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, and 16 are canceled.
Claims 7-8, 10-15, and 17-19 are pending.
Claims 7-8, 10-15, and 17-19 are examined herein.
The rejections to claims 9 and 16 under 35 USC 112(b) have been withdrawn in view of Applicant’s cancellation of claims 9 and 16.
Claims 7-8, 10-15, and 17-19 are rejected.
Priority
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, 10, and 12 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) and Faudoa (US-20070128685-A1).
This is a modified rejection from the previous Office Action dated 07/24/2025. Claims 9 and 16 are no longer rejected under 35 USC 103 as being unpatentable over Faudoa because the claims have been canceled.
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.
Claim 10 is drawn to the method according to claim 7, 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, (v) 4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-one and any combination thereof.
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.
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 (remaining limitation of claim 7).
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, (v) 4-(3-cyclopentyloxy-4-methoxyphenyl)pyrrolidin-2-one and any combination thereof (claim 10).
wherein the PDE inhibitor concentration is from 0.10 to 100 µM (claim 12).
In analogous art Faudoa teaches an invention related to methods and compositions for cell culture (title).
Regarding the remaining limitation of claim 7, 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).
Regarding claim 10, Faudoa teaches the compound is rolipram (i.e. rolipram is also named 4-(3-cyclopentyloxy-4-methoxyphenyl) pyrrolidine-2-one or PDE4) (¶0071).
Regarding claim 12, Faudoa teaches the medium comprises a cAMP elevating agent (i.e. rolipram) 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).
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 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 to elevate cAMP levels, and incorporation of the cAMP elevating agent into the plant cell culture of Mangat 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 taught by Faudoa to increase cAMP levels in plant cell cultures for the purpose of increasing plant callus growth.
Claims 8, 11, 13, 15, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Mangat and Faudoa as applied to claim 7, and further in view of Negrutiu (Negrutiu, I., Beeftink, F., & Jacobs, M. (1975). Arabidopsis thaliana as a model system in somatic cell genetics I. Cell and tissue culture. Plant Science Letters, 5(5), 293-304).
This is a modified rejection from the previous Office Action dated 07/24/2025.
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 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 claims 8, 11, 13, 15, 18, and 19, Mangat and Faudoa teach the limitations of claim 7 as set forth in the previous obviousness rejection. The teachings of Mangat and Faudoa as they are applied to claim 7 are set forth previously herein and are incorporated by reference. Additionally regarding claim 13, Faudoa teaches the medium comprises a cAMP elevating agent (i.e. rolipram) 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).
However, Mangat and Faudoa do not explicitly teach the limitations of claims 8, 11, 13, 15, 18, and 19 as they are recited above.
Negrutiu teaches analogous art related plant cell tissue culture (title, abstract).
Regarding claim 8, Negrutiu teaches callus induction and growth from seeds, stems, and pieces of leaf (i.e. somatic embryogenesis) (abstract summary).
Regarding claims 11 and 13, Negrutiu teaches actively growing calluses were obtained on agar and in liquid cultures (i.e. the isolated plant material is cultured in a solid or in a liquid medium) (abstract summary).
Regarding claims 15, 18, and 19, Negrutiu teaches the plant material is from Arabidopsis thaliana (i.e. an herbaceous plant belonging to Arabidopsis spp. That is Arabidopsis thaliana) (abstract).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Mangat and Faudoa to include the limitations of Negrutiu to arrive at the instantly claimed method with a reasonable expectation of success because Mangat teaches cAMP promotes callus growth (abstract, Table 3), Faudoa teaches utilizing compounds including rolipram in cell culture to increase the half-life of cAMP (¶0071) and further teaches cell types that may be cultured include plant cells in meristem or callus culture (¶0154-0155), and Negrutiu teaches specific tissue culture methods for inducing callus from Arabidopsis thaliana somatic tissues in both liquid and solid medias. One having ordinary skill in the art could incorporate rolipram and the specified concentrations taught by Faudoa into the media and methods taught by Negrutiu without encountering any special technical obstacles. One having ordinary skill in the art would have been motivated to combine the teachings because Mangat teaches cAMP promotes callus growth (abstract, Table 3), Faudoa teaches utilizing compounds including rolipram in cell culture to increase the half-life of cAMP (¶0071) and further teaches cell types that may be cultured include plant cells in meristem or callus culture (¶0154-0155), and Negrutiu teaches Arabidopsis is a model system in somatic cell genetics (title) and callus may successfully be cultured on both solid and liquid media from various tissue types (abstract summary).
Claims 14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Mangat and Faudoa 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 07/24/2025.
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 and Faudoa teach the limitations of claim 7 as set forth in the previous obviousness rejection. The teachings of Mangat and Faudoa as they are applied to claim 7 are set forth previously herein and are incorporated by reference.
However, Mangat and Faudoa 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 and Faudoa 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 Faudoa, 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 Faudoa 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. 6 of remarks dated 10/21/2025 the
following arguments:
A. Independent Claim 7
Faudoa fails to disclose every requirement of claim 7. Specifically, claim 1 recites, in part: 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." (Emphasis added).
The Applicant respectfully submits that a person skilled in the art, given the technical field of the present invention (agrobiotechnology), and given the claimed method, which is directed to plants (a method of promoting in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation), would not start from a document such as Faudoa to evaluate the obviousness of the claimed method. Additionally, "in order for a reference to be proper for use in an obviousness rejection under 35 U.S.C. 103 , the reference must be analogous art to the claimed invention. In re Bigio, 381 F.3d 1320, 1325, 72 USPQ2d 1209, 1212 (Fed. Cir. 2004). A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention)." MPEP 2141.01(a). The Applicant respectfully submits that Faudoa is neither 1) in the same field of the endeavor nor is 2) reasonably pertinent to the problem faced by the inventor for at least the following reasons.
The Applicant respectfully submits that Faudoa is a document directed to compositions and methods for cell culture utilizing collagenase (collagenases are enzymes widely known in the state of the art for their use in breaking down the native collagen that holds animal tissues together), and optionally a cAMP-elevating agent. Although plant cells are mentioned in a generic list of cell types that may be cultured (for example, meristem or callus culture (see paras. [0154] , [0155])), it is respectfully submitted that the teachings of Faudoa clearly focus on mammalian cells cultures. In fact, examples provided in Faudoa are carried out with mammalian cells, for instance:
- Example 1 describes isolation and culture of human keratinocytes and fibroblasts.
- In Example 5, primary human keratinocytes were cultivated in the media from supplier A (Defined Keratinocyte Media) and in media from Supplier B (Undefined Keratinocyte- Media), with and without collagenase and forskolin.
- In Example 6, FIG. 2 presents a graph illustrating keratinocyte survival in depleted media, either supplemented or not supplemented with collagenase.
- In Example 7, Fig. 3 presents a graph illustrating population doublings of keratinocytes grown in defined media with and without collagenase and forskolin.
- In Example 8, FIG. 4 presents a graph illustrating the growth of chondrocytes in media supplemented with collagenase.
- In Example 9, FIG. 5 presents a graph illustrating fibroblast proliferation in media, either supplemented or not supplemented with collagenase
Additionally, it is respectfully stated that person skilled in the art faced with the technical problem of promoting in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation would not be prompted to apply the compositions disclosed in Faudoa.
Rather, Faudoa mentions that an exemplary application of the compositions/methods disclosed is the culture of meristem or callus culture. The mere cultivation of plant cells (e.g. meristem or callus culture) is very different from having a reasonable expectation of success in promoting reprogramming towards plant embryogenesis or microcallus formation. In other words, the promotion of plant cell reprogramming towards plant embryogenesis or microcallus formation achieved by PDE inhibitor/s (claimed method) is a technical effect that goes far beyond the mere cultivation of plant cells. Thus, Faudoa is not in the same field of endeavor as the disclosure.
Faudoa is also not reasonably pertinent either because it would not logically have commended itself to an inventor's attention in considering his problem." MPEP 2141.01(a)(I). Rather, claim 7 is directed to a completely different purpose/problem (promoting in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation) whereas Faudoa is clearly focused on mammalian cells cultures. It is respectfully submitted that cell reprogramming in plants is very different from cell reprogramming in mammalian cells. Thus, Faudoa, for these reasons and the reasons stated above, is not reasonably pertinent to the problem faced by the inventors.
Even if such a document were considered, a person skilled in the art would not be motivated to use a PDE inhibitor to promote in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation.
In para. [0083] of Faudoa, it is described that one major problem in cell culture is proliferation and contamination by fibroblast. Among the effects described for the compositions and methods disclosed in Faudoa (para. [0083]) are the following: reduction of fibroblast proliferation and contamination and enhancing the fibroblast proliferation (effects associated with mammalian cell cultures, not with plants). It is also mentioned that cell culture may be enhanced by, e.g., increasing the purity of the culture, increasing the time to senescence, increasing the population doublings possible in culture, and the like.
However, as mentioned above, claim 7 is directed to a completely different purpose/problem (promoting in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation). A person skilled in the art, in view of Faudoa, would not have expectation of success in promoting in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation.
Furthermore, cell reprogramming is not mentioned anywhere in Faudoa. Even if there were any suggestion that compositions/methods disclosed in Faudoa could promote cell reprogramming, cell reprogramming in plants is very different from cell reprogramming in mammalian cells (see Olariu V, Nilsson J, Jonsson H, Peterson C. Different reprogramming propensities in plants and mammals: Are small variations in the core network wirings responsible? PLoS One. 2017 Apr 6;12(4):e0175251. doi: 10.1371/journal.pone.0175251) such as those tested in the results presented in Faudoa.
Therefore, even if it were suggested that these compositions or methods disclosed in Faudoa could have an impact on mammalian cell reprogramming, it would be highly questionable to apply said compositions or methods to plants with reasonable expectations of success in achieving such reprogramming, much less towards plant embryogenesis or microcallus formation.
In sum, it is respectfully considered that Faudoa is neither 1) in the same field of the endeavor nor 2) reasonably pertinent to the problem faced by the inventor. Additionally, an expert in the field, in view of Faudoa, would not arrive to the method defined in claim 7, and therefore Faudoa is not a proper reference for use in an obviousness rejection under 35 U.S.C. 103, for at least these reasons.
As Faudoa is not a proper reference, and fails to disclose every requirement of claim 7, claim 7 is allowable over Faudoa.
Applicant argues depending claims depend directly or indirectly from claim 7 which Applicant has argued is allowable, and therefore depending claims should also be allowable for at least the same reasons.
This argument has been fully considered and is found not persuasive for
the following reason(s):
In view of Applicant’s arguments, a modified rejection has been made to claims 7, 10, and 12 in view of Mangat and Faudoa. Mangat teaches cyclic AMP promotes callus growth of plant cells (abstract, Table 3). 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). Although Faudoa emphasizes mammalian cell culture, Faudoa also teaches the invention may be applied to plant cells in meristem or callus culture (¶0154-0155). Based on these teachings in the prior art, Faudoa is relevant and analogous art and it would be obvious to combine the teachings of Mangat and Faudoa to increase cAMP levels in plant cell culture for the purpose of promoting callus growth (i.e. microcallus formation) (see full 103 rejection above).
Regarding Applicant’s argument that “Even if such a document were considered, a person skilled in the art would not be motivated to use a PDE inhibitor to promote in vitro plant cell reprogramming towards plant embryogenesis or microcallus formation.”, a modified 103 rejection has been made in view of Mangat and Faudoa. As stated above and in the modified 103 rejection set forth previously herein, it would be obvious to combine the teachings of Mangat and Faudoa to increase cAMP levels in plant cell culture for the purpose of promoting plant callus growth (i.e. microcallus formation) (see full 103 rejection above).
For the reasons above, Applicant’s arguments are not found persuasive and modified rejections under 35 USC 103 to the independent and dependent claims have been made.
Conclusion
No claims are allowed.
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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