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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/06/2026 has been entered.
Application status
In response to the previous Office action, a Final rejection (mailed on 09/10/2025), Applicants filed a response and amendment received on 02/06/2026. Said amendment canceled Claims 2 and 7-11, amended Claim 1, and added claim 22. Thus, Claims 1, 3-6, 12 and 21-22 are at issue and present for examination.
It is noted by the Examiner that Claims 13-20 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention in the previous Office actions, a non-Final rejection (mailed on 04/22/2025).
Claim Rejections - 35 U.S.C. § 112
Claim 22 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 22 recites “a composition of matter comprising a fusion protein attached to the outer surface of a synthetic lipid particle, wherein the fusion protein comprises a light-generating protein and a light-transducing protein, wherein said light-generating protein is proximal to the outer surface of the particle and said light-transducing protein is distal to the outer surface of the particle” which is new matter. The instant specification does not describe the positioning of the light-generating protein and a light-transducing protein with respect to the outer surface of a synthetic lipid particle, and the sections of the specification pointed out by Applicants, i.e., page 23, lines 10-111 and page 24, line 14 (see the last paragraph of page 1 of Applicants’ argument) do not provide any support for claim 22.
Claim Rejections - 35 U.S.C. § 103 - MAINTAINED
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 previous rejection of Claim 1, 3-6 and 12 under 35 U.S.C. 103 as being unpatentable over Berglund et al. (Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation, PNAS, 113 (3) E358-E367, published on 01/05/2016) in view of Parag-Sharma et al. (ACS Synth Biol. 2020 January 17; 9(1): 1–9), Tischer (Using optogenetic tools to test the kinetic proofreading model of T cell receptor ligand discrimination, Dissertation, 2017), and an evidentiary reference of Berglund et al. ("Light-Emitting Channelrhodopsin for Combined Optogenetic and Chemical-Genetic Control of Neurons", PLOS ONE, 8(3): e59759-1 - e59759-11, 27 March 2013, see IDS) is maintained.
The instant claims are drawn to a composition of matter comprising a fusion protein attached to the outer surface of a synthetic lipid particle comprising a nickel chelating lipid, wherein the fusion protein comprises a light-generating protein and a light-transducing protein, wherein said light-generating protein is attached to the nickel chelating lipid.
Berglund et al. teach various fusion proteins comprising wild-type Gaussia luciferase (GLuc) or GLuc variants (i.e., light-generating protein) fused to Volvox channelrhodopsin 1 (VChR1) (i.e., light-transducing protein), more specifically to the extracellular N terminus of VChR1, which makes said fusion proteins to be lipidated and be expressed on the extracellular surface of transfected HEK cells because VChR1 comprises a cell membrane targeting domain, allowing said fusion protein to be expressed and be translocated to cell membrane (see Abstract; p.359, left column under “Identifying a GLuc Variant That Emits More Light”; Fig. 4. A & D on p. E362).
Claims 3-4 are included in this rejection because Berglund et al. teach that GLuc is inducible light-generating protein as it is dose-dependently induced to bioluminescence by coelenterazine (CTZ) (see Fig.1 C on pg. E359).
Claim 6 is included in this rejection because GLuc is attached to the N-terminus of ChR2 through a flexible 15 amino-acid linker (see the evidentiary reference of Berglund et al. on page 2, last sentence in left column continued to next column).
Berglund et al. do not teach the use of iLID as a light-transducing protein, the use of nickel chelating lipid, and light-generating protein that comprises a histidine tag.
Parag-Sharma et al. a bioluminescence resonance energy transfer (BRET)-activated optogenetics (BEACON), wherein iLID is activated upon bioluminescence of CeNLuc (a fusion of NanoLuc in-frame with a cyan fluorescent protein) which produces ~474 nm (blue-green light) (see Abstract; p. 4, 2nd para; p. 5, 3rd para).
Tischer teach the use of optogenetic system comprising LOVTRAP-based light-responsive protein-protein interactions on a supported lipid bilayer (SLB) containing nickel chelating lipids or Ni-NTA containing bilayers (see page 72).
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the claimed invention to make and use the composition comprising the fusion protein taught by Berglund et al. and replace the light-transducing protein VChR 1 with iLID as taught by Parag-Sharma et al. while using the nickel chelating lipids with said fusion protein comprising a histidine tag taught as taught by Tischer. A POSITA would have been motivated to make and use such composition especially because [1] GLuc produces a blue light (see p. E365, left column, 3rd para of Berglund et al.) which can be used to activate iLID, which is an optimal light-transducing protein for the purposes of BEACON as taught by Parag-Sharma et al., [2] GLuc is much simpler to make (only 169 amino acids long) than CeNLuc, which is a fusion of NanoLuc in-frame with a cyan fluorescent protein, as a light-generating fusion partner, and [3] Tischer describes a standard attachment method for proteins to NiNTA containing lipid bilayer which can be routinely performed on page 55, especially for ‘optimizing photoactivation and photoreversion rates, wavelengths for photoswitching” (see page 28). A POSITA would have had a reasonable expectation of success to make and use such composition because all of the required biochemical reagents and techniques were readily available and rampantly used as evidenced by Berglund et al., Parag-Sharma et al. and Tischer prior to the filing of the instant application.
It is noted by the Examiner the newly added limitation of claim 1, “wherein said light-generating protein is attached to the nickel chelating lipid” is inherently met by the teachings of the prior art references of Berglund et al., Parag-Sharma et al. and Tischer because the light-generating protein is part of the fusion protein which is attached to the nickel chelating lipid.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Applicants’ Arguments:
Applicant argues that the claimed configuration of the light-responsive protein (e.g., iLID) at the distal end of the fusion protein architecture provides significant and unexpected advantages that would not have been suggested by the prior art.
Specifically, positioning iLID distally reduces steric hindrance, thereby enhancing its conformational flexibility and functional responsiveness upon illumination. This structural arrangement facilitates more efficient exposure of the buried peptide epitope (e.g., SsrA), which is normally concealed within the iLID domain but becomes accessible upon light activation. This exposure allows for high-affinity binding to its cognate partner (e.g., SspB), which may be in solution, either freely or fused to a targeting moiety, or immobilized on another particle or cell surface.
The distal positioning enables unobstructed movement and optimized binding kinetics, features that are functionally compromised in more centrally located or membrane-tethered configurations, as taught in the cited references. Notably, none of the cited references, including Berglund et al. or Parag-Sharma et al., teach or suggest a design wherein the photodimerizing domain is placed distally with the light- generating domain membrane-bound, nor do they disclose or predict the performance advantages arising from such spatial separation of components.
Furthermore, while iLID is used as an illustrative embodiment, the invention is not limited thereto. The key structural and functional insight lies in placing the light- responsive module in a sterically permissive, distal position that permits photoinduced epitope exposure and downstream selective binding interactions. This modular and spatially optimized arrangement enables novel utility for targeting and anchoring applications that require precise spatial and temporal control, such as in targeted therapeutic delivery, biosensing, or synthetic cell-to-cell communication systems.
Examiner’s Explanation:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. Any arguments regarding the positioning of the light-generating protein and a light-transducing protein with respect to the outer surface of a synthetic lipid particle as recited in claim 22 is moot because the instant rejection does not include claim 22 (see above 112(a) rejection under new matter). For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of prior art.
Allowable
Claim 21 is indicated to be allowable if claim 21 is written as an independent claim (currently claim 21 depends from a rejected claim 1). It is noted by the Examiner that claim 21 has the same language as previously proposed in the Examiner’s amendment for allowance (see interview summary dated 04/22/2025).
Conclusion
Claims 1, 3-6 and 22 are rejected for the reasons as stated above. Claim 21 is indicated to be allowable if claim 21 is written as an independent claim (currently claim 21 depends from a rejected claim 1). Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
The instant Office action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (5712720939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656