DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20 are pending in the instant application.
Applicant’s election of Group I (Invention I) and SEQ ID NO: 1 in the reply filed on 07/29/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)). Upon consideration of the election dated 07/29/2025, SEQ ID NO: 3 will also be examined.
Claims 3-5, 10-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The requirement is still deemed proper and is therefore made FINAL.
Claims 1, 2, 6-9, 19, 20 and SEQ ID NOs: 1 and 3 are under consideration in this Office Action.
Claim Objection(s)
Claim 1 is objected to reciting NB-2Ni peptide without defining the abbreviation “NB-2Ni”.
Claim Rejections - 35 U.S.C. § 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.
Claims 1, 2 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim recite a naturally occurring protein that is a product of nature. This judicial exception is not integrated into a practical application because no other meaningful limitations are recited in the claims. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons stated below.
The claims encompass a naturally occurring peptide of any amino acid sequence and structure comprising at least 13 amino acids coordinating a di-nickel cluster which catalyzes production of H2 in the presence of a suitable electron donor, which is a naturally occurring protein.
Peters et al. (Biochim. Biophys. Acta—Mol. Cell Res. 1853, 1350-1369, 2015; IDS filed 08/29/2023) reviews and compares naturally occurring hydrogen-producing enzymes of [FeFe] hydrogenases and [NiFe] hydrogenases; their active sites incorporate non-protein ligands, specifically carbon monoxide and cyanide, and bound to iron atoms where these ligands are crucial for enzyme reactivity. The claimed peptide are deemed to be naturally occurring protein containing active sites present in naturally occurring hydrogen-producing enzymes of [FeFe] hydrogenases and [NiFe] hydrogenases.
The claim does not recite any additional elements other than a naturally-occurring protein that may be purified or in aqueous solution in some embodiments. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed protein are not markedly different form the naturally occurring counterpart because it conveys the same structural and functional information and the claim do not recite any additional features that could add significantly more to the exception. Accordingly, the claim does not qualify as eligible subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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, 2, 6-9, 19, 20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a broad and widely varying genus of NB-2Ni peptides of any amino acid sequence and structure comprising at least any 13 amino acids coordinating a di- nickel cluster which catalyzes production of H2 in the presence of a suitable electron donor. According to MPEP 2163:
“For each claim drawn to a genus: 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 (see i)(A), above), reduction to drawings (see i)(B), above), 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 (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…”
According to MPEP 2163.02:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; PTO 892) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; PTO 892) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). The reference teachings only provide guidance for searching and screening for the genus of NB-2Ni peptides.
The specification as originally filed does not disclose a representative number of species encompassed by the claimed genus by actual reduction to practice. The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict which amino acid sequences and structures correlate with the recited genus of NB-2Ni peptides having the ability to catalyze production of H2 in the presence of a suitable electron donor.
Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants were in possession at the time the application was filed of the claimed varying genus of NB-2Ni peptides of any amino acid sequence and structure comprising at least any 13 amino acids coordinating a di- nickel cluster which catalyzes production of H2 in the presence of a suitable electron donor.
For examination purposes, the recited NB-2Ni peptide will be not limited to a specific amino acid sequence and structure.
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 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 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Accession A0A077M4L6 (29-OCT-2014; PTO 892).
For the reasons stated above, the recited NB-2Ni peptide will be not limited to a specific amino acid sequence and structure.
Accession A0A077M4L6 teaches a peptide having an amino acid sequence that is 100% identical to SEQ ID NO: 1 of the instant application (see attached record). Since the amino acid sequence of the peptide of Accession A0A077M4L6 has an amino acid sequence that is 100% identical to SEQ ID NO: 1, then the peptide would inherently coordinate a di- nickel cluster and catalyze production of H2 in the presence of a suitable electron donor. Thus, the reference teachings anticipate the claimed invention.
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 of this title, 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, 2, 6-9, 19, 20 are rejected under 35 U.S.C. 103 as being unpatentable over
Accession A0A077M4L6 (29-OCT-2014; PTO 892) in view of US20120083599A1 (04/05/2012; PTO 892), Eilenberg et al. (Biotechnol Biofuels (2016) 9:182; PTO 892),
Shen et al. (J. Mater. Chem. A, 2020, 8, 485; PTO 892), US20170137764A1 (05/18/2017; PTO 892), US20120322911A1 (12/20/2012; PTO 892), Peters et al. ([FeFe]- and [NiFe]-hydrogenase diversity, mechanism, and maturation (Biochim. Biophys. Acta—Mol. Cell Res. 1853, 1350-1369, 2015; IDS filed 08/29/2023), Esmieu et al. (Sustainable Energy Fuels, 2018, 2, 724; PTO 892), Bornscheuer et al. (Curr Protoc Protein Sci. 2011 Nov;Chapter 26:Unit26.7; PTO 892).
Accession A0A077M4L6 teaches a peptide having an amino acid sequence that is 100% identical to SEQ ID NO: 1 of the instant application (see attached record). Since the amino acid sequence of the peptide of Accession A0A077M4L6 has an amino acid sequence that is 100% identical to SEQ ID NO: 1, then the peptide would inherently coordinate a di- nickel cluster and catalyze production of H2 in the presence of a suitable electron donor. The teachings of the reference differ from the claims in that the reference does not teach the peptide fused to biotin, a system comprising the peptide and an electron donor, and a bioreactor for producing hydrogen recited in the claims.
US20120083599A1 teaches biotin and biotin analogues, and methods for labeling target structures and biomolecules including such as peptides and proteins in vitro or in vivo (see entire publication and claims especially claims 1 and 34 and paragraphs [0012]- [0039]).
Eilenberg et al. teaches the fusion of the electron carrier ferredoxin (Fd) and the hydrogenase enzyme (HydA), creating one continuous "fusion protein" (Fd-HydA), where by linking Fd to HydA the electrons coming from photosynthesis are channeled directly to the hydrogenase giving it a fast lane that bypasses the competing FNR enzyme, and rate of H₂ production increased significantly by about 4.5 times compared to the native, unfused proteins (see entire publication and abstract especially Results section, Discussion section and pages 2-7).
Shen et al. teaches the dehydrobenzoannulene-based three dimensional graphdiyne for photocatalytic hydrogen generation using Pt nanoparticles as a co-catalyst and triethanolamine (TEOA) as a sacrificial electron donor to boost H2 generation (see entire publication and abstract especially Results and discussion section and pages 4850-54).
US20170137764A1 teaches light-emitting diode (LED) photobioreactors and methods of use, specifically for optimizing the cultivation of photosynthetic organisms by using specific light wavelengths (see entire publication and claims especially claims 1-9).
US20120322911A1 teaches polyimide gas separation membranes with high permeances and selectivities for gas separations, particularly for CO₂/CH₄ and H₂/CH₄ separations (see entire publication and claims especially claims 1-16).
Peters et al. reviews and compares the distinct types of hydrogen-producing enzymes of [FeFe] hydrogenases and [NiFe] hydrogenases; their active sites incorporate non-protein ligands, specifically carbon monoxide and cyanide, bound to iron atoms where these ligands are crucial for enzyme reactivity; and processes required to build these unique active sites (see entire publication and abstract especially 3.Hydrogenase mechanism section, 4. Maturation section, Figs. 4-9, and pages 1356-1363)
Esmieu et al. reviews efforts on engineering and optimizing hydrogenase enzyme for biological hydrogen gas production, where while the entire enzyme is large and complex, the crucial part is the small, embedded metal-containing active site where hydrogen is made or consumed which is known for [NiFe] and [FeFe] enzymes (see entire publication and abstract especially 2. Hydrogenases section to 4. Synthetic catalysts section and pages 726-40)
Bornscheuer et al. teach protein engineering strategies to improve or change the properties of proteins, teach concepts for protein engineering using rational design including substitution and/or deletion of amino acids, directed evolution, and combinations of them where different strategies are presented for identifying the best mutagenesis method, how to identify desired variants by screening or selection, and examples for successful applications are shown which enable researchers to choose the most promising tools to solve their protein engineering challenges (see entire publication especially pages 26.7.1- 26.7.10 and Tables 26.7.1, 26.7.2, and 26.7.3).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by making a fusion peptide comprising the peptide of Accession A0A077M4L6 with the electron carrier ferredoxin (Fd) of Eilenberg et al. in an aqueous solution, making a fusion peptide comprising the peptide of Accession A0A077M4L6 with the biotin or biotin analog as taught by US20120083599A1 in an aqueous solution to arrive at the amino acid sequence of SEQ ID NO: 14 or 15, and making a system comprising the peptide of Accession A0A077M4L6 and triethanolamine (TEOA) sacrificial electron donor of Shen et al. in an aqueous solution. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a peptide that catalyzes production of H2 in the presence of a suitable electron donor including TEOA. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the photobioreactors of US20170137764A1 to contain the gas separation membranes of US20120322911A1 and then adding a suspension of the system comprising the peptide of Accession A0A077M4L6 and triethanolamine (TEOA) sacrificial electron donor to the photobioreactor for production and separation of hydrogen produced by the system. In view of the reference teachings of Peters et al., Esmieu et al., and Bornscheuer et al., it would have been obvious to modify the peptide of Accession A0A077M4L6 to obtain any of the peptides recited in the application comprising the amino acid sequence of any of SEQ ID NOs: 1-13 that coordinates a di- nickel cluster which catalyzes production of H2 in the presence of a suitable electron donor. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because modifying hydrogenases for producing H2 in the presence of a suitable electron donor are known in the art as shown by the reference teachings. Hence, the claimed invention as a whole is prima facie obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christian L Fronda whose telephone number is (571)272 0929. The examiner can normally be reached Monday-Thursday and alternate Fridays between 9:00AM-5:00PM.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on (408)918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652