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 .
DETAILED ACTION
1. Applicant’s election of Group I (claims 1-5) without traverse in the reply filed on 1/16/26 is acknowledged.
2. Claims withdrawn:
Claims 6, 8-11, 13-14, 18 & 20-22 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
3. Priority
Applicant’s claim for domestic priority under 35 U.S.C. 119(e), filed 4/19/19, is acknowledged.
4. Drawings filed 6/28/23 are acknowledged.
5. IDS files 6/28/23 is acknowledged. A signed copy of the IDS is provided with this Office Action.
6. 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 1-4 and 5 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by 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 claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Scope of the claimed genus
Claim 1 is drawn to a recombinant S. cerevisiae cell comprising a polynucleotide encoding Pyp1, ortholog thereof, or a variant of Pyp1 at least 70% identical to the amino acid sequence of SEQ ID NO: 1, wherein the polynucleotide is operably linked to a heterologous promoter.
Claim 2 is drawn to a recombinant microorganism comprising a polynucleotide encoding Pyp1, ortholog thereof, or a variant of Pyp1 at least 70% identical to the amino acid sequence of SEQ ID NO: 1.
The subject of this rejection is the recitation of “comprising a polynucleotide encoding Pyp1, ortholog thereof, or a variant of Pyp1 at least 70% identical to the amino acid sequence of SEQ ID NO: 1”. The claims encompass polynucleotides encoding thousands of different orthologs of Pyp1 and variants of SEQ ID NO: 1.
Assessment of whether species are disclosed in the original specification
The Specification only describes instances in which a polynucleotide encodes a Pyp1 having SEQ ID NO: 1. The Specification does not describe any other orthologs of Pyp1 or variants of SEQ ID NO: 1.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the Specification describes a polynucleotide which encodes a Pyp1 having SEQ ID NO: 1. There are thousands of possible orthologs of Pyp1 and variants of SEQ ID NO: 1. The Specification, however, does not describe any other orthologs of Pyp1 or variants of SEQ ID NO: 1 other than the Pyp1 having SEQ ID NO: 1.
Identifying characteristics and structure/function correlation
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by 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 claimed genus. To meet this requirement in the instant case, the specification must describe the structural, physical and/or chemical properties of orthologs of Pyp1 and variants of SEQ ID NO: 1 and the functional characteristics of such orthologs and variants, i.e., the ability to act as a polyol phosphatase. The specification does not describe physical and/or chemical properties of any orthologs of Pyp1 or variants of SEQ ID NO: 1. The specification also does not describe a correlation between the structure of the claimed orthologs of Pyp1 and variants of SEQ ID NO: 1 that allow for polyol phosphatase activity. The specification only describes instances in which a polynucleotide encodes a Pyp1 having SEQ ID NO: 1. Accordingly, the specification fails to provide guidance on the specific structural features of the genus that account for the function of the genus, namely what portions and variations of orthologs and variants of SEQ ID NO: 1 that allow for polyol phosphatase activity. Absent this information, the skilled artisan cannot readily envisage specific embodiments of orthologs of Pyp1 and variants of SEQ ID NO: 1 that possess the relevant functional properties.
In conclusion, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the invention with respect to recombinant microorganisms which comprise the claimed orthologs of Pyp1 and variants of SEQ ID NO: 1.
7. 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.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuznetsova et al. (Journal of Biological Chemistry, 290(30): 18678-18698, 2015, see IDS filed 6/28/23).
Kuznetsova et al. describe studies of phosphatases from Saccharomyces cerevisiae (abstract). One of the phosphatases studied was YNL010W, which is the phosphatase which corresponds to the phosphatase having SEQ ID NO: 1 of the present application (Table 1). The polynucleotide encoding YNL010W was cloned, incorporated into the vector pET15b, and expressed in Escherichia coli (pages 18679-18680 under “Gene Cloning, Protein Purification, and Mutagenesis”).
8. Claim(s) 1-3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yi-Fan Xu, et al. (ACS Chem. Biol. 2018, 13, 3011−3020).
Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yi-Fan Xu, et al.
Claims 1-5 are drawn to as follows-
1. (Original) A recombinant S. cerevisiae cell comprising a polynucleotide encoding Pyp1, ortholog thereof, or a variant of Pyp1 at least 70% identical to the amino acid sequence of SEQ ID NO: 1, wherein the polynucleotide is operably linked to a heterologous promoter.
2. (Original) A recombinant microorganism comprising a polynucleotide encoding Pyp1, ortholog thereof, or a variant of Pyp1 at least 70% identical to the amino acid sequence of SEQ ID NO: 1.
3. (Original) The recombinant microorganism of claim 2, wherein the microorganism is a fungus or a bacteria.
4. (Original) The recombinant microorganism of claim 3, wherein the fungus is S. cerevisiae.
5. (Original) The recombinant microorganism of claim 2, wherein the microorganism further comprises a polynucleotide encoding an enzyme with sugar phosphate dehydrogenase activity operably linked to a heterologous promoter.
Yi-Fan Xu, et al (see, for example, abstract, introduction & experimental procedures and the full text) teach the molecular cloning, biochemical characterization and show that the yeast gene YNL010W, which has close homologues in all fungi species and some plants, encodes a sugar alcohol phosphatase. We term this enzyme, which hydrolyzes sorbitol-6-phosphate, ribitol-5-phosphate, and (D)-glycerol-3-phosphate, polyol phosphatase 1 or PYP1. See Figures 2-5, for example, for the specific properties and characterization of the PYP1.
Protein Purification and Enzymatic Assays. For Pyp1’s polyol phosphatase activity assay, a yeast Open Reading Frame (ORF) strain with an expression vector containing C-terminal His-tagged PYP1 (Open Biosystems, Thermo Fisher Scientific, San Jose, CA) was grown on galactose to induce Pyp1 expression. The resulting cells were lysed using glass beads, and His-tagged Pyp1 was purified using Qiagen Ni-NTA spin columns according to the manufacturer’s instructions. Phosphatase activity against ribitol-5-phosphate, sorbitol-6-phosphate, erythritol-4-phosphate, and octulose-8-phosphate was determined by monitoring the increase of ribitol, sorbitol, erythritol, or octulose using LC-MS. The reaction mixture contained 100 mM Tris-HCl at the pH 8.0, 10. The Pyp1 purified appears to be no different than the Applicants’ SEQ ID NO: 1. See page 3017, column 2, paragraph 2 for example.
The reference anticipates the claims.
This appears to be Applicant’s own work, the reference can be overcome by filing a Katz's declaration.
9. 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 1-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ladero et al. (Applied Environmental Microbiology, 73(6): 1864-1872, 2007 – see IDS filed 6/28/23) in view of Kuznetsova et al. (Journal of Biological Chemistry, 290(30): 18678-18698, 2015).
Ladero et al. describe genetically modified Lactobacillus plantarum for producing sorbitol (abstract). Enhanced sorbitol production resulted in L. plantarum which was modified to overexpress two sorbitol-6-phosphate dehydrogenase genes (Tables 1 and 2). Figure 1 shows that sorbitol-6-phosphate results from the action of sorbitol-6-phosphate dehydrogenase on fructose-6-phosphate, and that sorbitol is formed by dephosphorylation of sorbitol-6-phosphate.
Kuznetsova et al. describe studies of phosphatases from Saccharomyces cerevisiae (abstract). One of the phosphatases studied is YNL010W, which is the phosphatase which corresponds to the phosphatase having SEQ ID NO: 1 of the present application (Table 1). The polynucleotide encoding YNL010W was cloned, incorporated into the vector pET15b, and expressed in Escherichia coli (pages 18679-18680 under “Gene Cloning, Protein Purification, and Mutagenesis”). Table 1 shows that YNL010W is able to use sorbitol-6-phosphate as a substrate.
It would have been obvious to have overexpressed the YNL010W of Kuznetsova et al. in the genetically modified L. plantarum of Ladero et al. because Ladero et al. show that sorbitol is produced in L. plantarum due to dephosphorylation of sorbitol-6-phosphate and the ability of YNL010W to dephosphorylate sorbitol-6-phosphate, as shown by Kuznetsova et al., would be expected to enhance the production of sorbitol by the Ladero bacterium. Alternatively, it would have been obvious to one of ordinary skill in the art to have used Saccharomyces cerevisiae as the host cell for genetic modification because fructose-6-phosphate is also a metabolic intermediate in S. cerevisiae and, thus, S. cerevisiae would also be expected to produce sorbitol if genetically modified to overexpress YNL010W and sorbitol-6-phosphate dehydrogenase.
10. 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 2 is rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 2 does not recite something significantly different than a judicial exception. Claim 2 encompass a naturally-occurring microorganism, whether isolated, synthetic or recombinant or not, that are not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., 106 USPQ2d 1972 (June 13, 2013) as they are not markedly different than the Saccharomyces cerevisiae comprising the polynucleotide having SEQ ID NO: 1 as it occurs in nature.
11. Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Xu et al. ACS Chem. Biol. 2018, 13, 3011−302022.
12. No claim is allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940