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 .
Status of the Claims
Claims 1-6, 9-10, and 16 are cancelled.
Claims 7-8, 11-15, and 17-19 are pending.
Claims 7-8, 11-15, and 17-19 are examined herein.
Claims 7-8, 11-15, and 17-19 are rejected.
Priority
As previously stated, Application No. 18/720,938 filed on 06/17/2024 is a 371 of PCT Application No. PCT/EP2022/085208 filed on 12/09/2022, and also claims foreign priority to European Patent Application No. EP21383157.1 filed on 12/17/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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.
Claims 7-8, 11-13, 15, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Mangat (Mangat, B. S., & Janjua, S. (1987). Cyclic Nucleotides and In Vitro Plant Cultures: I. INDUCTION OF ORGANOGENESIS IN TOBACCO (NICOTIANA TABACUM CALLUS CULTURES. Journal of experimental botany, 38(12), 2059-2067), Faudoa (US-20070128685-A1), Smith (Boswell‐Smith, V., Spina, D., & Page, C. P. (2006). Phosphodiesterase inhibitors. British journal of pharmacology, 147(S1), S252-S257.), and Wu (Wu, Y., Haberland, G., Zhou, C., & Koop, H. U. (1992). Somatic embryogenesis, formation of morphogenetic callus and normal development in zygotic embryos of Arabidopsis thaliana in vitro. Protoplasma, 169(3), 89-96.).
This is a modified rejection from the previous Office Action dated 12/29/2025, necessitated by Applicant’s amendments.
Claim 7 is drawn to a method of promoting in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation, comprising:a) Culturing an isolated plant material with at least one phosphodiesterase (PDE) inhibitor,wherein the PDE inhibitor is selected from the list consisting of:(i) 3-(2,6-Difluorophenyl)-2-methylthio-4-oxo-3,4-dihydroquinazoline, (ii)(R)-N-(3-chlorobenzyl)-1-((2-(2-fluorophenyl)-5-methyloxazol-4-yl)methyl)piperidin- 3-carboxamide, (iii) 2-(2-Bromophenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole, (iv)3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4- (difluoromethoxy)benzamide, and any combination thereof; and wherein the isolated plant material is an isolated microspore, and isolated protoplast, or an immature zygotic embryo.
Claim 8 is drawn to the method according to claim 7, wherein the plant embryogenesis is microspore embryogenesis or somatic embryogenesis.
Claim 11 is drawn to the method according to claim 7, wherein the isolated plant material is cultured in a solid medium or in a liquid medium.
Claim 12 is drawn to the method according to any one of claim 7, wherein the PDE inhibitor concentration is from 0.10 to 100 µM.
Claim 13 is drawn to the method according to claim 12, wherein the PDE inhibitor concentration is from 0.10 to 19 µM when the isolated plant material is cultured in a liquid medium.
Claim 15 is drawn to The method according to claim 7, wherein the plant material belongs to a crop plant, forest plant, or an herbaceous plant.
Claim 18 is drawn to the method according to claim 15, wherein the plant material belongs to Brassica spp., Quercus spp. or Arabidopsis spp.
Claim 19 is drawn to the method according to claim 15, wherein the plant material belongs to Brassica napus sp., Quercus suber sp. or Arabidopsis thaliana sp.
Regarding claim 7, Mangat teaches cyclic AMP (cAMP) promotes callus growth of plant cell cultures (abstract, results ¶3, Table 3) (i.e. reasonably interpreted as promoting in vitro plant cell reprogramming towards plant microcallus formation according to Applicant’s definition of microcallus formation on p. 9, lines 26-27 of specification).
However, Mangat does not explicitly teach:
Culturing an isolated plant material with at least one phosphodiesterase (PDE) inhibitor, and wherein the PDE inhibitor is selected from the list consisting of:
(i) 3-(2,6-Difluorophenyl)-2-methylthio-4-oxo-3 ,4- dihydroquinazoline,
(ii) (R)-N-(3-chlorobenzyl)-1 -((2-(2-fluorophenyl)-5-methyloxazol-4- yl)methyl)piperidin-3- carboxamide,
(iii) 2-(2-Bromophenyl)-4,5-bis(4-methoxy phenyl)- 1H-imidazole, (iv) 3-(cyclopropylmethoxy )-N-(3,5-dichloropyridin-4-yl)-4- (difluoromethoxy)benzamide, and any combination thereof
and wherein the isolated plant material is an isolated microspore, and isolated protoplast, or an immature zygotic embryo (remaining limitations of claim 7)
The limitations of claims 8, 11-13, 15, and 18-19 as recited above.
Regarding the remaining limitation of claim 7, In analogous art, Faudoa teaches an invention related to methods and compositions for cell culture (title). Faudoa teaches use of a cell culture medium containing cAMP-elevating agents which include agents that increase intracellular cAMP levels through inhibition of a cAMP phosphodiesterase (¶0006, 0069), and further teaches compounds which may inhibit cAMP phosphodiesterase(s) include rolipram (¶0071). In an alternative embodiment, Faudoa teaches cell types that may be cultured include plant cells in meristem or callus culture (¶0154-0155). In other art regarding cAMP-specific PDE inhibitors, Smith teaches both Rolipram and Roflumilast are known, cAMP-specific PDE4 inhibitors that elevate intracellular levels of cAMP (p. S253-S254, and Table 1). In other analogous art, Wu teaches the induction of callus from a model species, Arabidopsis, for plant regeneration is derived from protoplasts (p. 90, ¶1) and also may be derived from early/immature zygotic embryos (abstract, p. 91 section titled Proportion of surviving and developing embryos, p. 92-93 section titled Callus formation and shoot regeneration, p. 95, last sentence of ¶1).
Regarding claim 8, Wu teaches the induction of Arabidopsis callus may be derived from early/immature zygotic embryos (i.e. wherein the plant embryogenesis is somatic embryogenesis) (abstract, p. 91 section titled Proportion of surviving and developing embryos, p. 92-93 section titled Callus formation and shoot regeneration, p. 95, last sentence of ¶1).
Regarding claim 11, Wu teaches the isolated plant material was cultured in liquid media (p. 91, section titled Materials and methods).
Regarding claim 12, Faudoa teaches the medium comprises a cAMP elevating agent (i.e. rolipram, a PDE4 inhibitor) at a concentration of 0.5-5.0 ug/mL (i.e. rolipram has a molar mass of 275.35, therefore Faudoa teaches the cAMP elevating agent has a concentration of approximately 1.8 µM to 18 µM).
Regarding claim 13, Faudoa teaches the medium comprises a cAMP elevating agent (i.e. rolipram, a PDE4 inhibitor) at a concentration of 0.5-5.0 µg/mL (i.e. rolipram has a molas mass of 275.35, therefore Faudoa teaches the cAMP elevating agent has a concentration of approximately 1.8 µM to 18 µM).
Regarding claims 15, 18, and 19, Wu teaches the plant material is from Arabidopsis thaliana (i.e. an herbaceous plant belonging to Arabidopsis spp. That is Arabidopsis thaliana) (title, abstract, entire document).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention taught by Mangat to include the limitations of Faudoa, Smith, and Wu to arrive at the instantly claimed method with a reasonable expectation of success because Mangat teaches cAMP promotes callus growth of plant cell cultures, Faudoa teaches cell cultures including plant callus may be cultured with cAMP elevating agents including rolipram (i.e. a PDE4 inhibitor) to elevate cAMP levels, Smith teaches another known and readily available cAMP-elevating PDE4 inhibitor is Roflumilast, and Wu teaches callus cultures of the model species Arabidopsis may successfully be derived from isolated protoplasts and immature zygotic embryos. Incorporation of the cAMP elevating agent Roflumilast into the plant cell culture of Mangat and/or Wu could be achieved by one of ordinary skill in the art to increase cAMP levels in plant cell cultures without encountering any special technical obstacles. One having ordinary skill in the art would have been motivated to combine the teachings because Mangat teaches cyclic AMP (cAMP) promotes callus growth of plant cell cultures (abstract, results ¶3, Table 3), therefore it would be obvious to include cAMP elevating agents such as the PDE4 inhibitor Rolipram taught by Faudoa to increase cAMP levels in plant cell cultures for the purpose of increasing plant callus growth. Furthermore, it would therefore have been obvious to a person of ordinary skill to include the PDE4 inhibitor Roflumilast taught by Smith to arrive at the instantly claimed method with a reasonable expectation of success because Roflumilast taught by Smith was a known and readily available PDE4 inhibitor. One having ordinary skill in the art would have been motivated to combine the teachings because it would have been prima facie obvious to substitute the PDE4 inhibitor (rolipram) taught by Faudoa with another PDE4 inhibitor known in the art, roflumilast, for the same purpose. It would further be obvious to utilize the same or similar concentrations of the PDE4 inhibitor Roflumilast in the cell culture as is taught by Faudoa regarding PDE4 inhibitor Rolipram to achieve the same outcome. Lastly, one of ordinary skill in the art would have been motivated to combine the teachings of Wu because callus cultures used for Arabidopsis plant regeneration are often derived from the instantly claimed isolated plant material.
Claims 14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Mangat, Faudoa, Smith, and Wu as applied to claim 7, and further in view of Saad (Saad, A. I., & Elshahed, A. M. (2012). Plant tissue culture media. Recent advances in plant in vitro culture, 25(7), 30-40).
This is a modified rejection from the previous Office Action dated 12/29/2025, necessitated by Applicant’s amendments.
Claim 14 is drawn to the method according to claim 12, wherein the PDE inhibitor concentration is from 20 to 80 µM, when the isolated plant material is cultured in a solid medium.
Claim 17 is drawn to the method according to claim 14, wherein the PDE inhibitor concentration is 50 µM.
Regarding claims 14 and 17, Mangat, Faudoa, Smith, and Wu teach the limitations of claim 7 as set forth in the previous obviousness rejection. The teachings of Mangat, Faudoa, Smith, and Wu as they are applied to claim 7 are set forth previously herein and are incorporated by reference.
However, Mangat, Faudoa, Smith, and Wu do not explicitly teach:
wherein the PDE inhibitor concentration is from 20 to 80 µM, when the isolated plant material is cultured in a solid medium (claim 14); or
wherein the PDE inhibitor concentration is 50 µM (claim 17).
In analogous art related to plant tissue culture media (title), Saad teaches optimal growth and morphogenesis of tissues may vary for different plants according to their nutritional requirements. Moreover, tissues from different parts of plants may also have different requirements for satisfactory growth (p. 29, introduction). Saad further teaches plant tissue culture media should comprise many various components, and it should be considered that the optimum concentration of each nutrient for achieving maximum growth rates varies among species (p. 29, media composition).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Mangat, Faudoa, Smith, and Wu to include the limitations of Saad to arrive at the instantly claimed method with a reasonable expectation of success because Saad teaches optimum concentration of media components varies among species and should be considered (p.29, media composition), and one of ordinary skill could test various concentrations of the PDE inhibitor taught by Wu, including the instantly claimed concentrations, without encountering any special technical obstacles. One having ordinary skill in the art would have been motivated to test various concentrations of the PDE inhibitor compound taught by Wu for the purpose of optimizing the concentration according to the species being cultured as taught by Saad (p. 29, media composition), including the concentrations of 20 to 80 µM, and 50 µM.
Response to Arguments
Applicant argues beginning on p. 7 of remarks dated 03/26/2026 the
following arguments:
A. Independent Claim 7
Mangat in view of Faudoa fails to disclose every requirement of claim 7, Specifically, claim 7 requires a PDE inhibitor selected from the group consisting of compounds (i)-(iv) and "wherein the isolated plant material is an isolated microspore, and isolated protoplast, or an immature zygotic embryo." The Applicant respectfully submits that the prior art does not disclose these limitations for at least the following reasons.
A. The prior art does not teach or suggest the claimed PDE inhibitors
Amended claim 7 now requires a PDE inhibitor selected from the group consisting of compounds (i)-(iv). The Office has asserted that Faudoa teaches the compound rolipram, also known as 4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-one which is a PDE4 (para. [0071]). However, rolipram is no longer listed in the claim. Accordingly, the cited prior art does not teach the group of PDE inhibitors found in independent claim 7.
B. The prior art does not teach or suggest the claimed isolated plant materials
In addition to above, amended claim 7 now requires that the isolated plant material is an isolated microspore, an isolated protoplast, or an immature zygotic embryo.
In contrast, Mangat teaches induction of organogenesis in tobacco (Nicotiana tabacum) callus cultures (Abstract). Callus cultures are fundamentally different from isolated microspores, isolated protoplasts, or immature zygotic embryos. Callus is an undifferentiated mass of cells that has already been established through prior culture, whereas microspores are immature male gametophytes, protoplasts are plant cells with their cell walls removed, and immature zygotic embryos are embryonic plant structures at an early developmental stage. All single cell systems have in common that a differentiation pathway is present (e.g. towards pollen development or towards mesophyll cell) and a re-programming way from this pathway towards embryogenesis has to be achieved. In contrast, callus cells represent undifferentiated cells by definition.
Faudoa teaches cell types that may be cultured include plant cells in meristem or callus culture. Faudoa does not teach or suggest the use of isolated microspores, isolated protoplasts, or immature zygotic embryos.
Negrutiu teaches callus induction and growth from seeds, stems, and pieces of leaf (Abstract), which are somatic tissues, not isolated microspores, isolated protoplasts, or immature zygotic embryos. Saad teaches general principles of plant tissue culture media composition but does not teach or suggest any specific isolated plant material.
As Mangat in view of Faudoa fails to disclose every requirement of claim 7, claim 7 is allowable over Mangat.
B. Dependent Claims 10 and 12
Claim 10 has been cancelled, rendering the rejection to this claim moot. The Applicant respectfully submits that since claim 12 depends directly on independent claim 7, claim 12 contains all requirements of independent claim 7. Therefore, since independent claim 7 should be allowed, as argued above, pending dependent claim 12 should be allowed for at least the same reasons articulated for claim 7.
C. Dependent Claims 8, 11, 13, 15, 18 and 19
The Applicant respectfully submits that since claims 8, 11, 13, 15, 18 and 19 depend directly or indirectly on independent claim 7, claims 8, 11, 13, 15, 18 and 19 contain all requirements of independent claim 7. Negrutiu fails to address the shortcomings of Mangat and Faudoa as identified supra relative to claim 7. Therefore, since independent claim 7 should be allowed, as argued above, pending dependent claims 8, 11, 13, 15, 18 and 19 should be allowed for at least the same reasons articulated for claim 7.
D. Dependent Claims 14 and 17
The Applicant respectfully submits that since claims 14 and 17 depend indirectly on independent claim 7, claims 14 and 17 contain all requirements of independent claim 7. Saad fails to address the shortcomings of Mangat and Faudoa as identified supra relative to claim 7. Therefore, since independent claim 7 should be allowed, as argued above, pending dependent claims 14 and 17 should be allowed for at least the same reasons articulated for claim 7.
This argument has been fully considered and is found not persuasive for
the following reason(s):
In view of Applicant’s amendments, a modified rejection to independent claim 7 has been made in view of Mangat, Faudoa, Smith, and Wu. Because there is explicit teaching to culture plant cells with rolipram which is a known PDE4 inhibitor because PDE4 inhibitors elevate intracellular cAMP, it would also be prima facie obvious to substitute rolipram as taught by Faudoa with another known, readily available PDE4 inhibitor (instantly claimed Roflumilast, aka 3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4- (difluoromethoxy)benzamide) for the same purpose. Additionally, Wu teaches callus for plant regeneration is often derived from protoplasts and immature zygotic embryos. Thus, it would be obvious to culture these isolated plant materials with the claimed PDE inhibitors to promote callus formation/ growth for plant regeneration. For this reason, Applicant’s argument regarding the independent claim is not found persuasive.
Applicant essentially argues the rejections to the pending depending claims should be withdrawn because they depend from independent claim 7 of which Applicant believes is allowable. Because independent claim 7 is obvious in view of Mangat, Faudoa, Smith, and Wu (see directly above), and further because the limitations of the dependent claims are also obvious, the dependent claims remain rejected under modified 35 USC 103 rejections (see previously herein).
Conclusion and Inquiries
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
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JESSICA N. STOCKDALE
Examiner
Art Unit 1663
/JESSICA NICOLE STOCKDALE/Examiner, Art Unit 1663
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
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