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 .
Claims Status
Claims 3-20 are canceled.
Claims 1-2 and 21-35 are pending.
Election/Restrictions
Applicant’s election without traverse of Invention I (claims 1-2) in the reply filed on 09/10/2026 is acknowledged. Applicant has added new claims 21-35. The Examiner has rejoined new claims 21-35 into Invention I.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/15/2025 is acknowledged. The submission is in compliance with the provision of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. (See Drawing, Fig. 26A, Fig 26B, and Fig. 26C).
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see specification paragraphs 0137, 0152, and 0177). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 objected to because of the following informalities: Claim 1 recites “90% identical to positions 40-267 of an amino acid sequence identified at SEQ ID NO: 1”. The terminology used “at SEQ ID NO: 1” is odd. Appropriate correction is required.
Claims 25-30 are objected to because they are dependent on rejected claims. Appropriate correction is required.
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, 2, and 21-24 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.
With regards to claim 1, it is unclear how a luciferase “defines an amino acid sequence”. How is defining interpreted? The specification does not really help clarify “defining”. In the interest of compact prosecution, the Examiner is interpreting “defining” as the luciferase comprising the amino acid sequence.
With regards to claim 1, there is a question of is the “transgenic organism” transgenic before the luciferase nucleic acid is incorporated or after? In the interest of compact prosecution, the Examiner is interpreting the organism to be transgenic after incorporation of the isolated nucleic acid.
With regards to claim 2, the claim recites “wherein the luciferase defines an amino acid sequence”. It is unclear how a luciferase defines an amino acid sequence. The specification does not help clarify “defining”. In the interest of compact prosecution, the Examiner is interpreting the claim as the luciferase comprising the amino acid sequence.
With regards to claims 21-24, it is unclear how claims 21-24 further limit claim 1 from which they depend. Are not each of the substitutions relative to SEQ ID NO. 1? If not, then what are they relevant to? In the interest of compact prosecution, the Examiner is interpretating the claims to have the amino acid substitutions in SEQ ID NO:1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 21, and 31-35 are rejected under 35 U.S.C. 103 as being unpatentable over Khakhar et al. (eLife, Vol. 9:e52786; published March 25, 2020), hereinafter referred to as Khakhar, in view of UnitPro Database entry: (A0A3G9K9H1_9AGAR; first entry February 13, 2019), hereinafter referred to as 9AGAR, and further in view of Tong et al (Journal of Biological Chemistry, Vol. 295, pg. 16013-16022; published 2020), hereinafter referred to as Tong.
With regards to claims 1, 21, 31 and 33-34, Khakhar teaches a method of producing bioluminescence across various tissues in a broad range of plants (see Abstract, pg. 1). Khakhar teaches the insertion of genes that encode the enzymes of the fungal bioluminescence pathway (FBP) into tobacco plants (see Introduction, pg. 2). Khakhar teaches that auto-luminescent plants could be created by integrating expression cassettes for the three enzymes in the biosynthesis pathway, NPGA, H3H, and Hisps, the recycling pathway, CPH, and the fungal luciferase Luz.(see pg. 3, last paragraph). Khakhar teaches that the fungal bioluminescence pathway (FBP) creates auto-luminescence when transiently expressed. Khakhar teaches the schematic of the chemical reactions driving the generation of auto-luminescence in planta (see Figure 1, panel A, pg. 4). Khakhar teaches that caffeic acid produced by the phenylpropanoid biosynthesis pathway is converted to Hispidin by Hisps once it is post-translationally activated by NPGA. Khakhar teaches that hispidin is then converted to 3-hydroxyhispidin, the luciferin molecule, by H3H. Khakhar teaches that finally, the luciferase Luz oxidizes 3-hydroxyhispidin (in the presence of molecular oxygen O2) into a high energy intermediate which degrades into Caffeylpyruvic acid, producing light (see Figure 1, panel A, pg. 4, also see figure below).
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Khakhar teaches the reconstitution of the fungal bioluminescence pathway into the leaves of Nicotiana benthamiana (see pg. pg. 3, first paragraph).
With regards to claim 32, Khakhar teaches that while N. benthamiana is an excellent model for prototoyping, Khakhar teaches that the fungal bioluminescence pathway should work in any plant species as long as appropriate promoters and terminators are used to express the pathway enzymes and as caffeic acid is ubiquitous in higher plants (see pg. 5, last paragraph). Khakhar teaches the agrobacterium infiltrations with the fungal bioluminescence pathway of petals from Petunia hybrida which resulted in auto-luminescence in all flowers with a range of intensities (see pg. 5, last paragraph).
With regards to claim 35, Khakhar teaches an image in the dark with an eight minute exposure of a N. benthamiana leaf infiltrated with the fungal bioluminescence pathway demonstrating auto-luminescence in the infiltrated zone (detection of bioluminescence by visual inspection) (See Figure 1, panel B, and see figure below).
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With regards to clams 1 and 21, Khakhar does not teach that the luciferase is encoded by a nucleic acid defining an amino acid sequence at least 90% identical to the positions 40-267 of an amino acid sequence identified at SEQ ID NO: 1 of the current instant application, the amino acid sequence comprising at least one amino acid substitution selected from T99P, T192S, A199P.
However, 9AGAR teaches a fungal luciferase from Neonothopanus gardneri that shares 90.4% with SEQ ID NO: 1 of the current instant application and comprises a T99P amino acid substitution (see sequence alignment and underlined residue below).
Query Match 90.4%; Score 1253; Length 264;
Best Local Similarity 90.8%;
Matches 236; Conservative 12; Mismatches 12; Indels 0; Gaps 0;
Qy 5 ISLSSLFERLSKLSSRSIAITCGVVLASAIA FPIIRRDYQTFLEVGPSYAPQNFRGYIIV 64
::| | :||| ||||||||| |||||||||| ||||||||||||||||||||||||||
Db 1 MNLPSFVQRLSTASSRSIAITCVVVLASAIA FPFIRRDYQTFLEVGPSYAPQNFRGYIIV 60
Qy 65 CVLSLFRQEQKGLAIYDRLPEKRRWLADLPFREGTRPSITSHIIQRQRTQLVDQEFATRE 124
||||||||||||| ||||||||||||:|||||:| |||||||||||||||||| :|||:|
Db 61 CVLSLFRQEQKGLEIYDRLPEKRRWLSDLPFRDGPRPSITSHIIQRQRTQLVDPDFATQE 120
Qy 125 LIDKVIPRVQARHTDKTFLSTSKFEFHAKAIFLLPSIPINDPLNIPSHDTVRRTKREIAH 184
|| |||||||||||||||||||||||||||||||||||||||||:|||||||||||||||
Db 121 LIGKVIPRVQARHTDKTFLSTSKFEFHAKAIFLLPSIPINDPLNVPSHDTVRRTKREIAH 180
Qy 185 MHDYHDCTLHLALAAQDGKEVLKKGWGQRHPLAGPGVPGPPTEWTFLYAPRNEEEARVVE 244
||||||||||:|||||||||||||||||||||||||||||||||||||||||||| ||||
Db 181 MHDYHDCTLHIALAAQDGKEVLKKGWGQRHPLAGPGVPGPPTEWTFLYAPRNEEEVRVVE 240
Qy 245 MIVEASIGYMTNDPAGKIVE 264
||:||:|||||||||||:||
Db 241 MIIEAAIGYMTNDPAGKVVE 260
9AGAR further shares 94.7% sequence identity with positions 40-267 of SEQ ID NO:1 of the current instant application (see sequence alignment below).
Alignment over residues 40-267:
RESULT 1
AASEQ2_09182026_134728
Query Match 94.7%; Score 1143; DB 1; Length 260;
Best Local Similarity 93.8%;
Matches 211; Conservative 9; Mismatches 5; Indels 0; Gaps 0;
Qy 40 RRDYQTFLEVGPSYAPQNFRGYIIVCVLSLFRQEQKGLAIYDRLPEKRRWLADLPFREGT 99
|||||||||||||||||||||||||||||||||||||| ||||||||||||:|||||:|
Db 36 RRDYQTFLEVGPSYAPQNFRGYIIVCVLSLFRQEQKGLEIYDRLPEKRRWLSDLPFRDGP 95
Qy 100 RPSITSHIIQRQRTQLVDQEFATRELIDKVIPRVQARHTDKTFLSTSKFEFHAKAIFLLP 159
|||||||||||||||||| :|||:||| ||||||||||||||||||||||||||||||||
Db 96 RPSITSHIIQRQRTQLVDPDFATQELIGKVIPRVQARHTDKTFLSTSKFEFHAKAIFLLP 155
Qy 160 SIPINDPLNIPSHDTVRRTKREIAHMHDYHDCTLHLALAAQDGKEVLKKGWGQRHPLAGP 219
|||||||||:|||||||||||||||||||||||||:||||||||||||||||||||||||
Db 156 SIPINDPLNVPSHDTVRRTKREIAHMHDYHDCTLHIALAAQDGKEVLKKGWGQRHPLAGP 215
Qy 220 GVPGPPTEWTFLYAPRNEEEARVVEMIVEASIGYMTNDPAGKIVE 264
|||||||||||||||||||| ||||||:||:|||||||||||:||
Db 216 GVPGPPTEWTFLYAPRNEEEVRVVEMIIEAAIGYMTNDPAGKVVE 260
Furthermore, Tong teaches that the fungal luminescence mechanism involves a luciferase which oxidizes 3-hydroxyhispidin (luciferin) into a high energy intermediate and that all luminescent fungi share the same luciferin/luciferase system (see pg. 16013).
It would have been obvious to one of ordinary skill in the art of protein engineering to modify the method of producing bioluminescence taught by Khakhar by substituting the Luz luciferase taught by Khakhar in the fungal bioluminescence pathway with the fungal Neonothopanus gardneri luciferase taught by 9AGAR. One of ordinary skill in the art would find motivation to do so from the teachings of 9AGAR who discloses a fungal luciferase with high sequence identity to SEQ ID NO: 1 of the current instant application and from the teachings of Tong who teaches that all luminescent fungi share the same luciferase/luciferase system. One of ordinary skill in the art would expect that due to the high sequence identity, the fungal Neonothapanus gardneri luciferase would serve as a suitable enzyme with inherent luciferase activity in the fungal bioluminescence pathway taught by Khakhar and Tong. One of ordinary skill in the art would have expectations of success in doing so from the combined teachings of Khakhar, 9AGAR, and Tong who provide all the necessary teachings, reagents, and methods to do so.
Therefore, claims 1, 21, and 31-35 are rejected under 35 U.S.C. 103 as being unpatentable over Khakhar et al. (eLife, Vol. 9:e52786; published March 25, 2020) in view of UnitPro Database entry: (A0A3G9K9H1_9AGAR; first entry February 13, 2019) and further in view of Tong et al (Journal of Biological Chemistry, Vol. 295, pg. 16013-16022; published 2020).
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Li et al. “Glowing plants can light up the night sky? A review” Biotechnology Bioengineering, Vol. 118, pg. 3706-3715; published 2021.
Rueter et al. “Lighting the Way: Advances in Engineering Autoluminescent Plants” Trends in Plant Science, Vol. 25, pg. 1176-1179; published December 2020.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE T LOUNTOS whose telephone number is (571)272-0502. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached at 408-918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GEORGE THEMISTOCLIS LOUNTOS/ Examiner, Art Unit 1652
/ROBERT B MONDESI/ Supervisory Patent Examiner, Art Unit 1652
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