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 .
Claim Status
Claims 1-12 and 14 are pending. Claims 13 and 15-18 have been cancelled.
Election/Restrictions
Applicant’s election without traverse of the species of Pik-1 in the reply filed on 13 May 2026 is acknowledged.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., see at least p. 3). Applicant is required to delete all embedded hyperlinks and/or other forms 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.
The listing of references in the specification beginning on page 33 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.
The specification is objected to for having multiple typographical errors. For example, the specification discloses “Wes elected” on page 19 and line 23. It is suggested that Applicant review the specification for additional typographical errors.
Appropriate action is advised.
Claim Objections
Claim 3 is objected to for reciting the limitation “NLR” without first claiming the definition of the abbreviation.
Claim 4 presents the same issue for reciting “CC-NB-LRR”.
Appropriate action is advised.
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 6 and 7 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.
Claim 6 recites the limitation “the modified” NLR protein: there is insufficient antecedent basis for this limitation as the claim, or claims from which claim 6 depends, is not directed to a “modified” protein.
Claim 7 is rejected for depending upon a rejected base claim and for failing to remedy the issues of indefiniteness.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-12 and 14 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 making a chimeric construct comprising NLR Pikm-1 having the integrated HMA domain substituted with camelid nanobody targeting GFP, does not reasonably provide enablement for making and/or using the chimeric proteins as broadly claimed. 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/use the invention commensurate in scope with these claims.
In In re Wands (8 USPQ2d 1400 (CAFC 1988)), the CAFC considered the issue of enablement in molecular biology. The CAFC summarized eight factors to be considered in a determination of "undue experimentation". These factors include: (a) the quantity of experimentation; (b) the amount of guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the predictability of the prior art; (g) the breadth of the claims; and (h) the relative skill in the art. The factors are analyzed in turn for the instant case as follows:
The claims are drawn broadly to a chimeric protein comprising a binding molecule having any possible structure operably linked to any possible plant immune receptor protein and that may be an NLR protein having the general structure CC-NB-LRR, wherein the binding molecule broadly encompasses any possible nanobody, and wherein the NLR protein corresponds to Pik-1, a nucleic acid molecule comprising said chimeric protein and a plant cell comprising said chimeric protein.
Meanwhile, the specification teaches “Pikobodies” confer resistance against engineered potato virus X strains expressing fluorescent proteins in tobaco and can be stacked (see Fig. 2, 3 and 11 descriptions). The specification teaches that the “ploop” motif is required for Pikobody mediated HR tobacco (Fig. 14 description).
However, the specification fails to teach or provide the requisite guidance for making and/or using the genus of binding molecules, nanobodies, plant immune receptor proteins and NLRs as broadly claimed.
Here, these limitations encompass a vast number of structures yet the specification has only provided the working examples of using “PikobodyEnhancer” or “PikobodyLaM4”. Moreover, and even assuming one could use these chimeric proteins, the specification fails to specifically teach how to, in fact, make “PikobodyEnhancer” or “PikobodyLaM4”.
Appropriate guidance for making binding molecules, nanobodies, plant immune receptor proteins and NLRs as claimed is critical because each is defined and claimed by function rather than structure. For example, the specification teaches that a plant immune receptor is preferably an NLR protein meaning that the claims encompass any conceivable plant immune receptor (p. 4, last ¶).
Even NLRs encompass a vast genus of structures: plant NLR proteins usually contain a C-terminal LRR domain and a central NB-ARC domain and generally fall into two groups depending on their N-terminal structures and that they typically will be of the structure CC-NB-LRR domain where this sequence of an NLR may have as little as 60% sequence identity to said protein or domain meaning that NLRs need not comprise any of these structures (p. 4, last ¶ bridging p. 5).
The limitation nanobody presents the same issue: the specification teaches that a nanobody is specific for an effector protein from a plant pathogen, and the chimeric protein is capable of activating immune signaling in a plant cell upon binding of the effector protein to the nanobody or may be specific for other ligands (p. 2). Thus, the specification teaches a nanobody by way of function.
However, the specification fails to teach the structures of any nanobody other than a camelid nanobody. This teaching is critical in light of the state of the art which provides that nanobodies are usually derived from camelids such as llamas (Fridy et al, 2014, Nat Methods, 11(12):1253-1260; see p. 2, ¶ 2; see also De Coninck et al, 2017, Frontiers in Microbiology, 8:1-10).
Thus, without teaching nanobodies other than those that are derived from camelid, the skilled practitioner would be unable to predictable make and/or use the genus of nanobodies as broadly encompassed by the claims.
Moreover, the specification has failed to teach, in fact, that the genus of chimeric proteins as broadly claimed may be predictably used. This is critical because the art teaches that not all NLR-nanobody chimeric proteins retain functional activity: out of 11 tested chimeric proteins almost half exhibit autoimmunity and that only 36% of chimeric proteins produced a hypersensitive response (Kourelis et al, 2023, Science, 379:934-939; see p. 1, col. 2, last ¶ bridging col. 3).
Therefore, in light of the breadth of the claims, the failure of the specification to teach binding molecules, nanobodies, plant immune receptor proteins and NLRs as broadly claimed, the lack of working examples and the state of the art which teaches NRLs lack functional activity, the skilled artisan would resort to impermissible undue trial and error experimentation to arrive at the chimeric proteins as broadly claimed.
Claims 1-12 and 14 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.
Claims 1-12 and 14 are drawn broadly to a chimeric protein comprising a binding molecule having any possible structure operably linked to any possible plant immune receptor protein of any possible structure and that may be an NLR protein having the general structure CC-NB-LRR, wherein the binding molecule broadly encompasses any possible nanobody, and wherein the NLR protein corresponds to Pik-1, a nucleic acid molecule comprising said chimeric protein and a plant cell comprising said chimeric protein.
Meanwhile, the specification describes “Pikobodies” confer resistance against engineered potato virus X strains expressing fluorescent proteins in tobaco and can be stacked (see Fig. 2, 3 and 11 descriptions). The specification describes that the “ploop” motif is required for Pikobody mediated HR tobacco (Fig. 14 description).
The written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
However, the specification fails to describe a representative number of structures as claimed, and further fails to describe a representative number of structures from the broad genus of binding molecules, nanobodies, plant immune receptor proteins and NLRs that retain functional activity to activate immune signaling upon binding of the effector protein to the nanobody.
Here, these limitations encompass a vast number of structures yet the specification has only described expressing “PikobodyEnhancer” or “PikobodyLaM4”. However, the specification has, in fact, failed to describe the structures of “PikobodyEnhancer” or “PikobodyLaM4”.
A description of the binding molecules, nanobodies, plant immune receptor proteins and NLRs as claimed is critical because each is defined and claimed by function rather than structure. For example, the specification describes that a plant immune receptor is preferably an NLR protein meaning that the claims encompass any conceivable plant immune receptor (p. 4, last ¶).
Even NLRs encompass a vast genus of structures: plant NLR proteins usually contain a C-terminal LRR domain and a central NB-ARC domain and generally fall into two groups depending on their N-terminal structures and that they typically will be of the structure CC-NB-LRR domain where this sequence of an NLR may have as little as 60% sequence identity to said protein or domain meaning that NLRs need not comprise any of these structures (p. 4, last ¶ bridging p. 5).
The limitation nanobody presents the same issue: the specification describes that a nanobody is specific for an effector protein from a plant pathogen, and the chimeric protein is capable of activating immune signaling in a plant cell upon binding of the effector protein to the nanobody or may be specific for other ligands (p. 2). Thus, the specification describes a nanobody by way of function.
However, the specification fails to arguably describe the structures of any nanobody other than a camelid nanobody. This description is critical in light of the state of the art which provides that nanobodies are usually derived from camelids such as llamas (Fridy et al, see p. 2, ¶ 2; see also De Coninck et al).
Thus, without describing nanobodies other than those that are derived from camelid, the skilled practitioner would not be of the opinion that Applicant possesses the genus of nanobodies as broadly encompassed by the claims.
Moreover, the specification has failed to describe, in fact, that the genus of chimeric proteins as broadly claimed may be predictably used. This is critical because the art describes that not all NLR-nanobody chimeric proteins retain functional activity: out of 11 tested chimeric proteins almost half exhibit autoimmunity and that only 36% of chimeric proteins produced a hypersensitive response (Kourelis et al, see p. 1, col. 2, last ¶ bridging col. 3).
Therefore, in light of the breadth of the claims, the failure of the specification to describe a representative number binding molecules, nanobodies, plant immune receptor proteins and NLRs as broadly claimed or a structure-function thereof, the lack of working examples and the state of the art which describes that NRLs lack functional activity, the skilled artisan would not be of the opinion that Applicant possessed the chimeric proteins as broadly claimed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3, 4, 8, 12 and 14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cesari et al (2021, bioRxiv, https://doi.org/10.1101/2021.04.24.441256, p. 1-34).
Instant claims 1, 3, 4, 8, 12 and 14 are drawn broadly to a chimeric protein comprising a binding molecule operably linked to a plant immune receptor protein that Is an NLR protein having the general structure CC-NB-LRR and wherein the NLR protein corresponds to RGA5 (i.e., a receptor-like protein), a nucleic acid molecule comprising said chimeric protein and a plant cell comprising said chimeric protein.
Cesari et al disclose a chimeric protein comprising a NLR protein that is RGA5 wherein the integrated domain is replaced with the binding molecule of Pikp-1 HMA domain residues which is introduced into tobacco and activates immune signaling (see Summary; see also Fig. 7). Cesari et al disclose that these are chimeric proteins in so far as they are tagged proteins (p. 14, lines 451-461).
Cesari et al disclose that NRL receptors are key elements of plant immunity and confer resistance to many crop diseases making NRL proteins widely used in crop breeding programs (p. 3, lines 44-65).
Therefore, a chimeric protein comprising a binding molecule operably linked to a plant immune receptor protein that Is an NLR protein having the general structure CC-NB-LRR and wherein the NLR protein corresponds to RGA5 (i.e., a receptor-like protein), a nucleic acid molecule comprising said chimeric protein and a plant cell comprising said chimeric protein is anticipated by Cesari et al.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JASON DEVEAU-ROSEN whose telephone number is (571)272-2828. The examiner can normally be reached 7:30am - 4pm.
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/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
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