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 .
Application Status
In response to Non-Final Office Action mailed on 10/072025, applicants’ response and amendments dated 01/07/2025 is acknowledged. Thus, amended claims 1-10, 12-13 and 17-24 are pending and are now under consideration. Rejections and/or objections not reiterated from previous office action are hereby withdrawn.
Newly submitted claims 23-24 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: New amended claims 23-24 recite non-elected sequences SEQ ID NO: 3, SEQ ID NO: 24, SEQ ID NO: 31, or SEQ ID NO: 33. Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 23-24 withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Examiner maintains the following position (see page 2 of Office-action dated 10/07/2025). Applicant's election of Group I, Claims 1-10, 12-13 and 17-22 in part and election of sequences SEQ ID NOs: 25, 26 and 27 and as species “antimicrobial peptide” (claims 1, 4 , 12 and 21-22) and “sialic acid” (claim 13) for prosecution on the merits in the reply filed on 09/15/2025 is acknowledged. Examiner would like to point out that applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, and because applicants’ 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)).The restriction requirement is still deemed proper and is therefore made FINAL.
Amended Claims 1-10, 12-13 and 17-24 are pending in this application; Group I, Claims 1-10, 12-13 and 17-22 in part and election of sequences SEQ ID NOs: 25, 26 and 27 and as species “antimicrobial peptide” (claims 1, 4, 12 and 21-22) and “sialic acid” (claim 13) reading on the elected invention is now under consideration for examination; new claims 23-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Maintained-Priority
Acknowledgment is made of applicants’ claim for foreign priority under 35 U.S.C. 119(a)-(d). This application is a 371 of PCT/EP2021/078565 filed on 10/15/2021 and claims the priority date of EPO application 20202114.3 filed on 10/15/2020; however, note the support for the elected subject-matter SEQ ID NOs: 26 and 27 is only found in 371 of PCT/EP2021/078565 filed on 10/15/2021. Therefore, the priority date for instant claims under consideration is deemed to be the filing date of 371 of PCT/EP2021/078565 filed on 10/15/2021.
Maintained-Claims Objections
Claims 9, 17 and 23-24 are objected to, as said claims recite non-elected subject-matter/SEQ ID NOs.
New-Claim Rejections: 35 USC § 112(d)
Necessitated by claim amendments
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 21 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. Examiner reiterates that the new claim 21 and instant amendments do not limit the subject-matter of claims 1-2 from which claim 21 depends from and in fact broadens the scope of claim 21. Examiner takes the position that amended claims 1-2 already includes “A polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27; b) a polynucleotide a having 90% or more sequence identity with the polynucleotide sequence of SEQ ID NO: 26 or with a polynucleotide sequence encoding SEQ ID NO: 27, and which encodes a protein having activity that transfers a soluble monosaccharide to the hydroxyl group on a threonine residues of a soluble acceptor proteins of interest; and… a protein of interest selected from the group consisting i. flagellin; ii. of Alpha-1-Antitrypsin, Interferon-beta, insulin, and an antimicrobial peptide; and iii. a flagellin fused to another soluble protein of interest” (in claim 1) and a recombinant expression vector for bacterial expression comprising the polynucleotide flmG according to claim 1” (in claim 2).
Furthermore, claim 21 recites in the alternative “recombinant expression vector according to claim 2, further comprising a polynucleotide sequence encoding a flm operon or a polynucleotide sequence encoding the soluble acceptor protein of interest…” which broadens the scope of claim 2 form which claim 21 depends from, as claim 2 includes the limitation of claim 1. Correction and clarification is required.
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 U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of pre-AIA 35 U.S.C. 112, 4th paragraph, are related to matters of form, non-compliance with pre-AIA 35 U.S.C. 112, 4th paragraph, renders the claim unpatentable just as non-compliance with other paragraphs of 35 U.S.C. 112 would. See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92, 79 USPQ2d 1583, 1589-90 (Fed. Cir. 2006) (holding a dependent claim in a patent invalid for failure to comply with pre-AIA 35 U.S.C. 112, 4th paragraph). Therefore, if a dependent claim does not comply with the requirements of 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, the dependent claim should be rejected under pre-AIA 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as unpatentable rather than objecting to the claim. See also MPEP § 608.01(n),subsection III, “Infringement Test” for dependent claims.
New-Claim Objections
Necessitated by claim amendments
Applicant is advised that should claims 21 be found allowable, claim 22 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. Claim 21 recites in the alternative “recombinant expression vector according to claim 2, further comprising a polynucleotide sequence encoding a flm operon or a polynucleotide sequence encoding the soluble acceptor protein of interest…”, and thus claim 22 does not further limit the scope of claim 2, as claims 21-22 depend from claim 2 and said claim 2 depends from claim 1 and includes the limitation of claim 1. See MPEP § 706.03(k) (see new rejection of claim 21 is rejected under 35 U.S.C. 112(d) above for claims interpretation).
New-Double Patenting rejection
Necessitated by claim amendments
Claim 22 is rejected to under 37 CFR 1.75 as being duplicate of claim 21. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k). Examiner takes the position that the scope of claim 21 and the rejected claim 22 are one and the same (also see new rejection of claim 21 rejected under 35 U.S.C. 112(d) above for claims interpretation).
New-Claim Objections
Necessitated by claim amendments
Claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom are objected to, due to the following informality: Claims 1, 6, 9 and 17 recite the phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to the nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity. Examiner suggests amending the claim to recite “…the polynucleotide composed of SEQ ID NO: 26 or the polynucleotide encoding SEQ ID NO: 27”. Appropriate correction is required. For examination purposes claims 1-10, 12-13 and 17-22 are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear.
New-Claim Rejections: 35 USC § 112(b)
Necessitated by claim amendments
(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.
Claim 1 and claims 2-10, 12-13 and 17-22 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 pre-AIA the applicant regards as the invention.
Claims 1, 6, 9 and 17 are indefinite in the recitation of phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to the nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity. Examiner suggests amending the claim to recite “…the polynucleotide composed of SEQ ID NO: 26 or the polynucleotide encoding SEQ ID NO: 27”. Appropriate correction is required. For examination purposes claims 1-10, 12-13 and 17-22 are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear. Appropriate correction is required.
Maintained-Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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, 12-13 and 17-22 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 purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus.”). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“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 . . ., reduction to drawings . . ., 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.” MPEP 2163.
Furthermore, 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
The claims recite the following broadly claimed genera:
Claims 1-10, 12-13 and 17-22 recite a genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12).
The structural elements recited in claims 1-10, 12-13 and 17-22 are not sufficient structure to form any “glycosyltransferase” and “any soluble acceptor protein” of undefined and unlimited structures having no specific structural elements of any kind and having associated activity. There in inherent unpredictability in regards to which amino acid sequences may have the associated function i.e., “glycosyltransferase” and “any soluble acceptor protein” activity and possibly fall within the claims and those amino acid sequences that do not have “glycosyltransferase” and “any soluble acceptor protein” activity. As such, claims 1-10, 12-13 and 17-22 recite a genera of biomolecules described only by a functional characteristics (i.e., being a “glycosyltransferase” and “any soluble acceptor protein”), without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.” Further, without any structural limitations for structural features that actually provide for “glycosyltransferase” and “any soluble acceptor protein” activity, claims 1-10, 12-13 and 17-22 have no defined outer bounds for the scope of “glycosyltransferase” and “any soluble acceptor protein” that fall within the scope of the claims. Due to the literal unlimited structural scope of the claims, it is not possible to provide for a representative number of species that adequately described are representative of the entire genus having no fixed structural outer boundaries. Further, such genera of altered enzymes as recited lack “a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials” and without any required structure that is sufficient for providing the recited enzyme activity, the recited genera lack 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. The claims lack adequate written description in the as-filed specification for the reasons stated.
No information, beyond the characterization of specific structures SEQ ID NOs: 25, 26 and 27 in specific cellular context gram-negative transformed host cell Caulobacter crescentus comprising the encoding polynucleotides, method of making and method of use said SEQ ID NOs: 25, 26 and 27 (see Examples 1-2, pages 22-30 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12).
The genus of polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structures and the characterization of sequences of SEQ ID NOs: 25, 26 and 27 and the encoding polynucleotides, since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Seffernick et al., (J. Bacteriol. 183(8): 2405-2410, 2001), teaches that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Broun et al., (Science 282:1315-1317, 1998), teaches that as few as four amino acid substitutions can convert an oleate 12-desaturase into a hydrolase and as few as six amino acid substitutions can transform a hydrolase to a desaturase.
(d) Specifically regarding Flagellin Modification Protein (FlmG) having a glycosyltransferase activity, the following references clearly provide evidence that there is great diversity in structure and function obtained from different microorganisms: (i) see Power et al., (FEMS Microbiol., 2003, Vol. 218: 211-222); (ii) mutations in Flagellin Modification Protein affect the glycosyltransferase activity see Johnson et al., (J. Bacteriol., 1983, Vol. 154(3): 1137-1144, entire document; and Leclerc et al., (J. Bacteriol., 1998, Vol. 180(19): 5010-5019, in IDS; entire document); and (iii) complex regulation of fljk operon expression and mutations in fljk operon affects the activity (Anderson et al., Mol. Microbiol., 2000, Vol. 38(1): 41-52).
As stated above, no information beyond the characterization of specific structures SEQ ID NOs: 25, 26 and 27 in specific cellular context gram-negative transformed host cell Caulobacter crescentus comprising the encoding polynucleotides, method of making and method of use said SEQ ID NOs: 25, 26 and 27 (see Examples 1-2, pages 22-30 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12). As the claimed genera of polypeptides and encoding polynucleotides having widely variable structures and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Applicants’ have traversed the above written-description rejection with the arguments following claim amendments (see page 15 of Applicants’ REMARKS dated 01/07/2026).
Applicants’ argue “…Without acquiescing in the propriety of this rejection, claims 1, 6, 9, and 17 are amended herein to address the rejection. Specifically, the claims are amended to recite "a polynucleotide having 90% or more sequence identity." Further, item "c)" is removed. Additionally, all mentions of "glycosyltransferase" activity are associated with sequence information and "soluble acceptor protein of interest" is further defined. Applicant submits that the ordinary artisan would understand Applicant to be in possession of claims 1-10, 12-13, and 17-20 and the written description requirement is met.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for reasons made of record in the Office-action dated 10/07/2025 and additionally for the following reasons. Applicants’ arguments are directed to a narrower interpretation of claims and not commensurate with the scope of the claims. The disclosure of the specification is still insufficient to enable the claimed method to its full scope or evidence of possession. Contrary to applicants arguments, claims as written encompass and reads on a genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12).
Furthermore, 90% sequence identity to SEQ ID NO: 26 encompasses 181 random mutations in SEQ ID NO: 26 comprising 1806 nucleotides and 90% sequence identity to SEQ ID NO: 19 encompasses 585 random mutations in SEQ ID NO: 19 comprising 5848 nucleotides. There is no support in the specification and reduction to practice of 181 random mutations in SEQ ID NO: 26 comprising 1806 nucleotides and 585 random mutations in SEQ ID NO: 19 comprising 5848 nucleotides.
As interpreted by the examiner above and the evidence provided in the cited references/scientific findings supports examiner’s position and for the following reasons: (i) random mutations affect the inter or intra molecular interactions and said interactions determine the folding, 3-D configurations and affect function; and (ii) although there are homologies between known domains of a protein i.e., conserved motifs, each of the structure/variant or any fragment thereof has its own specificity with regards to the folding, 3-D configurations and the associated activity and will not tolerate random mutations/truncations/insertions/substitution/deletions” i.e., structure correlated to function is not recited. Therefore, the scope of the instant claims are broad despite the guidance of the art and specification, the claims remain not commensurate with evidence of possession or in scope with the enabled invention. Hence, claims are reading on significant numbers of inoperative embodiments would render claims non-enabled/lack of written-description, when the specification does not clearly identify the operative embodiments or evidence of possession and undue experimentation is involved in determining those that are operative.” Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971); MPEP 2164.08(b).
Maintained-Enablement
Claims 1-10, 12-13 and 17-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for the characterization of specific structures SEQ ID NOs: 25, 26 and 27 in specific cellular context gram-negative transformed host cell Caulobacter crescentus comprising the encoding polynucleotides, method of making and method of use said SEQ ID NOs: 25, 26 and 27 (see Examples 1-2, pages 22-30 of specification). However, specification does not reasonably provide enablement for a genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claims 1-10, 12-13 and 17-22 are so broad as to encompass: a genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12). The scope of the claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polynucleotides and encoded polypeptides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to the characterization of specific structures SEQ ID NOs: 25, 26 and 27 in specific cellular context gram-negative transformed host cell Caulobacter crescentus comprising the encoding polynucleotides, method of making and method of use said SEQ ID NOs: 25, 26 and 27 (see Examples 1-2, pages 22-30 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides and encoding polynucleotides i.e., a genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12). The specification but provides no guidance with regard to the making of variants and mutants or with regard to other uses. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polynucleotides and encoded polypeptides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (for example, see Whisstock et al., Prediction of protein function from protein sequence and structure. Q Rev Biophys. 2003, Aug. 36 (3): 307-340. Review), the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to make and use the full scope of the polynucleotides and encoded polypeptides encompassed by the claims. However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.” Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971); MPEP 2164.08(b). Here, the claims read on a significant number of inoperative embodiments.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass: a genera of modified polynucleotides and encoding of polypeptides or a fragment thereof in any cellular context/gram-negative host cell i.e., polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and being selected from the group consisting… a) phrase “a polynucleotide flmG which encodes a Flagellin Modification Protein (FlmG) having glycosyltransferase activity and being selected from the group consisting of the following (a) to b) and c) or a fragment thereof encoding an active Flagellin Modification Protein (FlmG) fragment: a) a polynucleotide composed of SEQ ID NO: 26 or a polynucleotide encoding SEQ ID NO: 27”; as such, given that the claim language recites “a polynucleotide”, as the use of the indefinite article and “a” implies that there is more than one nucleic acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27 and more than one encoded polypeptide and thus makes it unclear; claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is deemed to encompass and reads on any subsequence within SEQ ID NO: 26 or SEQ ID NO: 27, as well as the full length sequence. It is suggested that “a” be replaced with “the”. The scope of the claims are unclear, as such it is unclear how homologous/identical to an amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27, a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragment of SEQ ID NO: 26 or SEQ ID NO: 27 is encompassed within the scope of the claims. Clarification and correction is required. For examination purposes, claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom is interpreted to encompass a nucleotide sequence having a homology as low as six (6) nucleotide bases to SEQ ID NO: 26 or SEQ ID NO: 27 and having any percentage homology/similarity to said sequences and thus reads on encoded polypeptides comprising “any two/dipeptide sequence encoded by a polynucleotide sequence of SEQ ID NO: 27 and having Flagellin Modification Protein (FlmG) activity and are interpreted to encompass variants and mutants of the recited sequence(s) having undefined structural similarity/homology and the scope and breadth of the claimed sequences is not clear or any functional fragment(s) of undefined and unlimited structures and having glycosyltransferase activity (as in claims 1-10, 13 and 17-22; also see claims objections, Duplicate claim rejections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation); said genus of encoding polynucleotides and the encoded polypeptides fused to any soluble acceptor protein of undefined and unlimited structures (as in claims 12), because the specification does not establish: (A) a rational and predictable scheme for modifying specific amino acid residues in any Flagellin Modification Protein (FlmG) having a glycosyltransferase activity and having no specific structural elements and an expectation of obtaining the desired biological/biochemical function; (B) a rational and predictable scheme for modifying any amino acid residue with an expectation of obtaining the desired biological/biochemical function; (C) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptide; (D) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (E) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
While as discussed above, the specification provides guidance with regard to the characterization of specific structures SEQ ID NOs: 25, 26 and 27 in specific cellular context gram-negative transformed host cell Caulobacter crescentus comprising the encoding polynucleotides, method of making and method of use said SEQ ID NOs: 25, 26 and 27 (see Examples 1-2, pages 22-30 of specification), however, the scope of claims 1-13 and 16-20 is so broad and the lack of guidance either in the specification or in the prior art, the claims remains not commensurate in scope with the enabled invention and therefore for the rejected claims, this would clearly constitute undue experimentation. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed (guided mutants). Such guidance has not been provided in the instant specification or in the prior art. The art also teaches the following regarding complexity of the structure/function relationship: The reference of Chica et al., (Curr. Opin. Biotechnol., 2005, Vol. 16: 378-384) 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 Sen et al., (Appl. Biochem. Biotechnol., 2007, Vol.143: 212-223), teaches in vitro recombination techniques such as DNA shuffling, staggered extension process (STEP), random chimera genesis on transient templates (RACHITT), iterative truncation for the creation of hybrid enzymes (ITCHY), recombined extension on truncated templates (RETT), and so on have been developed to mimic and accelerate nature's recombination strategy. However, such rational design and directed evolution techniques only provide guidance for searching and screening for the claimed polypeptide which is not guidance for making and/or using the claimed polypeptide. Additionally, knowledge is not extant in the art to assay all possible enzymatic activities, how to express all possible enzymes or how predictably assay for such activities. For example, the reference of Banerjee et al., (Bioenerg. Res. 2010, Vol. 3: 82-92), on page 84, right column, second paragraph, describe that “enzymes have critical properties besides specific activity and thermal tolerance that must be considered but which can be difficult to assay in vitro. For example, besides catalyzing a particular chemical reaction, enzymes must be efficiently translated and secreted, able to resist proteases, act cooperatively with other enzymes, and have low product and feedback inhibition. One can easily imagine that an “improved” enzyme, based on assay in isolation on a model substrate, might perform poorly in a real-world situation”.
Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including polynucleotides and encoded polypeptides with an enormous number of modifications. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of polypeptides/enzymes having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Although the claims are examined in the light of the specification, specification cannot be read into the claims, i.e., the limitations of the specification cannot be read into the claims (see MPEP 2111 R-5).
Applicants’ have traversed the above enablement rejection with the following arguments (see pages 15-16 of Applicants’ REMARKS dated 01/07/2026).
Applicants’ argue “…Without acquiescing in the propriety of this rejection, claims 1, 6, 9, and 17 are amended herein to address the rejection. Further, Applicant respectfully traverses this rejection on the ground that the present specification enables O-glycosylation in cellular hosts beyond C. crescentus. As an example, Example 2 of the present specification provides support for O- glycosylation in E. coli. Applicant submits that no undue experimentation is required by the ordinary artisan in this mature field to practice claims 1-10, 12-13, and 17-20 and the enablement requirement is met.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Applicants’ arguments filed on 01/07/2026 for the traversal of enablement rejection is on similar lines to the arguments presented for traversing the written-description, said arguments have been fully considered but they are not persuasive. Examiner continues to maintain the rejection for reasons stated on record, supporting evidence and arguments presented above in maintaining the written-description rejection also applies to enablement rejection.
New-Enablement
Necessitated by claim amendments
Claim 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Claim 8 recite specific strains i.e., the Gram-negative host is a Sinorhizobium fredii NGR234, a Sinorhizobium fredii HH103 or a Shewanella oneidensis MR-1 comprising expression vectors comprising polynucleotides and encoded polypeptides; examiner also notes that claim 8 depends from claims 7, 4 and independent claim 1 (independent claim 1 is amended); also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
It is apparent that specific strains i.e., the Gram-negative host is a Sinorhizobium fredii NGR234, a Sinorhizobium fredii HH103 or a Shewanella oneidensis MR-1 comprising expression vectors comprising polynucleotides and encoded polypeptides; examiner also notes that claim 8 depends from claims 7, 4 and amended independent claim 1; also see claims objections and 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation) is required to practice the claimed invention. As such the biological material must be readily available or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the requirements of 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, may be satisfied by a deposit of the Gram-negative host is a Sinorhizobium fredii NGR234, a Sinorhizobium fredii HH103 or a Shewanella oneidensis MR-1 comprising expression vectors comprising polynucleotides and encoded polypeptides. The specification does not disclose a repeatable method to obtain specific strains i.e., the Gram-negative host is a Sinorhizobium fredii NGR234, a Sinorhizobium fredii HH103 or a Shewanella oneidensis MR-1 comprising expression vectors comprising polynucleotides and encode polypeptides; examiner also notes that claim 8 depends from claims 7, 4 and independent claim 1 (independent claim 1 is amended); also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation), and there is no indication in the specification as to the public availability. If the deposit was made under the terms of Budapest Treaty, then a statement, affidavit or declaration by applicants’, or a statement by an attorney of record over his/her signature and registration number, or someone empowered to make such a statement, stating that the invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein. In order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, applicants’ may provide assurance of compliance by statement, affidavit or declaration, or by someone empowered to make same, or by a statement by an attorney of record over his/her signature and registration number showing that:
(a) during the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) all restrictions upon availability to the public will be irrevocably removed upon granting the patent;
(c) the deposit will be maintained in public depository for a period of 30 years, or 5 years after the last request or for the enforceable life of the patent, whichever is longer;
(d) a test of the viability of the biological material at the time of deposit (see 37 CFR 1.807); and the deposit will be replaced if it should ever become inviable.
Summary of Pending Issues
The following is a summary of issues pending in the instant application
Claim 1 and claims 2-10, 12-13 and 17-22 depending therefrom are objected to due to various informalities; for details see above.
Claim 21 is rejected under 35 U.S.C. 112(d).
Claim 22 is rejected to under 37 CFR 1.75 as being duplicate of claim 21.
Claims 1-10, 12-13 and 17-22 are rejected under 35 U.S.C. 112(a) for written-description and enablement.
Claim 8 is rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement/Biologic deposit.
Claims 23-24 withdrawn from consideration as being directed to a non-elected invention.
Conclusion
None of the claims are allowable. Claims 1-10, 12-13 and 17-22 are objected/rejected for the reasons identified in the Rejections and Summary sections of this Office Action. Applicants’ must respond to the rejections in each of the sections in this Office Action to be fully responsive for prosecution.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Regarding filing an After Final amendment, Applicants are directed to MPEP 714.13, which states:
II. ENTRY NOT A MATTER OF RIGHT
It should be kept in mind that applicant cannot, as a matter of right, amend any finally rejected claims, add new claims after a final rejection (see 37 CFR 1.116) or reinstate previously canceled claims. Except where an amendment merely cancels claims, adopts examiner suggestions, removes issues for appeal, or in some other way requires ONLY A CURSORY REVIEW by the examiner (e.g., typographical errors), compliance with the requirement of a showing under 37 CFR 1.116(b)(3) is expected in all amendments after final rejection. An affidavit or other evidence filed after a final rejection, but before or on the same date of filing an appeal, may be entered upon a showing of good and sufficient reasons why the affidavit or other evidence is necessary and was not earlier presented in compliance with 37 CFR 1.116(e). See 37 CFR 41.33 and MPEP § 1206 for information on affidavit or other evidence filed after appeal. (Examiner's emphasis) If more than a cursory review is required, Applicants are referred to CFR §1.114.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHIRAMA RAGHU whose telephone number is (571)272-4533. The examiner can normally be reached on M-F 8:30am-5pm EST.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652