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 .
Support for the amendments is within the instant application specification.
Applicants’ amendment to the claims filed on 5/7/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-88, 106-108 are canceled.
Claims 89-105, 109-110 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 5/7/2026 is acknowledged. Examiner acknowledges Applicant’s amendment to Formula III removing the inadvertent line between functional groups R1 and R2. Examiner acknowledges Applicant’s remarks regarding the reference of Miccoy. Examiner has provided the appropriate teachings of Miccoy in the 102 rejection within the instant application.
Claims 1-88, 106-108 are cancelled.
Claims 89-105, 109-110 are pending and examined on the merits.
Priority
Acknowledgement is made of this national stage entry of PCT/EP2022/069849 of Non-provisional Application No. 18/579,664, filed on 7/15/2022, which claims foreign priority under 35 U.S.C. 119(a)-(d) to European Patent Application No. EP21186204.0, filing date 7/16/2021 and Luxembourg Patent Application No. LU500444, filing date 7/16/2021. The certified copy of European Patent Application No. EP21186204.0 has been filed in the present application on 7/15/2021.
It is noted, however, that applicant has not filed a certified copy of the English translation of Luxembourg Patent Application No. LU500444, filing date 7/16/2021 as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/16/2024, 4/24/2026, 5/6/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The hyperlinks are located on pages 17, 23, 36.
112a Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 89-105, 109-110 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claims 89-105 are drawn to a method for producing a compound comprising a structure of Formula I, II or III: Fuc-al,2-Gal-31,3-GlcNAc Fuc-al,2-Gal-31,3-GlcNAc-R Fuc-al,2-Gal-31,3-GlcNAc wherein: R1 is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide; by a cell, wherein the method comprises the steps of: i. providing a cell that is genetically engineered for producing the compound, wherein the cell expresses an alpha-1,2-fucosyltransferase, and ii. cultivating and/or incubating the cell under conditions permissive to express the compound, wherein the alpha-1,2-fucosyltransferase has galactoside alpha-1,2-fucosyltransferase activity on a galactose residue of Gal-bl,3-GlcNAc (LNB, lacto-N-biose) of the compound, and: - - comprises a polypeptide having at least 80% sequence identity to a full-length sequence of any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37, or - is a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1, 3,5,6,8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31,32,33,34,35,36 or 37. The structure of a polypeptide having at least 80% sequence identity to a full-length sequence of any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37 and a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1, 3,5,6,8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31,32,33,34,35,36 or 37 capable of accepting 20% and 30%, respectively, variability is a large number of sequences.
Claims 109-110 are drawn to a method of using a cell genetically engineered to produce a compound comprising a structure of Formula I, II or III: Fuc-al,2-Gal-31,3-GlcNAc Fuc-al,2-Gal-31,3-GlcNAc-R' Fuc-al,2-Gal-31,3-GlcNAc Formula I Formula II Formula III wherein Rl is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide; wherein the cell expresses an a-1,2-fucosyltransferase, wherein the a-1,2-fucosyltransferase has galactoside a-1,2-fucosyltransferase activity on the galactose residue of Gal-b1,3-GlcNAc (LNB) of the compound comprising a structure of Formula I, II or III and comprises a polypeptide sequence of any one of SEQ ID NO:1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21 -24, 26, 28- 36, or 37, or comprises an amino acid sequence having at least 80% sequence identity to the full-length sequence of any one of SEQ ID NO:1, 3, 5, 6,8,11- 13, 15, 19, 21 - 24, 26, 28- 36, or 37, or is a functional fragment comprising at least 70.0% of the full-length of any one of SEQ ID NO:1, 3,5,6,8, 11 - 13, 15, 19,21-24,26,28- 36, or 37, to produce the compound comprising a structure of Formula I, II or III, wherein: Rl is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide, the method comprising: cultivating the cell so as to produce the compound. The structure of a polypeptide having at least 80% sequence identity to a full-length sequence of any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37 and a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1, 3,5,6,8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31,32,33,34,35,36 or 37 capable of accepting 20% and 30%, respectively, variability is a large number of sequences.
In this case, the specification discloses the following representative species of a alpha-1,2-fucosyltransferase comprising a polypeptide are encompassed by the claims (i.e. the polypeptide of SEQ ID NO 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of polypeptides that would encompass 20% and 30% variability, respectively. The breadth of the claims encompass a large number of sequences of polypeptides with 20% and 30% variability, respectively.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to teach which combinations of amino acids out of the numerous possibilities encompass the 20% variability for the production of TMP in culture or medium from genetically modified Corynebacterium.
Accordingly, one of skill in the art would not accept the disclosure of a polypeptide SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37 as being representative of all alpha-1,2-fucosyltransferase comprising a polypeptide as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of polypeptides that comprise alpha-1,2-fucosyltransferase, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
Scope of Enablement
Claims 89-105, 109-110 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for alpha-1,2-fucosyltransferase comprising a full length amino acid sequence having at 100% amino acid identity with SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37, it does not reasonably provide enablement for all alpha-1,2-fucosyltransferase having 20% and/or 30% variation which is the same as sequences having 70% and 80%, respectively, sequence identity as said variation is comprised of a large number of sequences as encompassed by the claims. 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/or use the invention commensurate in scope with these claims.
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
(A)The breadth of the claims:
Claims 89-105 are drawn to a method for producing a compound comprising a structure of Formula I, II or III: Fuc-al,2-Gal-31,3-GlcNAc Fuc-al,2-Gal-31,3-GlcNAc-R Fuc-al,2-Gal-31,3-GlcNAc wherein: R1 is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide; by a cell, wherein the method comprises the steps of: i. providing a cell that is genetically engineered for producing the compound, wherein the cell expresses an alpha-1,2-fucosyltransferase, and ii. cultivating and/or incubating the cell under conditions permissive to express the compound, wherein the alpha-1,2-fucosyltransferase has galactoside alpha-1,2-fucosyltransferase activity on a galactose residue of Gal-bl,3-GlcNAc (LNB, lacto-N-biose) of the compound, and: - comprises a polypeptide having at least 80% sequence identity to a full-length sequence of any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37, or - is a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1, 3,5,6,8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31,32,33,34,35,36 or 37. The structure of a polypeptide having at least 80% sequence identity to a full-length sequence of any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37 and a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1, 3,5,6,8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31,32,33,34,35,36 or 37 capable of accepting 20% and 30%, respectively, variability is a large number of sequences.
Claims 109-110 are drawn to a method of using a cell genetically engineered to produce a compound comprising a structure of Formula I, II or III: Fuc-al,2-Gal-31,3-GlcNAc Fuc-al,2-Gal-31,3-GlcNAc-R' Fuc-al,2-Gal-31,3-GlcNAc Formula I Formula II Formula III wherein Rl is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide; wherein the cell expresses an a-1,2-fucosyltransferase, wherein the a-1,2-fucosyltransferase has galactoside a-1,2-fucosyltransferase activity on the galactose residue of Gal-b1,3-GlcNAc (LNB) of the compound comprising a structure of Formula I, II or III and comprises a polypeptide sequence of any one of SEQ ID NO:1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21 -24, 26, 28- 36, or 37, or comprises an amino acid sequence having at least 80% sequence identity to the full-length sequence of any one of SEQ ID NO:1, 3, 5, 6,8,11- 13, 15, 19, 21 - 24, 26, 28- 36, or 37, or is a functional fragment comprising at least 70.0% of the full-length of any one of SEQ ID NO:1, 3,5,6,8, 11 - 13, 15, 19,21-24,26,28- 36, or 37, to produce the compound comprising a structure of Formula I, II or III, wherein: Rl is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide, the method comprising: cultivating the cell so as to produce the compound. The structure of a polypeptide having at least 80% sequence identity to a full-length sequence of any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37 and a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1, 3,5,6,8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31,32,33,34,35,36 or 37 capable of accepting 20% and 30%, respectively, variability is a large number of sequences.
B) The nature of the invention; C)The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the claimed 20% variability is a large number of sequences.
It is well-known in the prior art that the amino acid sequence of a polypeptide determines the polypeptide’s functional properties. The positions within a protein's sequence where modifications can be made with a reasonable expectation of success in obtaining a polypeptide having the desired activity/utility are limited in any protein and the result of such modifications is highly 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 reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) 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]. The reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
It is well-known in the art that even a single amino acid alteration can alter the folding of a polypeptide. See, e.g., MPEP 2144.08.II.A.4.(c), which states, “[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution (“the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein.” Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990).”
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of full-length alpha-1,2-fucosyltransferase that comprises the polypeptide (i.e. alpha-1,2-fucosyltransferase that comprises SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the number of sequences that comprises the 20% and/or 30% variability of a polypeptide that comprises alpha-1,2-fucosyltransferase. Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of sequences that comprise the 20% and 30% variability of the claimed polypeptide of alpha-1,2-fucosyltransferase.
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.
Claim 93 is 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.
With regard to claim 93, the recitation of ‘…comprises a polypeptide according to any one of SEQ ID NO: 5, 6, 8 or 11, or - comprises a polypeptide having at least 80% sequence identity to the full-length sequence of any one of any one of SEQ ID NO: 5, 6, 8 or 11, or - is a functional fragment comprising at least 70.0% of the full-length of SEQ ID NO: 5, 6, 8 or 11’ is indefinite as Applicant has claimed a narrow limitation (100% sequence identity) along with broad limitations (80% sequence identity and 70% sequence identity). As recited, the sequences that have 100% identity are just one species. However, sequences that are at different sequence identities (70% and 80%) are much broader. Normally Applicant’s claim the broadest limitation first (70% sequence identity), then in the dependent claims Applicant’s claims the next broadest sequence identity (80% sequence identity) and in the next dependent claim Applicant’s claim the actual sequence identities (100% identical). In the instant case, Applicant has mixed up the sequence identities (100% identical, narrow limitation) as well as the broader genus (broader limitation) within a single claim (instant application claim 93). As such, it is unclear what is actually being claimed. Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from this phrase. Appropriate correction is suggested.
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.
Claims 89-92, 94-95, 97-105, 109-110 are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Miccoy et at (WO2015/175801A1, Date of Publication: 19 November 2015, cited on PTO-892 dated 3/11/2026) {herein Miccoy}.
The applied reference has a common Assignee and Inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Claims 89-94, 94-95, 97-105 are drawn to a method for producing a compound comprising a structure of Formula I, II or III: Fuc-al,2-Gal-31,3-GlcNAc Fuc-al,2-Gal-31,3-GlcNAc-R Fuc-al,2-Gal-31,3-GlcNAc wherein: R1 is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide; by a cell, wherein the method comprises the steps of: i. providing a cell that is genetically engineered for producing the compound, wherein the cell expresses an alpha-1,2-fucosyltransferase, and ii. cultivating and/or incubating the cell under conditions permissive to express the compound, wherein the alpha-1,2-fucosyltransferase has galactoside alpha-1,2-fucosyltransferase activity on a galactose residue of Gal-bl,3-GlcNAc (LNB, lacto-N-biose) of the compound, and: - comprises a polypeptide according to any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37, or - comprises a polypeptide having at least 80% sequence identity to a full-length sequence of any one of SEQ ID NO: 1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37, or - is a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1, 3,5,6,8, 11, 12, 13, 15, 19, 21, 22, 23, 24, 26, 28, 29, 30, 31,32,33,34,35,36 or 37.
Claims 109-110 are drawn to a method of using a cell genetically engineered to produce a compound comprising a structure of Formula I, II or III: Fuc-al,2-Gal-31,3-GlcNAc Fuc-al,2-Gal-31,3-GlcNAc-R' Fuc-al,2-Gal-31,3-GlcNAc Formula I Formula II Formula III wherein Rl is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide; wherein the cell expresses an a-1,2-fucosyltransferase, wherein the a-1,2-fucosyltransferase has galactoside a-1,2-fucosyltransferase activity on the galactose residue of Gal-b1,3-GlcNAc (LNB) of the compound comprising a structure of Formula I, II or III and comprises a polypeptide sequence of any one of SEQ ID NO:1, 3, 5, 6, 8, 11, 12, 13, 15, 19, 21 -24, 26, 28- 36, or 37, or comprises an amino acid sequence having at least 80% sequence identity to the full-length sequence of any one of SEQ ID NO:1, 3, 5, 6,8,11- 13, 15, 19, 21 - 24, 26, 28- 36, or 37, or is a functional fragment comprising at least 70.0% of the full-length of any one of SEQ ID NO:1, 3,5,6,8, 11 - 13, 15, 19,21-24,26,28- 36, or 37, to produce the compound comprising a structure of Formula I, II or III, wherein: Rl is a monosaccharide, disaccharide, oligosaccharide, protein, glycoprotein, peptide, glycopeptide, lipid or glycolipid; R2 is a monosaccharide, disaccharide or oligosaccharide, the method comprising: cultivating the cell so as to produce the compound.
With respect to claims 89-92, 94, 97-101, 103-105, 109-110, Mccoy teaches a method where a bacterium is genetically engineered to increase the efficiency and yield of fucosylated oligosaccharide products (page 4, para 2) such as 2'-fucosyllactose (2'FL), lactodifucotetraose (LDFT), lacto-N-fucopentaose I (LNF I), or lacto-N-difucohexaose I (LDFH I) (page 3, para 1). Such production of a fucosylated oligosaccharide is accomplished using an isolated nucleic acid comprising a sequence encoding a lactose-utilizing a (1,2) fucosyltransferase gene product ( e.g., polypeptide or protein), which is operably linked to one or more heterologous control sequences that direct the production of the recombinant fucosyltransferase gene product in a host production bacterium such as Escherichia coli (E. coli) (page 2, para 3). Miccoy further teaches (1,2) fucosyltransferases ( also referred to herein as α ( 1,2) FTs) utilizes lactose and catalyzes the transfer of an L-fucose sugar from a GDP-fucose donor substrate to an acceptor substrate in an alpha-1,2-linkage (page 2, para 3). The acceptor substrate is an oligosaccharide (page 2, para 3). The alpha (l ,2) fucosyltransferases are useful for expressing in host bacterium for the production of human milk oligosaccharides (HMOS), such as fucosylated oligosaccharides (page 2, para 3). Mccoy further teaches not all alpha (l ,2) fucosyltransferases can utilize lactose as an acceptor substrate (page 22, para 3). An acceptor substrate includes, a carbohydrate, an oligosaccharide, a protein or glycoprotein, a lipid or glycolipid, e.g., N-acetylglucosamine, N-acetyllactosamine, galactose, fucose, sialic acid, glucose, lactose, or any combination thereof (page 22, para 3). A preferred alpha (1,2) fucosyltransferase of the present invention utilizes GDP-fucose as a donor, and lactose is the acceptor for that donor (page 22, para 3). Mccoy further teaches said polypeptide comprises a functional fragment comprising at least 70.0% of a full-length of any one of SEQ ID NO: 1 (appendix A). Mccoy further teaches the production of lacto-N-fucopentaose I (LNF I) (page 3, para 1). Furthermore, the compounds of the invention are produced intracellularly (page 5, para 2). The approach taught by Mccoy involves the construction of microbial strains overexpressing heterologous glycosyltransferases, membrane transporters for the import of precursor sugars into the bacterial cytosol, and possessing enhanced pools of regenerating nucleotide sugars for use as biosynthetic precursors (page 19, para 2). Said method also includes the purification of the fucosylated oligosaccharide produced by the genetically engineered bacterium by separating the desired fucosylated oligosaccharide ( e.g., 2' -FL) from contaminants in a bacterial cell lysate or bacterial cell culture supernatant of the bacterium (page 11, para 2).
It is noted that Applicant has recited characteristics of the enzyme that do not require any active steps. As such, absent evidence otherwise, it is the Examiner’s position that since Mccoy teaches an alpha (1,2) fucosyltransferase comprised of a polypeptide with at least 70% sequence homology to the instant application SEQ ID NO: 1 (appendix A) that can utilize galactose as substrate, then said polypeptide necessarily have galactoside alpha-1,2-fucosyltransferase activity on a galactose residue of Gal-bl,3-GlcNAc, as recited in the instant application claims 89, 109; have additional galactoside alpha-1,2-fucosyltransferase activity on the galactose residue at a non-reducing end of Gal-bl,3-GlcNAc-bl,3-Gal-bl,4-Glc (LNT, lacto-N- tetraose), as recited in the instant application claim 91; have no additional galactoside alpha-1,2-fucosyltransferase activity on lactose or has additional galactoside alpha-1,2-fucosyltransferase activity on lactose, which is lower than its additional galactoside alpha-1,2-fucosyltransferase activity on the galactose residue at the non-reducing end of LNT, as recited in the instant application claim 92; have additional galactoside alpha-1,2-fucosyltransferase activity on lactose that is higher than its additional galactoside alpha-1,2-fucosyltransferase activity on the galactose residue at the non-reducing end of LNT, as recited in the instant application claim 95; have no galactoside alpha-1,2-fucosyltransferase activity on the galactose residue at a non-reducing end of LNT, as recited in the instant application claim 94. Since the Office does not have the facilities for examining and comparing Applicants’ enzyme with the enzyme of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the enzyme of the prior art does not possess the same material structural and functional characteristics of the claimed enzyme). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 102, since Mccoy teaches the method for producing a compound comprising a structure of Formula I, II or III: Fuc-al,2-Gal-31,3-GlcNAc Fuc-al,2-Gal-31,3-GlcNAc-R Fuc-al,2-Gal-31,3-GlcNAc, then the cell of the invention would inherently produce a mixture of (i) charged disaccharides/oligosaccharides or (ii) neutral disaccharides/oligosaccharides or (iii) charged disaccharides/oligosaccharides and neutral disaccharides/oligosaccharides, wherein the mixture comprises at least one compound comprising a structure of Formula I, II or III, wherein R1, when present, is a monosaccharide, a disaccharide or an oligosaccharide. Since the Office does not have the facilities for examining and comparing Applicants’ claimed cellular products with the cellular products of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the cellular contents of the prior art does not possess the same material structural and functional characteristics of the claimed cellular products). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.. .
For the reasons stated herein, the teachings of Miccoy anticipate claims 89-92, 94-95, 97-105, 109-110.
Conclusion
Status of the claims
Claims 1-88, 106-108 are cancelled.
Claims 89-105, 109-110 are pending and examined on the merits.
Claims 89-105, 109-110 are rejected.
No claims are in condition for allowance.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Instant Application SEQ ID NO: 1 vs Mccoy et al SEQ ID NO: 41 (STIC search .rag)
Query Match 71.2%; Score 1007; Length 267;
Best Local Similarity 68.5%;
Matches 183; Conservative 36; Mismatches 48; Indels 0; Gaps 0;
Qy 1 MIIVRILGGLGNQMFQYAFAKSLQQKGFEVQIDISKFKTYKLHGGYHLDTYNIDLETANS 60
|::|||||||||||||||:|||| :||:||||||||||:|||||||||| : ||||||||
Db 1 MVVVRILGGLGNQMFQYAYAKSLAEKGYEVQIDISKFKSYKLHGGYHLDKFRIDLETANS 60
Qy 61 FDTFLALIKLKKNVKEKSLLFDENMLKLSGNEFVKGYFQTEKYFSTIRGILLQQFTIKTE 120
||: | ||| :|| :||| :::||:: | |:||||| |:||| || ||: || || |
Db 61 SSAFLSKIGLKKTIKEPNLLFHKDLLKVNNNAFIKGYFQAEQYFSDIREILINQFKIKKE 120
Qy 121 LSDSTKKYSKAIHQHKNSCSLHIRRGDYITDKKANSVHGTCDLNYYASAIKLINEKFENT 180
|: || | | :||||:||||||:||||| |||||||:||:|||: |::: |
Db 121 LAKSTLAIKNQIELLKTTCSLHVRRGDYISDKKANKVHGTCDLDYYSSAIEHISKQNSNV 180
Qy 181 HFFVFSDDIIWTKENLQLENATYIDHKTIPHEDMFLMSLCKHNITANSSFSWWGAWLNQH 240
||||||||| | |:|| : ||||||| ||||||:||:|| ||||||||||||||||||:
Db 181 HFFVFSDDIAWVKDNLNITNATYIDHNVIPHEDMYLMTLCNHNITANSSFSWWGAWLNQN 240
Qy 241 KNKTVIAPKKWFVSQENEVASKNWIQL 267
:| ||||| ||| :||||| |:|| |
Db 241 PDKIVIAPKNWFVDKENEVACKSWITL 267
Prosecution Insights