and 14-15 are drawn to a cell comprising a first fusion protein comprising a first peptide tag and a second peptide tag; a second fusion protein comprising a first portion of a split reporter and a first affinity agent that specifically binds to the first peptide tag; and a third fusion protein comprising a second portion of the split reporter and a second affinity agent that specifically binds to the second peptide tag, wherein the first portion of the split reporter and the second portion of the split reporter produce a first signal when in proximity and are inactive when separate.
Claim 29 is drawn to a cell comprising: a first fusion protein comprising a first peptide tag; a second fusion protein comprising a second peptide tag; a third fusion protein comprising a first portion of a split reporter and a first affinity agent that specifically binds to the first peptide tag; and a fourth fusion protein comprising a second portion of the split reporter and a second affinity agent that specifically binds to the second peptide tag.
Claims 43 and 45 are drawn to a cell expressing or comprising: a first fusion protein comprising a first portion of a split reporter and a first affinity agent that specifically binds to a first peptide tag; and a second fusion protein comprising a second portion of the split reporter and a second affinity agent that specifically binds to a second peptide tag, wherein the first portion of the split reporter and the second portion of the split reporter produces a signal when in proximity and inactive when separate.
15. With respect to claim 1, Moustaqil et al. teach a first fusion protein comprising a first peptide tag (GFP) and a second peptide tag (mCherry) heterodimer fusion protein, a second fusion protein comprising a first portion of a split reporter and a first affinity agent that specifically binds to the first peptide tag (NB-GFP) linked to a luciferase (split reporter) and a third fusion protein comprising a second portion of the split reporter and a second affinity agent that specifically binds to the second peptide tag linked to a luciferase, wherein the first portion of the split reporter and the second portion of the split reporter produce a first signal when in proximity and are inactive when separate [see Abstract; p. 3, Figure 1].
With respect to claim 6, Moustaqil et al. teach wherein the first portion of the split reporter is an amino terminal portion of the split reporter and the first affinity agent is linked to the amino terminal side of the first portion and wherein the second portion of the split reporter is a carboxyl terminal portion of the split reporter and the second affinity agent is linked to the carboxyl terminal side of the second portion [see Figure 1].
With respect to claim 7, Moustaqil et al. teach wherein the signal is fluorescence [see p. 3; Figure 1 and Figure 3].
With respect to claim 8, Moustaqil et al. teach wherein the first peptide and the second peptide tag are adjacent or linked and the amino terminus [see Figure 1].
With respect to claim 9, Moustaqil et al. teach wherein the first peptide tag and the second peptide tag are adjacent or linked at the carboxyl terminus [see Figure 1].
With respect to claim 15, Moustaqil et al. teach further comprising a fourth fusion protein comprising a third peptide tag and a fourth peptide tag; a fifth fusion protein comprising a first portion of a second split reporter and a third affinity agent that specifically binds to the third peptide tag; and a sixth fusion protein comprising a second portion of the second split reporter and a fourth affinity agent that specifically binds to the fourth peptide tag, wherein the first portion of the second split reporter and the second portion of the second split reporter produce a signal, distinguishable from the signal of the split reporter of claim 1, wherein in proximity and are inactive when separate [see Abstract; p. 3, Figure 1].
With respect to claim 29, Moustaqil et al. teach a first fusion protein comprising a first peptide tag (GFP), a second fusion protein comprising a second peptide tag; a third fusion protein comprising a first portion of a split reporter and a first affinity agent that specifically binds to the first peptide tag; and a fourth fusion protein comprising a second portion of the split reporter and a second affinity agent that specifically binds to the second peptide tag [see Abstract; p. 3; Figure 1].
With respect to claim 43, Moustaqil et al. teach a first fusion protein comprising a first portion of a split reporter and a first affinity agent that specifically binds to a first peptide tag; and a second fusion protein comprising a second portion of the split reporter and a second affinity agent that specifically binds to a second peptide tag, wherein the first portion of the split reporter and the second portion of the split reporter produces a signal when in proximity and are inactive when separate [see Abstract; p. 3; Figure 1].
With respect to claim 45, Moustaqil et al. teach wherein the first portion of the split reporter is an amino terminal portion of the split reporter and the first affinity agent is linked to the amino terminal side of the first portion and wherein the second portion of the split reporter is a carboxyl terminal portion of the split reporter and the second affinity agent is linked to the carboxyl terminal side of the second portion [see Figure 1].
However, Moustaqil et al. does not teach a cell comprising the fusion proteins; wherein the peptide tags are each less than 30, 25, 20, 15, or 10 amino acids; linker of fewer than 15 amino acids; and a fourth fusion comprising a GFP11, a fifth fusion comprising GFP1-10.
McConnel et al. teach the introduction of fusion signal proteins into cells comprising peptide tags and linkers less than 15 amino acids for the sensitive detection of multiple analytes wherein the reporter signals can be altered in such a way that can be distinguished from each other [see Abstract; p. 15; p. 72].
Blazej et al. teach host cells comprising fusion proteins comprising a first and second peptide tag and a polypeptide affinity tag; a second fusion protein comprising a first portion of a split reporter complementation with GFP11 and GFP1-10 and a first affinity agent that specifically binds to the first peptide tag [see Abstract; paragraphs 0014-0015; 0023].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Moustaqil et al., McConnel et al., and Blazej et al. to express the fusion protein of Moustaqil et al. in a cell because Moustaqil et al. teach the study of protein-protein interactions using fluorescently labeled fusion proteins in a split reporter system. Both McConnel et al. and Blazej et al. teach similar systems in host cells that provide for the sensitive detection of multiple analytes in a distinguishable fashion. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Moustaqil et al., McConnel et al., and Blazej et al. because both McConnel et al. and Blazej et al. acknowledge the ability to express split reporter systems in a host cell. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
16. Claims 5 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Moustaqil et al. (International Journal of Molecular Sciences, 2017; cited on IDS filed on 07/14/2023) in view of McConnel et al. (AU 2007200365 A1; cited on IDS filed on 07/14/2023) and Blazej et al. (US Patent Application Publication 2015/0218553 A1; cited on IDS filed on 07/14/2023) as applied to claims 1-4, 6-9, 14-15, 29, 43, and 45 above, and further in view of Forment et al. (WO 2015/017313 A2; cited on IDS filed on 07/14/2023).
17. The relevant teachings of Moustaqil et al., McConnel et al. and Blazej et al. as applied to claims 1-4, 6-9, 14-15, 29, 43 and 45 are set forth above.
With respect to claims 5 and 44, the combination of Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system.
However, the combination of Moustaqil et al., McConnel et al. and Blazej et al. do not teach the cell of claims 5 and 44 wherein the split reporter is a HaloTag reporter.
Forment et al. teach HaloTag reporter systems for measuring or quantifying cell surface translocation of proteins by fluorescence [see paragraphs 0014, 0115].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Moustaqil et al., McConnel et al., Blazej et al., and Forment et al. according to the teachings of Forment et al. to use a HaloTag reporter system in the systems of Moustaqil et al., McConnel et al. and Blazej et al. because Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system using fluorescence. Forment et al. teach HaloTag reporter systems for measuring or quantifying cell surface translocation of proteins by fluorescence. It would require simple substitution of one fluorescent reporter for another for one of ordinary skill in the art to choose a HaloTag reporter system because Forment et al. acknowledges HaloTag as a way to detect and quantify protein interactions within a cell. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
18. Claims 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Moustaqil et al. (International Journal of Molecular Sciences, 2017; cited on IDS filed on 07/14/2023) in view of McConnel et al. (AU 2007200365 A1; cited on IDS filed on 07/14/2023) and Blazej et al. (US Patent Application Publication 2015/0218553 A1; cited on IDS filed on 07/14/2023) as applied to claims 1-4, 6-9, 14-15, 29, 43, and 45 above, and further in view of Zakeri et al. (PNAS, 2012; cited on IDS filed on 07/14/2023).
19. The relevant teachings of Moustaqil et al., McConnel et al. and Blazej et al. as applied to claims 1-4, 6-9, 14-15, 29, 43 and 45 are set forth above.
With respect to claims 10-11, the combination of Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system, and Blazej et al. teach host cells comprising fusion proteins comprising a first and second peptide tag and a polypeptide affinity tag; a second fusion protein comprising a first portion of a split reporter complementation with GFP11 and GFP1-10 and a first affinity agent that specifically binds to the first peptide tag [see Abstract; paragraphs 0014-0015; 0023].
However, the combination of Moustaqil et al., McConnel et al. and Blazej et al. do not teach the cell of claims 10 and 11 wherein the second tag is SpyTag and second affinity agent is SpyCatcher.
Zakeri et al. teach that peptide tags are a central tool in molecular biology in studying protein-protein interactions [see p. E695, column 1] and teach that the peptide tags SpyCatcher and SpyTag provide flexibility of reaction conditions, specificity in cells, and high yield of reaction in comparison to existing chemical biology approaches for irreversible protein targeting [see Abstract; p. E695, column 2].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Moustaqil et al., McConnel et al., Blazej et al., and Zakeri et al. according to the teachings of Zakeri et al. to use a SpyTag/SpyCatcher tag in the system of Moustaqil et al., McConnel et al. and Blazej et al. because Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system for measuring and monitoring protein-protein interactions. Zakeri et al. teach that SpyTag provide flexibility of reaction conditions, specificity in cells, and high yield of reaction in comparison to existing chemical biology approaches for irreversible protein targeting. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would have been motivated to combine the teachings of Moustaqil et al., McConnel et al., Blazej et al., and Zakeri et al. because Zakeri et al. acknowledges that SpyTag provide flexibility of reaction conditions, specificity in cells, and high yield of reaction in comparison to existing chemical biology approaches for irreversible protein targeting. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
20. Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Moustaqil et al. (International Journal of Molecular Sciences, 2017; cited on IDS filed on 07/14/2023) in view of McConnel et al. (AU 2007200365 A1; cited on IDS filed on 07/14/2023) and Blazej et al. (US Patent Application Publication 2015/0218553 A1; cited on IDS filed on 07/14/2023) as applied to claims 1-4, 6-9, 14-15, 29, 43, and 45 above, and further in view of Zakeri et al. (PNAS, 2012; cited on IDS filed on 07/14/2023) and Gotzke et al. (Nature Communications, 2019; cited on IDS filed on 03/25/2026).
21. With respect to claim 12, the combination of Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system, and Blazej et al. teach host cells comprising fusion proteins comprising a first and second peptide tag and a polypeptide affinity tag; a second fusion protein comprising a first portion of a split reporter complementation with GFP11 and GFP1-10 and a first affinity agent that specifically binds to the first peptide tag [see Abstract; paragraphs 0014-0015; 0023].
However, the combination of Moustaqil et al., McConnel et al. and Blazej et al. do not teach the cell of claim 12 wherein the first tag is ALFA-tag and the first affinity agent is NbALFA, and the second tag is SpyTag and second affinity agent is SpyCatcher.
Zakeri et al. teach that peptide tags are a central tool in molecular biology in studying protein-protein interactions [see p. E695, column 1] and teach that the peptide tags SpyCatcher and SpyTag provide flexibility of reaction conditions, specificity in cells, and high yield of reaction in comparison to existing chemical biology approaches for irreversible protein targeting [see Abstract; p. E695, column 2].
Gotzke et al. teach that specialized epitope tags are widely used for detecting, manipulating or purifying proteins and teach a nanobody NbALFA that binds ALFA tagged proteins with low picomolar affinity that is suitable for super-resolution microscopy, immunoprecipitations, Western Blotting and in vivo detection of proteins [see Abstract].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Moustaqil et al., McConnel et al., Blazej et al., Zakeri et al., and Gotzke et al. according to the teachings of Zakeri et al. and Gotzke et al. to use a SpyTag/SpyCatcher tag and ALFA-tag/NbALFA tags in the system of Moustaqil et al., McConnel et al. and Blazej et al. because Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system for measuring and monitoring protein-protein interactions. Zakeri et al. teach that SpyTag provide flexibility of reaction conditions, specificity in cells, and high yield of reaction in comparison to existing chemical biology approaches for irreversible protein targeting. Gotzke et al. teach that specialized epitope tags are widely used for detecting, manipulating or purifying proteins and teach a nanobody NbALFA that binds ALFA tagged proteins with low picomolar affinity that is suitable for super-resolution microscopy, immunoprecipitations, Western Blotting and in vivo detection of proteins. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would have been motivated to combine the teachings of Moustaqil et al., McConnel et al., Blazej et al., Zakeri et al., and Gotzke et al. because Zakeri et al. acknowledges that SpyTag provide flexibility of reaction conditions, specificity in cells, and high yield of reaction in comparison to existing chemical biology approaches for irreversible protein targeting, and Gotzke et al. acknowledges that specialized epitope tags are widely used for detecting, manipulating or purifying proteins and teach a nanobody NbALFA that binds ALFA tagged proteins with low picomolar affinity that is suitable for super-resolution microscopy, immunoprecipitations, Western Blotting and in vivo detection of proteins. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
22. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Moustaqil et al. (International Journal of Molecular Sciences, 2017; cited on IDS filed on 07/14/2023) in view of McConnel et al. (AU 2007200365 A1; cited on IDS filed on 07/14/2023) and Blazej et al. (US Patent Application Publication 2015/0218553 A1; cited on IDS filed on 07/14/2023) as applied to claims 1-4, 6-9, 14-15, 29, 43, and 45 above, and further in view of Zakeri et al. (PNAS, 2012; cited on IDS filed on 07/14/2023) and Gotzke et al. (Nature Communications, 2019; cited on IDS filed on 03/25/2026).
23. With respect to claim 13, the combination of Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system, and Blazej et al. teach host cells comprising fusion proteins comprising a first and second peptide tag and a polypeptide affinity tag; a second fusion protein comprising a first portion of a split reporter complementation with GFP11 and GFP1-10 and a first affinity agent that specifically binds to the first peptide tag [see Abstract; paragraphs 0014-0015; 0023].
However, the combination of Moustaqil et al., McConnel et al. and Blazej et al. do not teach the cell of claim 13 wherein the second tag is ALFA-tag and the second affinity agent is NbALFA.
Gotzke et al. teach that specialized epitope tags are widely used for detecting, manipulating or purifying proteins and teach a nanobody NbALFA that binds ALFA tagged proteins with low picomolar affinity that is suitable for super-resolution microscopy, immunoprecipitations, Western Blotting and in vivo detection of proteins [see Abstract].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Moustaqil et al., McConnel et al., Blazej et al., and Gotzke et al. according to the teachings of Gotzke et al. to use ALFA-tag/NbALFA tags in the system of Moustaqil et al., McConnel et al. and Blazej et al. because Moustaqil et al., McConnel et al. and Blazej et al. teach a cell expressing a split reporter system for measuring and monitoring protein-protein interactions. Gotzke et al. teach that specialized epitope tags are widely used for detecting, manipulating or purifying proteins and teach a nanobody NbALFA that binds ALFA tagged proteins with low picomolar affinity that is suitable for super-resolution microscopy, immunoprecipitations, Western Blotting and in vivo detection of proteins. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would have been motivated to combine the teachings of Moustaqil et al., McConnel et al., Blazej et al., and Gotzke et al. because Gotzke et al. acknowledges that specialized epitope tags are widely used for detecting, manipulating or purifying proteins and teach a nanobody NbALFA that binds ALFA tagged proteins with low picomolar affinity that is suitable for super-resolution microscopy, immunoprecipitations, Western Blotting and in vivo detection of proteins. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
24. Status of the claims:
Claims 1-15, 29, and 42-45 pending.
Claim 42 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 1-15, 29 and 43-45 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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