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 .
Election/Restrictions
The Office acknowledges Applicant’s response to the Species Election Requirement filed on July 22, 2026. Applicant elected the Penicillium species, corresponding to SEQ ID NO: 1-6, and indicated that all pending claims encompass the elected species. Because no traverse was presented the election is treated as an election without traverse.
Claim Status
Claims 1-22 are pending.
Claims 1-22 are examined on the merits.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 9 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception, namely a product of nature, without additional elements sufficient to integrate the exception into a practical application or amount to significantly more than the exception.
Claim 9 recites a medicinal compound produced from the modified plant, seed, cell, or plant part of claim 1. Under BRI, the claimed subject matter is the medicinal compound itself. The phrase “produced from the modified plant, seed, cell, or plant part” identifies how or where the compound is produced, but claim 9 does not require the resulting medicinal compound to possess any particular structural, functional, or other characteristic different from the naturally occurring counterpart.
For example, fusidic acid is a medicinal compound encompassed by claim 9 (pa00142). Godtfredsen (W. O. Godtfredsen et. al., Nature (1962) No.4819, pp987) discloses fusidic acid as a naturally occurring compound produced by Fusidium coccineum. Thus, fusidic acid is a product or nature having a naturally occurring counterpart. Claim 9 does not require the plant-produced fusidic acid to possess any structural, chemical, functional, or other characteristic that is markedly different from naturally occurring fusidic acid. Accordingly, claim 9 encompasses a product of nature that does not have markedly different characteristics from its naturally occurring counterpart.
The limitation that the compound is “produced from” the modified plant, seed, cell, or plant part merely identifies its source or manner of production and does not distinguish compound itself from the naturally occurring compound. Therefore, the claimed medicinal compound is directed to a product-of nature judicial exception.
Accordingly, claim 9 encompasses a naturally occurring product without markedly different characteristics and is not patent-eligible under § 101.
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 15, 16, and 19 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 15 recites “The method of claim 13, the method further comprising regenerating at least one modified plant or plant part from the at least one selected plant cell or a descendant thereof”. However, claim 15 depends from claim 13, and claim 13 does not previously introduce or define “the at least one selected plant cell”. Although claim 14 recites selecting at least one plant cell comprising the heterologous polypeptide molecule, claim 15 does not depend from claim 14. Therefore, it is unclear what previously recited selected plant cells provides antecedent basis for “the at least one selected plant cell” in claim 15.
Claim Rejections - 35 USC § 112
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.
Scope of Enablement
Claims 1-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specifications, while being enabling for editing the expression of the specifically disclosed penicillin biosynthetic proteins encoded by the nucleotide sequences corresponding to ACVS, IPNS, IAT, PaaT, PenV, and PenM (and the corresponding amino acid sequences); does not reasonably provide enablement for the full scope of the claimed invention, namely the broader genera of proteins having at least about 85% amino acid senesce identity to the disclosed proteins while retaining the respective catalytic or transport functions required for penicillin biosynthesis. 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 and/or use the invention commensurate in scope with these claims.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(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. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
Under the broadest reasonable interpretation consistent with the specification, the claims 1, 2, 7, 16, and 19 encompass modified plants, plant cells, seeds, or plant parts comprising nucleotide sequences encoding penicillin biosynthetic proteins having at least about 85% amino acid sequence identity to the disclosed proteins, including ACVS, IPNS, IAT, PaaT, PenV, and PenM, while retaining the respective functions necessary for penicillin production. Thus, the claims are not limited to the specifically disclosed amino acid sequences, but encompass broad general of protein variants that may differ from each disclosed protein at up to approximately 15% of the amino acid positions.
For purpose of this rejection, plant transformation, heterologous gene expression, and assembly of biosynthetic pathways in plants were generally within the level of ordinary skill in the art. The enablement deficiency is therefore not based on an inability to introduce or express the claimed sequences in a plant. Rather, the deficiency concerns whether the specification enables a person of ordinary skill in the art to identify, without undue experimentation which proteins throughout the claimed 85% sequence-identity genera retain the catalytic or transport functions required for penicillin biosynthesis.
The specification discloses one representative amino acid sequence for each of the six-penicillin biosynthetic proteins and generally states that variants may contain substitutions, insertions, or deletions. However, the specification does not identify the amino acid residues necessary to preserve the catalytic, substrate-recognition, transport, folding, stability, or interdomain functions of the claimed proteins. The specification also does not disclose a representative number of functional variants spanning the claimed genera or provide sufficient structure-function guidance for predicting which proteins having at least about 85% sequence identity will retain the required activity.
ACVS is illustrative of this enablement deficiency. The specification identifies ACVS as a large multidomain nonribosomal peptide synthetase comprising adenylation, thiolation, condensation, epimerization, and thioesterase domains. The specification further explains that ACVS selects activates, and condenses L-α-aminoadipic acid, L-cysteine, and L-valine to produce the ACV intermediate required for penicillin biosynthesis. Proper ACVS function therefore depends on the coordinated operation of multiple catalytic domains, substrate-recognition regions, carrier-protein regions, and interdomain interactions.
The specification reports that the disclosed ACVS coding sequence is approximately 11.331 kilobases, corresponding to a protein of approximately 3,700 amino acids. An ACVS protein having 85% identity to the disclosed sequence may therefore differ at approximately 555 amino acid positions. Consistent with this conclusion, structure-function studies of nonribosomal peptide synthetase adenylation domains establish that substrate recognition depends on a limited number of residues forming the substrate-binding pocket and catalytic architecture. Alternation of such residues may change substrate specificity or catalytic activity without substantially reducing overall sequence identity according to Stachelhaus (Torsten Stachelhaus et. al., Chemistry & Biology (1999) Vol6 No 8, pp493-505) (p503, left column, pa1). Likewise, proper movement add interaction of carrier and catalytic domains are necessary for the sequential transfer and condensation reactions performed by multidomain nonribosomal peptide synthetase, thus, overall percentage identify alone does not identify whether a particular ACVS variant preserved the substrate recognition, catalytic activity, conformational movement, and interdomain coordination required to synthesize ACV Challis (Gregory L Challis et. al., Chemistry & Biology (2000) Vol 7 No 3, pp211-224) (p211, “Background”, “Results” and “conclusion”; “Functional analysis of amino-acid-activating domains”; “Substrates with hydrophobic sidechains”; “Substrates with polar sidechains”). The claimed identity threshold does not restrict where those differences may occur. Such changes may occur within substrate-binding regions, catalytic motifs, carrier-protein regions, domain interfaces, linker regions, or structural elements required for proper folding and activity.
Changes at functional significant positions may alter substrate recognition, prevent substrate activation, disrupt transfer of pathway intermediates, impair stereochemical control, destabilize the protein, interfere with coordinated domain activity, or eliminate ACVS activity. Accordingly, overall amino acid sequence identity of 85% does not by itself, establish that a particular ACVS variant will retain the multiple coordinated functions required to produce the ACV intermediate.
The specification does not identify which ACVS amino acid positions are essential, which positions tolerate substitution, which domains must remain conserved, or which combinations of substitutions preserve ACVS activity. Nor does the specification disclose representative functional ACVS variants distributed throughout the claimed 85% sequence-identity genus. General statements that substitutions, including conservative substitutions, may be made do not provide sufficient guidance for selecting functional members throughout a genus that permits hundreds of amino acid differences in a multidomain enzyme.
The claims encompass extensive genera of variants for six functionally distinct proteins. Each protein may differ from the corresponding disclosed sequence by as much as approximately 15%, provided that the resulting protein ultimately performs the required function in the penicillin biosynthetic pathway. The claims do not limit the substitutions to nonessential residues, conserved substitutions, particular domains, or variants shown to possess a defined level of activity.
The predictability of the relationship between overall sequence identity and retained function is limited. A protein may satisfy the numerical identity threshold while containing changes at residues important for substrate binding, catalysis, protein folding, stability, domain interaction, or transport. Conversely, substitutions at some positions may be tolerated. The specification does not provide sufficient information for reliably distinguishing these categories based merely on the overall percentage of sequence identity.
The amount of guidance and the number of working examples are insufficient relative to the breadth of the claimed genera. The specification provides the specifically disclosed sequences and general descriptions of possible sequence variation, but is does not provide activity data for representative 85% identity variants, identify permissible and impermissible substitutions, define conserved functional region’s that must remain unchanged, or produce predictive rules correlating sequence change with retained catalytic or transport function.
Consequently, a person of ordinary skill in the art would be required to generate and test numerous protein variants to determine which members of the claimed genera remain operative. For ACVS, such testing would require determining whether each variant is properly expressed and folded, whether the individual catalytic domains remain active, whether the required substrate are correctly recognized and activated, whether intermediates are transferred between domains, and whether ACV is produced. Similar testing would be necessary to determine whether variants of IPNS, IAT, PaaT, PenV, PenM retain their respective catalytic or transport activities.
Although individual assays for protein activity may have been known, the availability of such assays does not provide advance guidance regarding which of the numerous variants within the claimed genera will be functional. The required experimentation would therefore involve extensive trail-and - error screening to identify operative members rather than routine verification of variants reasonably predicted to function.
This deficiency applies to the remaining claimed proteins.
Accordingly, considering the breadth of the claimed protein genera, the limited predictability of retained function based on overall sequence identity, the absence of sufficient structure-function guidance and representative function variants, and the quantity of experimentation required to identify operative members, the specification does not enable the full scope of claims 1, 2, 7, 16, and 19 and the dependent claims 3-6, 8-15, 17-18, and 20-22 without undue experimentation.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 9 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Godtfredsen (1962).
Claim 9 recites a medicinal compound produced from the modified plant, seed, cell, or plant part of claim 1. The product-by-process limitation does not distinguish the claimed product from an identical prior-art product where the product itself is the same.
Godtfredsen discloses fusidic acid (p987), which is one of the medicinal compounds encompassed by claim 9. Claim 9 does not recite a structural or compositional difference between plant-produced fusidic acid and the prior art fucidic acid. Accordingly, Godtfredsen anticipates the claimed medicinal compound.
Claim Rejections - 35 USC § 103
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 1-22 are rejected under 35 U.S.C. §103 as being unpatentable over Petersen (Celine Petersen et. al., IMA Fungus (2023) 14:3, pp1-17) in view of Mattern (Derek J. Mattern et. al., Frontiers in Microbiology (2015) Volume 6, Article 775, pp1-7), and further in view of Dudley (Quentin M. Dudley et. a., Communications biology (2022) 5:949, pp1-12) and Smith (David J. Smith et. al., Bio/Technology (1990) volume 8, pp39–41)
Claim 1 recites a modified plant, seed, cell, or plant part comprising at least one recombinant polynucleotide molecule comprising at least one nucleotide sequence encoding at least one polypeptide having an amino acid sequence with at least about 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:1-6, wherein the modified plant, seed, cell, or plant part is capable of producing a medicinal compound penicillin, for purpose of examination, and consistent with the elected penicillin species.
Claim 1 does not require that a single polynucleotide encode all six polypeptides or that the plant comprise six separate polynucleotides. The limitation “capable of producing penicillin” is interpreted as requiring that the recited plant, seed, cell, or plant part possess the genetic and biochemical capacity to produce penicillin under appropriate expression and culture conditions; it does not require that penicillin be present at a particular concentration, yield, or commercial production level.
Petersen provides genome sequence information for Penicillium species from which the nucleotide sequences corresponding to the claimed proteins are identified (Abstract; p2, left column pa2).
Sequence comparisons using the publicly available Penicillium genome sequence data disclosed by Petersen (NCBI BioProject PRJNA867151) show that the penicillin-pathway proteins identified from the Petersen genome assemblies corresponding to, or share at least about 89% amino acid sequence identity to, the proteins represented by SEQ ID NO: 1-6 (KAJ5265437. 1 shares 98% identity with SEQ ID NO: 1; KAJ5476935.1 shares 93% identity with SEQ ID NO:2; XP_057036050.1 shares 92% identity with SEQ ID NO:3; KAJ5270538.1 shares 99% identity with SEQ ID NO: 4; XP_057144832.1 shares 89% identity with SEQ ID NO: 5; XP_056571215.1 shares 99% identity with SEQ ID NO: 6) (see alignment below). Petersen therefore teaches publicly available nucleotide sequences encoding proteins falling within the claimed sequence-identity scope.
Petersen does not expressly teach introducing the recited penicillin-pathway genes into a plant or plant cell to produce penicillin.
Smith teaches that penicillin biosynthesis from the relevant amino-acid precursors is carried out by three core enzymes: 6-(L-a-amino-adipyl)-L-cysteinyl-o-valine synthetase (ACVS), iso-penicillin N synthetase (IPNS) and acyl coenzyme A:6-aminopenicillanic acid acyltransferase (ACT) (Abstract). ACVS, ACT, and IPNS correspond to SEQ ID NO: 1-3 (Instant application pa0020-0022). Smith therefore establishes the biosynthetic functions of the proteins encoded by the Petersen nucleotide sequences corresponding to SEQ Id NO: 1-3.
Mattern teaches heterologous reconstruction and expression of fungal natural-product biosynthetic pathways and recognizes plants, including tobacco plants, as suitable heterologous hosts for producing natural products (p3, right column pa2). Mattern therefore provides a reason to transfer a known fungal biosynthetic pathway into a plant expression system to obtain the corresponding natural product.
Dudley further teaches that Nicotiana benthamiana is a suitable host for metabolic-pathway reconstitution and demonstrates successful reconstitution of strictiosidine biosynthesis from central plant metabolism by co-expression of fourteen heterologous enzymes (Abstract). Dudley reports that co-expression of the complete pathway produced the intended natural product , strictiosidine (Fig 4, 5, 6). Dudley further confirms that co-infiltration of strains expressing the entire pathway produced a product peak matching an authentic strictosidine standard and resulted in a measurable amount of strictosidine in Nicotiana Benthamiana leaf tissue (p9, right column pa2; Supplementary table 7).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to introduce the Petersen nucleotide sequences encoding ACVS, ACT, and IPNS into a plant or plant cell because Smith teaches that these enzymes provide the core enzymatic activities required for biosynthesis of penicillin from the relevant precursors, Mattern identifies plants as suitable heterologous hosts for fungal natural-product pathways, and Dudley demonstrates successful expression of a complex heterologous biosynthetic pathway in Nicotiana benthamiana. A person of ordinary skill would have been motivated to make this modification to use plants as an alternative biosynthetic chassis for production of a valuable fungal natural product and to obtain the scalability and production advantages associated with plant expression system.
A person of ordinary skill would have had a reasonable expectation of success because Dudley demonstrates that a complex heterologous biosynthetic pathway involving fourteen co-expressed enzymes can function in N. benthamiana and produce its intended small-molecule products.
Accordingly, claim 1 would have been obvious over Petersen in view of Mattern, Smith and Dudley.
Claim 2 recites the modified plant, seed, cell, or plant part of claim 1, wherein the plant, seed, cell, or plant part comprises: a) having at least about 85% sequence identity to SEQ ID NO: 1-6, respectively, wherein the modified plant material is capable of producing penicillin. Claim 3 recites the modified plant, seed, cell, or plant part of claim 1, wherein the at least one recombinant polynucleotide molecule comprises at least one nucleotide sequence encoding at least one polypeptide having an amino acid sequence with at least about 90%-100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:1-6. Claim 4 recites the modified plant, seed, cell, or plant part of claim 1, wherein the modified plant, seed, cell, or plant part comprises at least one polypeptide having an amino acid sequence with at least about 90%-100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:1-6. Claim 5 recites the modified plant, seed, cell, or plant part of claim 4, wherein the modified plant, seed, cell, or plant part comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, or at least twelve polypeptides having an amino acid sequence with at least about 90%-100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:1-107. Claim 6 recites modified plant, seed, cell, or plant part of claim 1, wherein the modified plant, seed, cell, or plant part comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, or at least twelve recombinant polynucleotide molecules. Claim 7 recites the modified plant, seed, cell, or plant part of claim 1, wherein the modified plant, seed, cell, or plant part comprises: a) at least two to at least six polypeptides having an amino acid sequence with at least about 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-6, wherein the modified plant, seed, cell, or plant part is capable of producing penicillin; Claim 9 recites a medicinal compound produced from the modified plant, seed, cell, or plant part of claim 1. Claim 12 recites the modified plant, seed, cell or plant part of claim 1, wherein the modified plant, seed, cell, or plant part is a Nicotiana benthamiana, a corn, or a soybean plant, seed, cell, or plant part.
For the same reason set forth above with respect to claim 1, Sequence comparisons using the publicly available Penicillium genome sequence data disclosed by Petersen show that the identified proteins share about 89-99% amino acid sequence identity with the respective proteins represented by SEQ ID NO: 1-6. In particular, at least five of the identified proteins share at least 90% amino acid sequence identity with their respective SEQ ID NOs and therefore fall within the sequence-identity scope of claims 3 and 4. Petersen further provides at least six nucleotide sequences encoding respective proteins within the claimed sequence-identity scope. Thus, the proposed plant or plant cell comprising the Petersen penicillin-pathway sequences would comprise at least two qualifying polypeptides and at least two recombinant polynucleotide molecules, as required by claims 5 -7.
With respect to claim 9, penicillin is a medicinal compound, and the modified plant, seed, cell, or plant part resulting from the proposed combination would produce penicillin for the reasons discussed above with respect to claim 1.
With respect to claim 12, Dudley further teaches de novo production of strictosidine in N. benthamiana through expression of a multienzyme heterologous biosynthetic pathway and the generation of transgenic plant lines (p2, right column, pa2).
Accordingly, Claims 2-7, 9, and 12 would have been obvious over Petersen in view of Mattern, Smith and Dudley.
Claim 8 recites a plant commodity product produced from the modified plant, seed, cell, or plant part of claim 1, wherein said plant commodity product comprises said at least one recombinant polynucleotide molecule.
Claim 8 is interpreted as requiring a plant commodity product that is produced from the modified plant or plant par of claim 1, and contains the recombinant polynucleotide molecule recited in claim 1.
For the same reason set forth above with respect to claim 1, Dudley further teaches the genetically modified Nicotiana benthamiana plants producing strictosidine in harvested leaf tissue, including a reported a yield of 0.23 +/- 0.11 mg strictosidine per gram dry weight leaf tissue (p5, right column, pa2; p8, left column, pa3). Dudley therefore teaches obtaining harvested plant tissue from a genetically modified plant expressing a heterologous biosynthetic pathway. Because the harvested leaf tissue is derived from the genetically modified plant tissue expressing the introduced pathway, the harvested tissue contains the introduced recombinant polynucleotide molecules. It would therefore have been obvious to obtain a plant commodity product, such as harvested leaf tissue, from the modified penicillin-producing plant of claim 1, with the plant commodity product containing at least one of the introduced recombinant polynucleotide molecules.
Claim 8 would have been obvious over Petersen in view of Mattern, Smith and Dudley.
Claim 10 recites the modified plant, seed, cell, or plant part of claim 1, wherein the at least one recombinant polynucleotide molecule comprises a heterologous promoter functional in a plant cell. Claim 11 recite the modified plant, seed, cell, or plant part of claim 1, wherein the at least one recombinant polynucleotide molecule comprises a targeting nucleotide sequence or encodes a targeting polypeptide sequence.
Dudley taches using CaMV 35 s promoter (CaMV35s) for construction of expression constructs (pa9, “Construction of expression constructs”). Dudley further teaches expression constructs comprising, when required, a synthetic chloroplast transit peptide sequence to alter the subcellular localization of the encoded protein(pa9, “Construction of expression constructs”). A chloroplast transit peptide is a targeting polypeptide sequence because it direct the encoded protein to the chloroplast.
Accordingly, Claims 10-11 would have been obvious over Petersen in view of Mattern, Smith and Dudley.
Claim 13 recites a method for producing a modified plant cell, the method comprising introducing at least one heterologous polynucleotide molecule into a plant cell, wherein said heterologous polynucleotide molecule comprises at least one nucleotide sequence encoding at least one polypeptide having an amino acid sequence with at least about 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:1-6.
For the same reason set forth above with respect to claim 1, it would have been obvious to introduce the Petersen nucleotide sequences encoding the claimed proteins into a plant cell, as taught by Mattern and Dudley and with the reasonable expectation of success discussed above.
Accordingly, Claim 13 would have been obvious over Petersen in view of Mattern, Smith and Dudley.
Claim 14 recites the method of claim 13, the method further comprising selecting at least one plant cell comprising said at least one heterologous polynucleotide molecule. Claim 15 recites the method of claim 13, the method further comprising regenerating at least one modified plant or plant part from the at least one selected plant cell or a descendant thereof comprising said at least one heterologous polynucleotide molecule. Claim 16 recites the method of claim 15, wherein the modified plant or plant part comprise a firs through sixth nucleotide sequence encoding polypeptides having at least about 85% sequence identity to SEQ ID NO: 1-6, respectively, wherein the modified plant or plant part is capable of producing penicillin. Claim 17 recites the method of claim 13, wherein the at least one heterologous polynucleotide molecule comprises at least one nucleotide sequence encoding at least one polypeptide having an amino acid sequence with at least about 90% to 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:1-6. Claim 18 recites the method of claim 13, the method comprising introducing at least two, to at least twelve heterologous polynucleotide molecules into said plant cell. Claim 19 recites the method of claim 15, wherein the modified plant or plant part comprises: a) at least two, to at least six polypeptides having an amino acid sequence with at least about 85% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-6, wherein the modified plant, seed, cell, or plant part is capable of producing penicillin. Claim 22 recites the method of claim 13, wherein the plant cell is a Nicotiana benthamiana, a corn, or a soybean plant cell.
For the same reason set forth above with respect to claims 1-6, and 13, Claim 14-19, and 22 would have been obvious over Petersen in view of Mattern, Smith and Dudley.
Claim 20 recites the method of claim 13, wherein the at least one heterologous polynucleotide molecule comprises a promoter functional in a plant cell. Claim 21 recites the method of claim 13, wherein the at least one heterologous polynucleotide molecule comprises a targeting nucleotide sequence or encodes a targeting polypeptide sequence.
For the same reason set forth above with respect to claims 1, 10, 11, and 13, Dudley taches using CaMV 35 s promoter (CaMV35s) for construction of expression constructs. Dudley further teaches expression constructs comprising, when required, a synthetic chloroplast transit peptide sequence to alter the subcellular localization of the encoded protein.
Accordingly, claims 20-21 would have been obvious over Petersen in view of Mattern, Smith and Dudley.
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Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YANXIN SHEN whose telephone number is (571)272-7538. The examiner can normally be reached Monday-Friday.
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/YANXIN SHEN/ Examiner, Art Unit 1663
/WEIHUA FAN/ Primary Examiner, Art Unit 1663
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