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 .
Priority
Applicant has not filed a certified copy of the foreign priority application although being notified.
Status of Claims
The amendments submitted on May 29th, 2026, have been entered.
Claims 1-18 are pending.
Claims 1-10 are examined herein.
The text of those sections of Title 35 U.S. Code, not included in this action, can be found in a prior Office action.
Claim Interpretation
Claim 1 recites that the transgenic plant comprises fungal luciferin in the plant cells. In the Applicant Arguments/Remarks Made in an Amendment filed 05/29/2026, the Applicant asserts that the plain language of claim 1 allows fungal luciferin to be present in the cells by the broadest reasonable language, including endogenous biosynthesis [Id. pg. 7, paragraph 3]. The Office agrees.
Withdrawn Objections and Rejections
The objection to the Specification is withdrawn in light of Applicant’s amendments to the claim.
The rejections of claims 1, 2, and 7-10 under 35 USC § 103 are withdrawn in light of Applicant’s amendments to the claims to recite the luciferase having an amino acid sequence at least 90% identical to that of SEQ ID NO: 2.
Maintained Rejections
Claim Rejections - 35 USC § 112(a) – Written Description
Claims 1-10 are 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.
The claims are broadly drawn to a bioluminescent transgenic plant comprising a luciferase with SEQ ID NO. 2 having the ability to oxidize a molecule selected from a group consisting of fungal luciferin molecules, wherein the transgenic plant comprises fungal luciferin in the plant cells and biosynthesizes the fungal luciferin. The claims require a transgenic plant with the ability to biosynthesize fungal luciferin, yet the instant specification describes only the coding sequence of luciferase from Neonothopanus nambi optimized for expression in Physcomitrella patens moss cells soaked in 3-hydoxyhispidin substrate (Example 13). The broadness of claim 1 includes wherein the transgenic plant has the ability to biosynthesize fungal luciferin.
The level of skill and knowledge at the time of filing was such that creation of transgenic plants comprising optimized fungal luciferase sequences and fungal luciferin, wherein the plant is bioluminescent and has the ability to biosynthesize fungal luciferin within the plant’s cells, required additional steps not disclosed in the instant specification. Research published post-filing (of the foreign priority Russian application RU2017102986) with the author of the instant application, Ilia Yampolsky, conceded that future work should focus on finding the genes responsible for 3-hydroxyhispidin biosynthesis and expressing these genes in a transgenic plant with fungal luciferase (Guglya et al., 2017).
A later publication with the same common inventor disclosed autoluminescent plants engineered with a fungal bioluminescence system that converts caffeic acid into luciferin with integration of fungal bioluminescence genes (Mitiouchkina et al., 2020). The instant specification does not describe the potential for caffeic acid conversion to luciferin within a transgenic plant. The instant specification additionally does not describe biosynthesis of fungal luciferin or divulge any mechanism to achieve biosynthesis of luciferin within plant cells other than stating, “genetically modified plants may serve as light sources when 3-hydroxyhispidin or related molecules are added to the medium or soil, or autonomously bioluminese if 3-hydroxyhispidin biosynthesis occurs in the host cells (¶ 0115).” The mechanism for introducing the fungal luciferin 3-hydroxyhispidin was soaking in BCD medium containing 3-hydoxyhispidin at a concentration of 660 µg/ml and the instant specification states that 3-hydroxyhispidin is a membrane permeant molecule (¶ 013). The specification further discloses that in visualization of cancer cell migration in animal cells, the subject luciferases can be visualized in vivo in living organisms without tissue fixation and permeabilization since 3-hydroxyhispidin is capable of penetrating through cell membranes (¶ 0115). As such, it is assumed that the system comprising fungal luciferin in the plant cells is through the cell membrane and not through biosynthesis within the host plant cell as claimed.
Therefore, given the lack of reduction to practice in the specification with regard to the structural and functional characteristics of the plant’s ability to biosynthesize the fungal luciferin 3-hydroxyhispidin, or any other fungal luciferin, Applicant does not appear to have been in possession of the claimed plant at the time this application was filed.
Response to Applicant’s Arguments:
The Applicant’s arguments in the response submitted May 29th, 2026 have been carefully considered but were not found persuasive with regard to rejection of claims 1-10 under 35 USC § 112(a).
Applicant argues that the Specification provides support for a transgenic plant with the ability to biosynthesize fungal luciferin, reciting that the plant “may autonomously bioluminesce if 3-hydroxyhispidin biosynthesis occurs in the host cells.” [Applicant Arguments/Remarks Made in an Amendment filed 05/29/2026; pg. 7, ¶1-3]. Applicant contends that the hispidin-3-hydroxylase enzyme was already known in the art and available to one of ordinary skill in the art to isolate and express a gene encoding the recombinant enzyme [Id. pg. 7, ¶4]. Applicant further argues that the Specification teaches how to make the claimed transgenic plants in several places, specifically teaching light-emitting transgenic moss [Id. pg. 8, second paragraph down].
As stated in the Office action filed 12/29/2025, the Applicant broadly claims a bioluminescent transgenic plant comprising a luciferase with SEQ ID NO. 2 having the ability to oxidize a molecule selected from a group consisting of fungal luciferin molecules, wherein the transgenic plant comprises fungal luciferin in the plant cells and biosynthesizes the fungal luciferin, thus, requiring that the transgenic plant has the ability to biosynthesize fungal luciferin. However, the instant Specification describes only the coding sequence of luciferase from Neonothopanus nambi optimized for expression in Physcomitrella patens moss cells soaked in 3-hydoxyhispidin substrate (Example 13).
Applicant states that the Specification provides support at ¶0117, by reciting that “[g]enetically modified plants modified plants may serve as light sources when 3-hydroxyhispidin or related molecules are added to the medium or soil, or autonomously bioluminesce if 3-hydroxyhispidin biosynthesis occurs in the host cells." The Applicant further cites U.S. Patent 10,584,369 B2 to show that the hispidin-3-hydroxylase enzyme was already known in the art and available to one of ordinary skill and thus, it would have been routine to isolate and express a gene encoding a recombinant enzyme. However, U.S. Patent 10,584,369 B2 teaches methods and reagents for detecting luciferases in a biological sample and does not suggest that 3-hydroxyhispidin biosynthesis can occur within a host cell. Instead, U.S. Patent 10,584,369 B2 teaches that the biological samples may express recombinant luciferase or luciferase and hispidin-3-hydroxylase or their functional mutants and that the nucleic acid sequences used for expression of said proteins may be obtained from natural sources, such as higher fungi, or synthesized [¶32]. U.S. Patent 10,584,369 B2 does not suggest 3-hydroxyhispidin biosynthesis within plant cells, disclosing that host-cells such as E. coli, B. subtilis, S. cerevisiae, insect cells in combination with baculovirus vectors, or cells of a higher organism such as vertebrates, e.g., COS 7 cells, HEK 293, CHO, Xenopus oocytes, etc., may be used for production of the protein.
As pointed out in the Office action filed 12/29/2025, research published post-filing (of the foreign priority Russian application RU2017102986) with the author of the instant application, Ilia Yampolsky, conceded that future work should focus on finding the genes responsible for 3-hydroxyhispidin biosynthesis and expressing these genes in a transgenic plant with fungal luciferase (Guglya et al., 2017). This publication was published post-filing date of the U.S. Patent 10,584,369 B2, suggesting that it would not have merely been routine with the hispidin-3-hydroxylase.
Additionally, a later publication by the same common inventor teaches autoluminescent plants engineered with a fungal bioluminescence system that converts caffeic acid into luciferin with integration of fungal bioluminescence genes (Mitiouchkina et al., 2020) [see, Non-Final Rejection Office action filed 12/29/2025; pg. 6, ¶3]. Mitiouchkina teaches that, “although the metabolic pathway underlying fungal bioluminescence (the caffeic acid cycle) was recently reported, applying this to luminescent imaging in multicellular organisms had only been demonstrated with externally-supplied substrate.” [Mitiouchkina et al., 2020; pg. 2, ¶2]. This publication specifically uses DNA cassettes containing codon-optimised versions of the four previously reported Neonothopanus nambi bioluminescence genes: nnluz (luciferase), nnhisps (hispidin synthase), nnh3h (hispidin-3-hydroxylase), and nncph (caffeoyl pyruvate hydrolase) [Id. pg. 2, ¶4]. The bioluminescence genes used in this study were reported in 2018 (Kotlobay AA, et al. Proc Natl Acad Sci U S A. 2018; 115:12728–12732. [PubMed: 30478037]; incorporated herein by reference), after the effective filing date of the instant application.
The mechanism for introducing the fungal luciferin 3-hydroxyhispidin was soaking in BCD medium containing 3-hydoxyhispidin at a concentration of 660 µg/ml and the instant Specification states that 3-hydroxyhispidin is a membrane permeant molecule [see, instant Specification ¶ 013]. The Specification further discloses that in visualization of cancer cell migration in animal cells, the subject luciferases can be visualized in vivo in living organisms without tissue fixation and permeabilization since 3-hydroxyhispidin is capable of penetrating through cell membranes [Id. ¶ 0115], suggesting that the fungal luciferin the introduced to the host plant cell through the cell membrane. The Applicant does not reduce to practice any other fungal luciferin. Therefore, the Applicant has only reduced to practice exogenous application of 3-hydoxyhispidin, which was known at the time of filing as suggested by Mitiouchkina.
To satisfy the written description requirement, a patent Specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. The written description requirement may be satisfied in a number of ways, including a reduction to practice or a well-established correlation between structure and function disclosed in the art prior to the filing date.
MPEP § 2163 details that: "[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim." UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987); and “If the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function.” Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49.
In the instant case, the art prior to the filing date does not establish a strong correlation between structure and function and one skilled in the art would not reasonably predict that the structure would lead to the function. Further, the Applicant has not provided a physical embodiment that includes all limitations of the claims, providing no working examples to reduce to practice the claimed invention. Suggesting that the genetically modified plants could autonomously bioluminesce if the 3-hydroxyhispidin biosynthesis occurs in the plant host cells is not sufficient when the art at the time of filing does not suggest 3-hydroxyhispidin. The art at best suggests recombinant hispidin-3-hydroxylase in host cells that are not plant host cells and does not mention 3-hydroxyhispidin biosynthesis occurring in the host cells.
Thus, the claims fail to meet the written description requirement and the rejection under 35 USC § 112(a) is maintained.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
Claim 1-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for bioluminescent transgenic moss gametophytes, does not reasonably provide enablement for the broadly claimed genus of all possible transgenic plants. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
The claims are broadly drawn to a bioluminescent transgenic plant comprising: a luciferase having the amino acid sequence at least 90% identical to that of SEQ ID NO. 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, or 34, and the ability to oxidize a molecule selected from a group consisting of 3-hydroxyhispidin, (E)-6-(4-diethylamino)styryl)-3,4-dihydroxy-2H-pyran-2- one, (E)-3,4-dihydroxy-6-(4-hydroxystyryl)-2H-pyran-2-one, (E)-6-(2-1 H-indol-3-yl)vinyl)- 3,4-dihydroxy-2H-pyran-2-one, (E)-6-(2-(1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinoline- 9-yl)vinyl)-3,4-dihydroxy-2H-pyran-2-one, and (E)-3,4-dihydroxy-6-(2-(6- hydroxynaphthalene-2-yl)vinyl)-2H-pyran-2-one, wherein fungal luciferin is within the plant cells. Applicant elected SEQ ID NO.2.
As currently claimed, this broad genus of “transgenic plant” includes a vast array of species in which fungal luciferin and luciferase may or may not be functional to obtain a bioluminescent plant. The instant specification provides only guidance for the coding sequence of luciferase from Neonothopanus nambi optimized for expression in Physcomitrella patens moss cells soaked in 3-hydoxyhispidin substrate (Example 13). At the time of filing, transgenic plants comprising optimized fungal luciferase sequences and fungal luciferin, particularly 3-hydroxyhispidin, wherein the plant is bioluminescent and comprises the fungal luciferin within the plant’s cells, were not possible to the full scope of plants as claimed. Morath et al. discloses that the bryophyte model organism Physcomitrella patens has several advantages over other model plants and is used regularly in biotechnical applications due to its facile cultivation and ease of genetic manipulation with the ability for homologous recombination (2014). As the mechanism for introducing the fungal luciferin 3-hydroxyhispidin in the instant application was soaking in BCD medium containing 3-hydoxyhispidin at a concentration of 660 µg/ml, it is assumed that the system for the fungal luciferin being in the plant cells is through the cell membrane. While this mode of entry into the plant cells may work effectively for P. patens, allowing for the bioluminescence and signal strength claimed in this invention, there is no evidence that this would be enabled in the full scope of the claims.
Knowledge gained from studying mosses is partially translatable to vascular plants, but significant differences in their fundamental biology mean that not all findings apply universally (Turetsky et al., 2012). Mosses (bryophytes) and vascular plants (like trees and flowering plants) are distinct groups that evolved different strategies for survival on land.
3-hydroxyhispidin was identified as the luciferin that most, if not all, luminous fungal species utilize suggesting that this is suitable substrate for bioluminescence in transgenic plants (Purtov et al., 2015, final ¶). No evidence was provided in the instant specification that the listed compounds other than 3-hydroxyhispidin are capable of acting as luciferins for the subject luciferases in transgenic plants. With only one working example provided in the specification, alternate species would require significant experimentation for protocol creation, as protoplast regeneration alone is often times not reproducible across species and the effectivity of creating bioluminescent plants would be unpredictable (Jeong, et al., 2021).
As the specification does not describe obtaining transgenic plants to the full scope of all possible claimed plant species/genera/families/orders/classes, undue trial and error and experimentation would be required to develop such a method and the tools required for it, if such methods are even obtainable.
Given the claim breadth, unpredictability in the art, and lack of guidance in the specification as discussed above, the instant invention is not enabled throughout the full scope of the claims.
Response to Applicant’s Arguments:
The Applicant’s arguments in the response submitted May 29th, 2026 have been carefully considered but were not found persuasive with regard to rejection of claims 1-10 under 35 USC § 112(a).
As stated in the Office action mailed 12/29/2025, while the instant Specification is enabling for bioluminescent transgenic moss gametophytes, the instant Specification does not reasonably provide enablement for the broadly claimed genus of all possible transgenic plants. The Applicant contends that the Specification teaches how to make the transgenic plants in several places, yet provides only examples in the Specification for the transformation of moss protoplasts that are transformed and bioluminesce with the exogenous addition of 3-hydroxyhispidin [see, Applicant Arguments/Remarks Made in an Amendment filed 05/29/2026; pg. 8, ¶3]. Applicant contends that this directly enables the substrate-fed transgenic plant composition comprising the recombinant fungal luciferase and intracellular fungal luciferin.
MPEP § 2164.01(a) states that “the specification may require a reasonable amount of experimentation to make and use the invention and what is reasonable will depend on the nature of the invention and the underlying art.” Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 596, 2023 USPQ2d 602 (2023). As recited in the Office action filed 12/29/2025, knowledge gained from studying mosses is only partially translatable to vascular plants [pg. 9, ¶2]. Significant differences in their fundamental biology mean that not all findings apply universally (Turetsky et al., 2012). Protoplast regeneration alone is often times not reproducible across species and the effectivity of creating bioluminescent plants would be unpredictable [Id. pg. 9, ¶3]. The Applicant does not acknowledge the challenges associated with using methodology developed for moss protoplasts for the broad scope of any material of any transgenic plant. Thus, there would be an unreasonable amount of experimentation to make and use the invention based on the nature of the invention and the underlying art.
As detailed above in the written description rejection, the recitation that autonomous bioluminescence may occur if 3-hydroxyhispidin biosynthesis occurs in host cells is not sufficiently supported in the art and the working examples provide no evidence that one of ordinary skill in the art could make or use the invention as claimed.
Applicant does not address that the instant Specification does not support any other listed luciferin compound other than 3-hydoxyhispidin, which was identified as the luciferin that most, if not all, luminous fungal species utilize [Id. pg. 9, ¶3]. As pointed out in the Office action filed 12/29/2025, alternate species of fungal luciferin acting as a subject luciferase in transgenic plants would require significant experimentation for protocol creation [Id. pg. 9, ¶3].
The Specification does not describe obtaining transgenic plants to the full scope of all possible claimed plant species/genera/families/orders/classes or the use of any other fungal luciferin with the large scope of transgenic plants claimed. Further, the Applicant’s arguments concede that the only species for which a working example was provided is the transformation of moss protoplasts and the Applicant does not address that the only fungal luciferin utilized with the moss protoplasts was 3-hydroxyhispidin. Thus, the Specification still does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims. The rejection under 35 USC § 112(a) scope of enablement is maintained.
Summary
Claims 1-10 are rejected.
A luciferase having an amino acid sequence at least 90% identical to SEQ ID NO. 2 appears to be free of prior art. The prior art fails to suggest such specifically claimed products, hence, said products are also non-obvious. Thus, claims 1-10 are deemed free of the prior art with SEQ ID NO. 2 as the elected species.
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR § 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY K. JOHNSON whose telephone number is (571)272-5761. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bratislav Stankovic can be reached at 571-270-0305. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EMILY K JOHNSON/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
Prosecution Insights