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
This application is a 371 of PCT/EP2022/058082.
The amendment filed on June 2, 2026 has been entered. No new matter has been added.
Election/Restrictions
Applicant’s election of Group I with a species election of (1) Novosphingobium aromaticivorans as the microorganism and (2) a recombinant γ-formaldehyde lyase gene encoding PcfL of Novosphingobium aromaticivorans (SEQ ID NO: 16) as the recombinant gene in the reply filed on April 2, 2026 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 § 818.01(a)).
Claims 2-9, 12-15, and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (claims 2-9 and 12-15) and invention (claim 19), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 2, 2026.
Status of Claims
Claims 1-19 and 21.
Claims 2-9, 12-15, and 19 are withdrawn.
Claims 1, 10-11, 16-18, and 21 are under examination.
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 1, 11, and 21 and claims 10 and 15-18 depending therefrom 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.
Claims 1, 11, and 21 recite the phrase “(SEQ ID NO:16)”. The phrase "(SEQ ID NO:16)" renders the claim indefinite because it is unclear whether the limitation(s) enclosed in the parentheses are part of the claimed invention. See MPEP § 2173.05(d). Clarification is requested.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 11 recites the phrase “wherein, when present..”. Claim 11 recites only contingent limitations and therefore do not further limit claim 10.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 10-11, 16-18, and 21 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.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' The claims have been broadly interpreted to encompass (A) any recombinant microorganism, any bacterium, any Alphaproteobacterium, any Sphingomonoadales, or Novosphingobium aromaticivorans comprising (B) a recombinant Novosphingobium aromaticivorans γ-formaldehyde lyase gene encoding PcfL and any homolog/ortholog/any variant thereof, Novosphingobium aromaticivorans γ-formaldehyde lyase gene encoding PcfL having the amino acid sequence of SEQ ID NO:16 any homolog/ortholog thereof, and any protein having at least 95-99% sequence identity to SEQ ID NO:16 and having unknown function. Therefore, the claims are drawn to (A) a genus of microorganism comprising (B) a genus of γ-formaldehyde lyase genes encoding γ-formaldehyde lyase having the amino acid sequence of SEQ ID NO:16 or having unknown structure or a genus of proteins having at least 95-99% sequence identity to SEQ ID NO:16 but having unknown function.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The recitations of “PcfL”, “γ-formaldehyde lyase”, “homolog”, “ortholog”, and “protein” fail to provide a sufficient description of the genus of the enzymes used in the claimed method as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus.
Kuatsjah (Biochemical and structural characterization of a sphingomonad diarylpropane lyase for cofactorless deformylation. Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2212246120. doi: 10.1073/pnas.2212246120. Epub 2023 Jan 18. – form PTO-892) discloses a Novosphingobium aromaticivorans gene encoding a γ-formaldehyde lyase Saro_2805 (NaLdpA) and Saro_0796, which are homologs of Novosphingobium aromaticivorans gene encoding a γ-formaldehyde lyase (PcfL) (page 2, 4th full paragraph and Figure S1 at page 9 of the Supplementary Information).
However, Novosphingobium aromaticivorans gene encoding a γ-formaldehyde lyase (PcfL) having the amino acid sequence of SEQ ID NO:16 was not known.
The specification is limited to a recombinant Novosphingobium aromaticivorans comprising a gene encoding the γ-formaldehyde lyase having the amino acid sequence of SEQ ID NO:16. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, the examples described above is not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus.
Regarding claims 11 and 21, the claims encompass many functionally unrelated polypeptides encompassed within the scope of these clams, including partial sequences, resulting in a substantial variation within the genus. The genus of these polypeptides comprise a large variable genus with the potentiality of having different activity or no activity. The specification only describes one species, γ-formaldehyde lyase having the amino acid sequence of SEQ ID NO:16. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, this one example is not enough and does not constitute a representative number of species to describe the whole genus of proteins having unknown function and there is no evidence on the record of the relationship between the structure of the γ-formaldehyde lyase of SEQ ID NO:16 and the structure of any protein having at least 95-99% sequence identity to SEQ ID NO:16 and having γ-formaldehyde lyase activity. The specification also fails to describe additional representative species of the polypeptides by any identifying characteristics or properties of the polypeptides, for which no predictability of function is apparent. Therefore, one skilled in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
Further, one of skill in the art could identify variants of SEQ ID NO:16. However, there is no teaching regarding which amino acids of SEQ ID NO:16 can vary and result in a polypeptide having γ-formaldehyde lyase activity. Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
An important consideration is that structure is not necessarily a reliable indicator of function. In the instant case, there is no disclosure relating similarity of structure to conservation of function. Conservation of structure is not necessarily a surrogate for conservation of function.
Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the inventions of claims 1, 10-11, 16-18, and 21.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 10-11, 16-18, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kuatsjah (Biochemical and structural characterization of a sphingomonad diarylpropane lyase for cofactorless deformylation. Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2212246120. doi: 10.1073/pnas.2212246120. Epub 2023 Jan 18. – form PTO-892) and Linz (iNovo479: Metabolic Modeling Provides a Roadmap to Optimize Bioproduct Yield from Deconstructed Lignin Aromatics by Novosphingobium aromaticivorans. Metabolites. 2022 Apr 18;12(4):366 – form PTO-892).
Regarding claims 1 and 10-11, Kuatsjah discloses a Novosphingobium aromaticivorans gene encoding a γ-formaldehyde lyase Saro_2805 (NaLdpA), Saro_0796, and SpLdpA, which are homologs/ortholog of Novosphingobium aromaticivorans gene encoding a γ-formaldehyde lyase (PcfL) (page 2, 4th full paragraph and Figure S1 at page 9 of the Supplementary Information). Kuatsjah also discloses a Sphingobium sp. SYK-6 γ-formaldehyde lyase, which is a ortholog of
Regarding claims 11 and 21, Saro_0796 has at least 99% sequence identity to SEQ ID NO:6 of the instant application (Figure S1 at page 9 of the Supplementary Information and see the sequence alignment below).
Kuatsjah does not disclose a recombinant Novosphingobium aromaticivorans comprising the above homologs.
Kuatsjah discloses that LdpA is the first enzyme lignin valorization, producing ring-opened lignin-derived dimers (abstract).
Regarding claims 16-18 and 21, Linz discloses that Novosphingobium aromaticivorans is used as a bacterial chassis for lignin valorization (abstract). Linz discloses metabolic engineering of Novosphingobium aromaticivorans (Section 2.7).
Therefore, in combing the teachings of the above references, it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to engineer a recombinant Novosphingobium aromaticivorans comprising a gene encoding the γ-formaldehyde lyase homolog Saro_2805 (NaLdpA), Saro_0796, or SpLdpA. One of ordinary skill in the art would have been motivated to do so for lignin valorization. One of ordinary skill in the art would have had a reasonable expectation of success since Linz discloses that Novosphingobium aromaticivorans is used as a bacterial chassis for lignin valorization and Kuatsjah discloses γ-formaldehyde lyase and homologs/ortholog, which is the first enzyme lignin valorization, producing ring-opened lignin-derived dimers.
Therefore, the above references render claims 1, 10-11, 16-18, and 21 prima facie obvious.
Conclusion
Claims 1-19 and 21 are pending.
Claims 2-9, 12-15, and 19 are withdrawn.
Claims 1, 10-11, 16-18, and 11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YONG D PAK whose telephone number is (571)272-0935. The examiner can normally be reached M-Th: 5:30 am - 3:30 pm.
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.
/YONG D PAK/Primary Examiner, Art Unit 1652
Sequence alignment of the γ-formaldehyde lyase of SEQ ID NO:16 of the instant application (“Qy”) and the γ-formaldehyde lyase “Saro_0796” of Kuatsjah (“Db”)
Q2GA82_NOVAD
ID Q2GA82_NOVAD Unreviewed; 246 AA.
AC Q2GA82;
DT 21-MAR-2006, integrated into UniProtKB/TrEMBL.
DT 21-MAR-2006, sequence version 1.
DT 02-APR-2025, entry version 74.
DE RecName: Full=SnoaL-like domain-containing protein {ECO:0000259|Pfam:PF13577};
GN OrderedLocusNames=Saro_0796 {ECO:0000313|EMBL:ABD25241.1};
OS Novosphingobium aromaticivorans (strain ATCC 700278 / DSM 12444 / CCUG
OS 56034 / CIP 105152 / NBRC 16084 / F199).
OC Bacteria; Pseudomonadati; Pseudomonadota; Alphaproteobacteria;
OC Sphingomonadales; Sphingomonadaceae; Novosphingobium.
OX NCBI_TaxID=279238 {ECO:0000313|EMBL:ABD25241.1, ECO:0000313|Proteomes:UP000009134};
RN [1] {ECO:0000313|Proteomes:UP000009134}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700278 / DSM 12444 / CCUG 56034 / CIP 105152 / NBRC 16084
RC / F199 {ECO:0000313|Proteomes:UP000009134};
RG US DOE Joint Genome Institute;
RA Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C., Glavina T.,
RA Hammon N., Israni S., Pitluck S., Chain P., Malfatti S., Shin M.,
RA Vergez L., Schmutz J., Larimer F., Land M., Kyrpides N., Ivanova N.,
RA Fredrickson J., Balkwill D., Romine M.F., Richardson P.;
RT "Complete sequence of Novosphingobium aromaticivorans DSM 12444.";
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
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DR EMBL; CP000248; ABD25241.1; -; Genomic_DNA.
DR RefSeq; WP_011444455.1; NC_007794.1.
DR AlphaFoldDB; Q2GA82; -.
DR STRING; 279238.Saro_0796; -.
DR KEGG; nar:Saro_0796; -.
DR eggNOG; ENOG5032MJ0; Bacteria.
DR HOGENOM; CLU_072640_0_0_5; -.
DR Proteomes; UP000009134; Chromosome.
DR Gene3D; 3.10.450.50; -; 1.
DR InterPro; IPR032710; NTF2-like_dom_sf.
DR InterPro; IPR037401; SnoaL-like.
DR Pfam; PF13577; SnoaL_4; 1.
DR SUPFAM; SSF54427; NTF2-like; 1.
PE 4: Predicted;
KW Reference proteome {ECO:0000313|Proteomes:UP000009134}.
FT DOMAIN 25..163
FT /note="SnoaL-like"
FT /evidence="ECO:0000259|Pfam:PF13577"
SQ SEQUENCE 246 AA; 28969 MW; 423E1E893C528244 CRC64;
Query Match 99.8%; Score 1367; Length 246;
Best Local Similarity 99.6%;
Matches 245; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VSDSNQIAALESRLNDLERRLTVREDELDVRKLQHLYGYLIDKCMYNETVDLFTEDGEVR 60
:|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSDSNQIAALESRLNDLERRLTVREDELDVRKLQHLYGYLIDKCMYNETVDLFTEDGEVR 60
Qy 61 FFGGVWKGKEGIRRLYVERFQKRFTYGNNGPIDGFLLDHPQLQDIIHVQDDGVTALGRAR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FFGGVWKGKEGIRRLYVERFQKRFTYGNNGPIDGFLLDHPQLQDIIHVQDDGVTALGRAR 120
Qy 121 SMMQAGRHKDYEGDAPHLKARQWWEGGIYENTYKKVDGVWRMHILNYMPIWHADFESGWA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SMMQAGRHKDYEGDAPHLKARQWWEGGIYENTYKKVDGVWRMHILNYMPIWHADFESGWA 180
Qy 181 NTPHEYVPFPKVTYPEDPTGPDELIADHWLWPTHKLNPFHMKHPVTGEEMVAQRWQGDID 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NTPHEYVPFPKVTYPEDPTGPDELIADHWLWPTHKLNPFHMKHPVTGEEMVAQRWQGDID 240
Qy 241 RENARK 246
||||||
Db 241 RENARK 246
Prosecution Insights