DETAILED ACTION
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 .
Applicant’s cancellation of claims 6-9, in the paper of 4/8/2025, is acknowledged. Claims 1-5, 10-15 are still at issue and are present for examination.
Election/Restrictions
Applicant's election with traverse of the invention of Group 1, claims 1-8 and 10-15, to an enzyme for catalyzing production of lacto-N-triose II, in the paper of 6/18/2026, is acknowledged. Applicant's election with traverse of Species Group 1 species: SEQ ID NO:2 and Species Group 2 species: SEQ ID NO:4, in the paper of 6/18/2026, is acknowledged.
Applicants traverse the restriction and species election on the basis that all claims and species is sufficiently related that a thorough search for the subject matter of any one Group of claim or species would encompass a search for the subject matter of the remaining claims and species and that this search could be made without a serious burden.
Applicants complete traversal is acknowledged and has been carefully considered, however, is found nonpersuasive for the reasons previously made of record.
Applicant is remined that the basis of the restriction requirement and species election requirement is unity of invention. As stated in the previous office action, the groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: Where a group of inventions is claimed in an application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression "special technical features" shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art. In the instant case, Genbank Accession No. AAC44084.1 discloses an enzyme for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase. Thus, the shared technical feature is not special and unity of invention is lacking.
Further while the groups may be related they are not so related that a search for one group would suffice for the other groups. Further if restriction was not made it would result in an additional search and examination burden on the examiner based upon the different databases, search terms and search rationale required for the different groups.
Claims 3, 5, 9,16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Applicants filing of information disclosure statements on 5/16/2024 are acknowledged and have been considered.
Specification
The disclosure is objected to because of the following informalities:
Applicants specification is objected to because applicants specification comprises Nucleotide and/or Amino Acids Disclosures Requiring a "Sequence Listing".
Applicants attention is directed to 37 CFR 1.821(a) which presents a definition for "nucleotide and/or amino acid sequences." This definition sets forth limits, in terms of numbers of amino acids and/or numbers of nucleotides, at or above which compliance with the sequence rules is required. Nucleotide and/or amino acid sequences as used in 37 CFR 1.821 through 37 CFR 1.825 are interpreted to mean an unbranched sequence of four or more amino acids or an unbranched sequence of ten or more nucleotides.
Specifically applicants specification at Table 1 page 12, lists 6 nucleotide sequences which require a sequence identifier and are to be included in applicants sequence listing as per 37 CFR 1.821 through 37 CFR 1.825.
Appropriate correction is required.
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 1, 2, 4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Claims 1, 2, 4 are directed an enzyme for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase, that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., 106 USPQ2d 1972 (June 13, 2013). WP_000199766.1 which discloses and naturally occurring enzyme from Helicobacter pylori having 100% sequence identity to instant SEQ ID NO:2, evidence that an enzyme for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase comprising the amino acid sequence of SEQ ID NO:2 is a naturally occurring method and is thus not patent eligible.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 11, 12 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 2 is indefinite in the recitation “possessing the activity to catalyze the production of LNTII” is confusing and unclear as it is unclear what this “activity” is. In the interest of advancing prosecution the recitation is interpreted as “catalyzes the production of LNTII”.
Claim 11 (claim 12 dependent on) is indefinite in the recitation “wherein the recombinant yeast with yeast as a host cell, wherein the yeast is selected from…” is confusing and unclear. In the interest of advancing prosecution “wherein the recombinant yeast is selected from…”.
Appropriate correction and/or comment 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.
Claim(s) 1, 2, 4, 6-8, 10-15 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.
Claim(s) 1, 2, 4, 6-8, 10-15 are directed to all possible enzymes for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is acetylglucosaminyl transferase comprising an amino acid sequence with as little as 70% sequence identity to SEQ ID NO:2 and recombinant yeast comprising said enzyme. The specification, however, only provides the representative species of that enzyme for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase comprising the amino acid sequence SEQ ID NO:2, encompassed by these claims. There is no disclosure of any particular structure to function/activity relationship in the disclosed species. The specification also fails to describe additional representative species of enzymes for catalyzing the production of lacto-N-triose II (LNTII) by identifying structural characteristics or properties, for which no predictability of structure is apparent.
Regarding the level of skill and knowledge in the art of amino acid mutation, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with amino acid mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
Given this lack of additional representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim(s) 1, 2, 4, 6-8, 10-15 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for that enzymes for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase comprising the amino acid sequence of SEQ ID NO:2 and recombinant yeast comprising said enzyme, does not reasonably provide enablement for all possible enzymes for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase comprising an amino acid sequence with as little as 70% sequence identity to SEQ ID NO:2 and recombinant yeast comprising said enzyme. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and 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).
Claim(s) 1-20 are so broad as to encompass all possible enzymes for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is acetylglucosaminyl transferase comprising an amino acid sequence with as little as 70% sequence identity to SEQ ID NO:2 and recombinant yeast comprising said enzyme. The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of enzymes for catalyzing the production of lacto-N-triose II (LNTII), and variants broadly encompassed by the claims. The claims rejected under this section of U.S.C. 112, first paragraph, place minimal structural limits on the enzymes for catalyzing the production of lacto-N-triose II (LNTII), encompassed by the claims. Since the amino acid sequence of a protein 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, 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 proteins' structure relates to its function. However, in this case the disclosure is limited to that enzyme for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is acetylglucosaminyl transferase comprising the amino acid sequence of SEQ ID NO:2 and recombinant yeast comprising said enzyme.
While recombinant and mutagenesis techniques are known, it is not routine in the art to screen for multiple substitutions or multiple modifications, as encompassed by the instant claims, and the 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 modify 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 any possible enzymes for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase comprising an amino acid sequence with as little as 70% sequence identity to SEQ ID NO:2 and recombinant yeast comprising said enzyme, because the specification does not establish: (A) regions of the enzymes for catalyzing the production of lacto-N-triose II (LNTII) which may be modified effecting the acetylglucosaminyl transferase activity; (B) the general tolerance of acetylglucosaminyl transferase enzymes to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue of an acetylglucosaminyl transferase enzyme with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. Because of this lack of guidance, the extended experimentation that would be required to determine which substitutions would be acceptable to retain the required lipase activities and the fact that the relationship between the sequence of a peptide and its tertiary structure (i.e. its activity) are not well understood and are not predictable (e.g., see Ngo et al. in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz et al. (ed.), Birkhauser, Boston, MA, pp. 433 and 492-495; Franceus et al., J. Ind. Microbiol. Biotechnol. Vol 44, pp 687-695, 2017), it would require undue experimentation for one skilled in the art to arrive at the majority of those enzymes for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase comprising an amino acid sequene with as little as 70% sequence identity to SEQ ID NO:2 and recombinant yeast comprising said enzyme of the claimed genus.
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 any enzyme for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase comprising an amino acid sequene with as little as 70% sequence identity to SEQ ID NO:2 and recombinant yeast comprising said enzyme. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of those enzymes for catalyzing the production of lacto-N-triose II (LNTII) 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).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WP_000199766.1.
WP_000199766.1 discloses a glucosyltransferase family 8 protein derived from Helicobacter pylori having 100% sequence identity to instant SEQ ID NO:2. Thus WP_000199766.1 anticipates the claimed enzyme for catalyzing the production of lacto-N-triose II (LNTII), classified according to the Carbohydrate-Active Enzymes (CAZy) database as belonging to the glycoside hydrolase family 28, wherein the enzyme is a acetylglucosaminyl transferase and comprises the amino acid sequence of SEQ ID NO:2.
Thus claim(s) 1, 2, 4 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WP_000199766.1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 2, 4, 6, 7, 8, 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over WP_000199766.1., Koo et al., (US 2014/0178933), Uniprot Accession No. A0A7D5U485, Dec 2020 and Kapitonov and Yu, (Glycobiology Vol 9, No. 10, pp 961-978, 1999).
WP_000199766.1 discloses a glucosyltransferase family 8 protein derived from Helicobacter pylori having 100% sequence identity to instant SEQ ID NO:2.
Koo et al., US 2014/0178933 disclose an expression vector which is capable of overexpressing a protein of interest in a host cell, a host cell comprising the expression vector, and a method of producing a protein of interest are provided. Koo et al. disclose an expression vector, comprising: a replication origin permitting replication of the vector in a Kluyveromyces cell; a promoter functional in Kluyveromyces selected from the group consisting of CYC promoter, TEF promoter, GPD promoter and ADH promoter; and a terminator. Koo et al. teach the use of the above expression vector to express proteins of interest, including amylases, xylanases, cellulases, hemicellulases, esterases, peroxidases, catalases, glucose oxidases, phytases, pectinases, glucosidases, isomerases, transferases and galactosidases, in Kluyveromyces marxianus cells, followed by isolating the protein of interest. Koo et al. further teach that the Kluyveromyces host cells comprise a marker gene which comprises a nucleotide sequence encoding a b-galactosidase. The encoded b-galactosidase comprises an amino acid sequence which has at least 50% sequence identity to instant SEQ ID NO:4 as evidenced by Uniprot Accession No. A0A7D5U485, Dec 2020.
Kapitonov and Yu, (Glycobiology Vol 9, No. 10, pp 961-978, 1999) review studies of glycosyltransferases, discussing conserved domains of glycosyltransferases and how these are related to a potential mechanism for catalytic reaction.
One of skill in the art before the effective filing date would have been motivated to express the glucosyltransferase of SEQ ID NO:2, taught by WP_000199766.1, the in a Kluyveromyces cell using the expression vector and methods taught by Koo et al. followed by isolating the expressed glucosyltransferase of SEQ ID NO:2 for its use in studying glycoconjugate metabolism such as myelin formation as taught by Kapitonov and Yu. The expectation of success is high based upon the high level of skill in the art of recombinant protein expression as exemplified by Koo et al.
Thus, claim(s) 1, 2, 4, 6, 7, 8, 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over WP_000199766.1., Koo et al., US 2014/0178933 and Kapitonov and Yu, (Glycobiology Vol 9, No. 10, pp 961-978, 1999)
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
8/26/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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