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 US national phase of PCT/EP2022/082232 filed November
17, 2022, with foreign priority application EP21208979.1, filed November 18, 2021.
Applicant's Preliminary amendment filed November 20, 2024 is acknowledged. Claims 1-22 are canceled. Claims 23-39 are newly added and pending.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 26-38, and species (1) SEQ ID NO: 2; (2) arginine; (3) serine; in the reply filed on May 19, 2026 is acknowledged. Claims 23-25, 29-30, 35-37, and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 19, 2026.
Claims 26-28, 31-34, and 38 are under examination.
Claim Objections
Claim 26 is objected to because of the following informalities: line 8, needs to be changed to the “amino acid sequence of . Appropriate correction is required.
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.
Claims 26-28, 31-34, and 38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 26-28, 31-34, and 38 recite a mutated chitin oligosaccharides comprising a substitution of at least one charged amino acid present in one of the two transmembrane helices by an amino acid with the opposite charge or with no charge, wherein the said transmembrane helix comprises the amino acid regions 190-203 and 298-373 of SEQ ID NO: 2, and wherein said substitution is not an arginine which is substituted by a serine at position 349. The claims recite the charged amino acid (AA) is selected from arginine, histidine, and lysine, and the opposite charge AA is aspartic acid and glutamic acid, and the neutral (no charge) AA is serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine and tryptophan. The claims recite the arginine in position 200 and 349 of SEQ ID NO: 2 is replaced with its opposite charge or neutral charge AA. The specification discloses the transmembrane helices have an amino acid sequence identity of 30 to 100% (i.e. 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100%) to transmembrane helices of enzymes chosen from the group of: beta-polysaccharide synthase, chitin synthase, chitooligosaccharide synthase, N-acetylglucosaminyltransferase, beta-1,4-N- acetylglucosaminyltransferase, cellulose synthase, hyaluronan synthase, glycosyl transferase family 2, hyaluronic acid synthase, Nodulation protein C or NodC-like enzyme. The specification discloses the enzymes can be possibly originated from (but not solely) from the bacterial genus Rhizobium, Sinorhizobium, Cupriavidus, Burkholderia, Corallococcus, Desulfobacterium, Actinobacteria, Methylobacteria, Microvirga, Brucella, Bosea, Bradyrhizobium, Ochrobactrum, Devosia, Aminobacter, Mesorhizobium, Phyllobacterium, Agrobacterium, Allorhizobium, Neorhizobium, Shinella, Azorhizobium, Paraburkholderia and Pseudomonas. 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. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Applicant’s attention is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, "Written Description" Requirement (MPEP2163).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the specification merely gives working examples of oligomer chitin synthases from Rhizobium sp. GRH2, Sinorhizobium meliloti, and Sinorhizobium fredii with specific point mutations, and are the only species whose complete structure is disclosed. While the genus encompasses a large number of variants that have the same activity as pancreatic enzymes in kind and the genus encompasses a large number of variants that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of pancreatic enzyme variants or functional equivalents thereof.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e., other than nucleotide sequence or amino acid sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic of a mutated chitin oligosaccharide synthase is their usage to produce chitin oligosaccharides having a degree of polymerization of four, five, six and/or seven. Such a broad limitation cannot be an identifying characteristic for the claimed diverse genus of mutational variants, since by Applicant’s definition of mutated chitin oligosaccharide synthase variant or functional equivalent thereof, all members of the claimed genus will have that characteristic. Further, no other identifying characteristics of the mutated chitin oligosaccharide synthase are disclosed, only the synthases of two sequences, SEQ ID NO: 1 and 3.
In conclusion, Applicant’s disclosure of the species of ”mutated chitin oligosaccharide synthase” of the claimed broad genus is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
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 26-28, 31-34, and 38 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 26 recites “a mutated bacterial chitin oligosaccharide synthase, wherein said mutation is a substitution of at least one charged amino acid present in one or more transmembrane helices by an amino acid having the opposite charge or no charge, wherein the transmembrane helix comprises…the amino acid regions 190-203 and 298-373 of SEQ ID NO: 2, …and wherein the substitution is not an arginine substituted with a serine at amino acid position 349 of SEQ ID NO: 2.”. It is unclear if the mutated chitin oligosaccharide synthase requires 100% sequence similarity to the transmembrane helix regions recited with one or more of the specified mutations or can comprise other mutations along with the specified recited mutation(s). The specification discloses the mutated chitin oligosaccharide synthase as described above wherein said transmembrane helices have an amino acid sequence identity of 30 to 100% to transmembrane helices of enzymes chosen from the group of: beta-polysaccharide synthase, chitin synthase, chitooligosaccharide synthase, N-acetylglucosaminyl-transferase, beta-1,4-N- acetylglucosaminyltransferase, cellulose synthase, hyaluronan synthase, glycosyl transferase family 2, hyaluronic acid synthase, Nodulation protein C, or NodC-like enzyme (pg. 12, lines 1-8). Furthermore, the claim recites ‘one or more transmembrane helices’ and then recites ‘wherein the transmembrane helix comprises’ indicating 2 regions of SEQ ID NO: 1, 2 or 3. One of ordinary skill in the art would not be apprised of the metes and bounds of the claim, since the claim encompasses bacterial chitin oligosaccharide synthases other than SEQ ID NO: 2, but fails to provide an objective standard for determining which amino acid residues in those different proteins correspond to amino acid positions 190-203 and/or 298-373 of SEQ ID NO: 2 with reasonable certainty, therefore is indefinite. Claims 27-28, 31-34, and 38 are likewise rejected as being dependent on an indefinite claim.
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.
Claims 26-28, 31-34, and 38 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more.
The Supreme Court has required analysis based on a 3-part test for subject matter eligibility: Step 1: Is the claim to a process, machine, manufacture, or composition of matter? Step 2A (The Judicial Exceptions): Prong 1: Is the claim directed to a law of nature, a natural phenomenon (product of nature), or an abstract idea? Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
Claims 26-28, 31-34, and 38 recite a mutated chitin oligosaccharide synthase comprising at least one mutation in one or more amino acid regions 190-203 & 298-373 of SEQ ID NO: 1, 2 or 3, wherein the mutation is not, which is a statutory category of invention (Step 1: Yes).
Claims 26-28, 32-34, and 38 recite mutations in the chitin oligosaccharide synthase which are naturally occurring as seen in Whitman (Uniprot Accession # A0A4R3PQS6_RHISU, Submitted (MAR-2019) to the EMBL/GenBank/DDBJ databases) with a H327E substitution, Ramirez-Puebla et al. (Uniprot Accession # A0A387G0G1_9HYPH, Submitted (OCT-2018) to the EMBL/GenBank/DDBJ databases) with a H327Q substitution, and Liu et al. (NCBI Accession # AJC00901.1, Submitted (18-JUN-2014) Faculty of Agriculture and Life Sciences, Lincoln University, Ellesmere Junction Road/Springs Road, Lincoln, Christchurch, Canterbury 7647, New Zealand) with a R349P substitution. Therefore, the broad scope of the claims includes naturally occurring mutations in naturally occurring chitin synthases in relation to SEQ ID NO: 2, thus the claims recite a judicial exception in the form of a product of nature (Step 2A, Prong 1: Yes).
Claims 26-27 and 32-34 do not recite additional elements that integrate it into a practical application (Step 2A Prong 2, No), nor do the claims recite additional elements that amount to significantly more than the judicial exception (Step 2B: No.).
Claim 31 does not recite a naturally occurring chitin oligosaccharide synthase with mutations R200S & (R349D or R349E) in naturally occurring bacterial chitin synthases and would be patent eligible if rewritten in independent form. However, since this claim depends from a patent ineligible claim, claims 26-28, 31-34, and 38 are not patent eligible subject matter.
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.
Claims 26-27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Whitman (Uniprot Accession # A0A4R3PQS6_RHISU, Submitted MAR-2019 to the EMBL/GenBank/DDBJ databases).
Whitman teaches a nodulation protein C, chitooligosaccharide synthase from Rhizobium sullae (Accession # A0A4R3PQS6_RHISU) that comprises mutated transmembrane helices with amino acid regions 190-203 and 298-373 of SEQ ID NO: 2 that has substitution H327E, thus anticipates the claims (See sequence comparison below). The chitooligosaccharide synthase from R. sullae comprises the 190-203 region with 95.6% identity and the 298-373 region with 77.2% identity to SEQ ID NO: 2.
Sequence comparison of A0A4R3PQS6_RHISU & SEQ ID NO: 2
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Claims 26-27 and 32-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramirez-Puebla et al. (Uniprot Accession # A0A387G0G1_9HYPH, Submitted (OCT-2018) to the EMBL/GenBank/DDBJ databases, hereinafter “Ramirez”).
Ramirez teaches a nodulation protein C, chitooligosaccharide synthase from Rhizobium jaguaris (Accession # A0A387G0G1_9HYPH) that comprises mutated transmembrane helices with amino acid regions 190-203 and 298-373 of SEQ ID NO: 2 that has substitution H327Q, thus anticipates the claims (See sequence comparison below). The chitooligosaccharide synthase from R. sullae comprises the 190-203 region with 95.8% identity and the 298-373 region with 71.8% identity to SEQ ID NO: 2.
Sequence comparison of A0A387G0G1_9HYPH & SEQ ID NO: 2
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630
778
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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.
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.
Claims 28 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Ramirez as applied to claims 26-27 and 32-34 above, and further in view of Liu et al. (NCBI Accession # AJC00901.1, Submitted (18-JUN-2014) Faculty of Agriculture and Life Sciences, Lincoln University, Ellesmere Junction Road/Springs Road, Lincoln, Christchurch, Canterbury 7647, New Zealand, hereinafter “Liu”) and Dorfmueller et al. (THE JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, VOL.289, NO. 33, pp. 23020–23028, cited in IDS filed 9/19/2024, hereinafter “Dorfmueller”).
As cited above, Ramirez teaches a chitin oligosaccharide synthase that comprises region 190-203 & 298-373 of SEQ ID NO: 2 with a histidine (charged) to glutamine (neutral) substitution at position 327, H327Q. Ramirez does not teach the substitution of a charged amino acid, arginine, with a neutral amino acid at position 349 of SEQ ID NO: 2.
However, Liu teaches a partial N-acetylglucosaminyltransferase located in the NodC gene of Rhizobium sp. ICMP 19857 (Accession # AJC00901.1) that aligns with the 298-373 region of SEQ ID NO: 2 that comprises a R349P substitution with 83% identity (See sequence comparison below). Liu does not teach a mutation at position 349 to a neutral amino acid.
Sequence comparison of AJC00901.1 with 298-373 AA region of SEQ ID NO: 2
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However, Dorfmueller teaches structural and biochemical model of processive chitin synthesis, and discloses chitin synthases (CHS) are large, membrane integrated enzymes with multiple domains important for subcellular localization and activation; containing multiple transmembrane (TM) domains that are thought to form a transport channel for the deposition of chitin on the outer membrane, similar to cellulose synthases (title, pg. 23020, col. 2, para 2). Dorfmueller teaches yeast chitin synthase 2 (ScCHS2), which possesses several conserved sequence motifs that are essential for chitooligosaccharide synthesis, such as motifs contained in CON1 that are essential for catalytic activity, and is conserved in CHS from the bacterial NodC proteins found in Rhizobium sp. (pg. 23020, col. 2, para 3). Dorfmueller teaches a second conserved region, CON2, which is indispensable for the synthesis of long chitooligosaccharides and single mutations can affect the ability of ScCHS2 to synthesize GlcNAc oligomers longer than chitobiose (pg. 23021, col.1, para 1). In Figure 1, Dorfmueller indicates conserved NodC residues, Leu19 and Arg349, in a sequence alignment between CHS from Sinorhizobium meliloti (SmNodC) and S. cerevisiae, and the cellulose synthase BscA from Rhizobium sphaeroides, which show an arginine (positive charge) at position 349 of SmNodC, and aspartic acid (negative charge) in ScCHS2 and serine (neutral amino acid) in BscA at that same position (pg. 23031). Dorfmueller further explains, one of the key differences between SmNodC and ScCHS2/BscA is that SmNodC synthesizes only short, soluble chitooligosaccharides, up to (GlcNAc)5, whereas ScCHS2/BscA produces long, insoluble polysaccharides that are deposited in the cell wall, and discloses a previous study with chimeras of NodC enzymes from different species identified that the C terminus beyond Ile-262 regulates chitooligosaccharide product length (pg. 23026, col.1, para 2). Dorfmueller teaches the SmNodC model reveals that the C-terminal domain (Ile-262 until the C terminus) forms the product-binding site (Figs. 3A and 4A), and the product-binding site is limited by a key residue, Arg-349, which is predicted to point toward Leu-19 and defines a molecular ruler for the synthesis of chitopentaose (Fig. 5) (pg. 23026, col.1, para 2). In BcsA, longer products can be synthesized because these residues are both serines that form a proper transport channel across the membrane (Fig. 5), and SmNodC lacks additional transmembrane domains to form a transport channel across the lipid bilayer (Fig. 3A) (pg. 23026, col.1, para 2).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the chitin oligosaccharide synthase Accession # A0A387G0G1_9HYPH that comprises region 190-203 & 298-373 of instant SEQ ID NO: 2 comprising a H326Q substitution, as taught by Ramirez, and further mutate in the 298-373 region with a R349P substitution in the partial N-acetylglucosaminyltransferase located in the NodC gene of Rhizobium sp. ICMP 19857, as taught by Liu. One of ordinary skill in the art would have been motivated to mutate the Rhizobium CHS with a R349P substitution, since the charged arginine at position 349 blocks synthesis of elongated, insoluble polysaccharides that can be deposited in the cell wall, in contrast to BcsA that has a neutral amino acid (serine) at that corresponding position which can form a proper transport channel across the membrane enabling longer oligosaccharide products, as taught by Dorfmueller.
Conclusion
There is no prior art citing the claimed chitin oligosaccharide synthase comprising a R200S and (R349E or R349D) substitutions as recited in claim 31.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/JESSICA EDWARDS/
Examiner, Art Unit 1657
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