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 .
Application Status
This action is written in response to applicant’s correspondence received 17 July 2026. Claims 1-9, 11-15, 21-22, and 24-25 are currently pending. Accordingly, claims 1-9, 11-15, 21-22, and 24-25 are examined herein. The restriction requirement mailed 11 June 2024 has been withdrawn.
Any rejection or objection not reiterated herein has been overcome by amendment.
Applicant' s arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 4, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856) and Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015).
Regarding claims 1-2 and 21, Baumgärtner is drawn towards a review concerned with the synthesis of fucosylated lacto-N-tetraose in E. coli (Abstract). Baumgärtner teaches the use of a recombinant E. coli strain comprising recombinant nucleic acids (i.e., a recombinant microorganism) that are chromosomally integrated (i.e., genome-integrated), termed “LJ-AYFO14-cat”, that comprises a chromosomally integrated β1,3-N-acetylglucosaminyltransferase (i.e., termed “Lgta”), a β1,3-galactosyltransferase (i.e., termed WbgO”), and a bacterial α1,4-fucosyltransferase (i.e., termed “FucT”) (pg. 6801; see Table 2) that enables the whole-cell biotransformation of lactose to lacto-N-tetraose (i.e., termed “LNT”) (Abstract; see Figure 1 of Baumgärtner below). Baumgärtner teaches that via the additional expression of a recombinant GDP-l-fucose salvage pathway (i.e., a functional GDP-fucose biosynthetic pathway termed “GDP-Fuc” in Figure 1 of Baumgärtner below) together with the FucT, LNT is further converted into a fucosylated compound (i.e., termed “Fuc.LNT”) (Abstract; see Figure 1 of Baumgärtner below).
PNG
media_image1.png
368
358
media_image1.png
Greyscale
Baumgärtner teaches that previously studies have taught that the pathway of fucosylation of LNT can be carried out, in vitro, with an α1,3/4-fucosyltransferase and that the fucosylation results in the production of LNFP-V (pg. 6800). Baumgärtner teaches that “thus, for the in vivo synthesis of fucosylated LNT with a Lewis A structure, an α1,3/4- or α1,4-fucosyltransferase activity is needed” (pg. 6800).
Although Baumgärtner teaches using α1,3/4-fucosyltransferase for the production of LNFP-V and the genomic integration of an α1,4-fucosyltransferase, the reference does not teach that the coding sequence for the α1,3/4-fucosyltransferase was genomically integrated (Claim 1). Baumgärtner does not teach or suggest the use of a polypeptide having α1,3/4-fucosyl transferase activity that comprises 100% identity to the claimed SEQ ID NO: 1 (Claims 1-2). Baumgärtner does not teach or suggest the use of a polypeptide having α1,3/4-fucosyl transferase activity that consists of the claimed SEQ ID NO: 1 (Claim 21).
Yu is drawn towards a study concerned with how an H. pylori α1,3/4-fucosyl transferase expressed in an E. coli cell (i.e., a recombinant microorganism) allowed for the high-yield production of Lewis antigens derived from lactose (Abstract). Yu teaches that a vector (i.e., a nucleic acid sequence) encoding the H. pylori α1,3/4-fucosyl transferase was able to be successfully expressed within the E. coli strain (pg. 2).
Thus, Yu teaches that a heterologous H. pylori α1,3/4-fucosyl transferase was able to be expressed within an E. coli strain.
Ma is drawn towards a study concerned with a fucosyltransferase from H. pylori that has both α1,3 and α4 activities, and teaches the use of an bacterial H. pylori α1,3/4-fucosyl transferase that has 100% identity to the claimed SEQ ID NO: 1 (pg. 36848; see previously attached sequence alignment).
Thus, Ma teaches that the claimed SEQ ID NO: 1 was a known H. pylori α1,3/4-fucosyl transferase sequence.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have genomically integrated an α1,3/4-fucosyl transferase gene in the recombinant microorganism of Baumgärtner because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. Because Baumgärtner teaches that nucleic acids encoding heterologous nucleic acid sequences encoding fucosyltransferases could be integrated into a recombinant microorganism, and Yu teaches the successful use of a heterologous nucleic acid sequence encoding an α1,3/4-fucosyl transferase for a similar purpose in a similar cell, namely the fucosylation of LNT in recombinant E. coli cells, then one would have a reasonable expectation of success in genomically integrating the nucleic acid sequence encoding the α1,3/4-fucosyl transferase of Yu in order to arrive at a recombinant microorganism that could genomically express α1,3/4-fucosyl transferases. And because Baumgärtner teaches that the activity of an α1,3/4-fucosyl transferase is required for the production of LNFP-V, then one would have been motivated to genomically integrate the claimed α1,3/4-fucosyl transferase in the recombinant microorganism of Baumgärtner in order to produce LNFP-V.
It is noted that the claims require an α1,3/4-fucosyl transferase that comprises at least 90% identity to the claimed SEQ ID NO: 1. However, it would have been obvious to have used the α1,3/4-fucosyl transferase consisting of the claimed SEQ ID NO: 1, described by Ma, because it would have amounted to simple substitution of one known α1,3/4-fucosyl transferase for another. Because the two α1,3/4-fucosyl transferases are drawn towards the same enzyme from the same organism (i.e., the enzymes share a common function), then it would have been predictable to have used the claimed SEQ ID NO: 1 as the α1,3/4-fucosyl transferase in order to generate a recombinant microorganism that is capable of producing LNFP-V as discussed by Baumgartner.
Regarding claim 4, Baumgärtner teaches that the recombinant microorganism further comprises a functional GDP-fucose biosynthetic pathway termed “GDP-Fuc” (see Figure 1 of Baumgärtner above) (Abstract).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856) and Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015) as applied to claims 1-2, 4, and 21 above, and further in view of Peng (Genomics 91.1 (2008): 78-87).
Regarding claim 5, Baumgärtner in view of Ma and Yu renders obvious claims 1-2, 4, and 21 as described above.
Baumgärtner further teaches that the β-1,3-N-acetylglucosaminyl transferase can be encoded by a lgtA gene of Neisseria meningitidis (pg. 6800).
Baumgärtner in view of Ma and Yu does not teach or suggest that the Neisseria meningitidis is Neisseria meningitidis 053442 (Claim 5).
Peng is drawn to a study concerned with characterization of the genome of Neisseria meningitidis 053442 (Abstract). Peng teaches that Neisseria meningitidis 053442 was a well-known Neisseria meningitidis clone that has had its genome fully characterized (Abstract). Peng teaches that Neisseria meningitidis 053442 was known to comprise an lgtA gene that encoded an lgtA protein (pg. 83).
Thus, Peng teaches that Neisseria meningitidis 053442 comprises a known lgtA gene that functions identically to the lgtA gene of Neisseria meningitidis described by Baumgärtner.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the claimed lgtA gene of Neisseria meningitidis 053442 because it would have amounted to a simple substitution of one known Neisseria meningitidis lgtA gene for another. Since Baumgärtner teaches using an lgtA gene from Neisseria meningitidis for the conversion of lactose of LNT II (see Figure 1 above), it would have been predictable to have similarly used an lgtA gene from a specific clone of Neisseria meningitidis for the same reason.
Claim(s) 6-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856) and Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015) as applied to claims 1-2, 4, and 21 above, and further in view of Weisenborn (Journal of Biological Chemistry 267.9 (1992): 6122-6131) and “L19201.1” (GenBank Accession No. L19201.1; published 25 July 2016).
Regarding claims 6-7, the claims are drawn towards a variant of a glp promoter set forth in SEQ ID NO: 5. The instant specification teaches that the term “variant” encompasses variations of nucleic acids, so long as they are at least 70%-99.9% similar to the claimed nucleic acid (Instant specification; pg. 10). Thus, the claims are interpreted as requiring a glp promoter variant that has at least 70% identity to the claimed SEQ ID NO: 5.
Baumgärtner in view of Ma and Yu renders obvious claims 1-2, 4, and 21 as described above.
Baumgärtner further teaches that the lgtA gene was placed under the control of a heterologous Ptac-promoter (pg. 6800) and the fucosyltransferase placed under the control of a rhamnose-inducible promoter (pg. 6801).
Thus, Baumgärtner teaches that the heterologous nucleic acid sequences could be placed under control of heterologous promoter sequences.
Baumgärtner in view of Ma and Yu does not teach or suggest that the heterologous nucleic acid sequences are placed under the control of a glp promoter variant set forth in SEQ ID NO: 5 (Claims 6-7).
Weisenborn is drawn to a study concerned with the structure and regulation of the glpFK operon encoding glycerol diffusion facilitator and glycerol kinase in E. coli (Abstract). Weisenborn teaches the use of different recombinant plasmids glp promoters, selected from glpABC, glpTQ, glpD, and glpFK, that could be present within a plasmid and fused to a heterologous nucleic acid sequence encoding a β-Galactosidase such that the β-Galactosidase could be successfully expressed within the E. coli cell (pg. 6123, 6127-6128; see Table V). Weisenborn teaches that the glpFK promoter demonstrated the highest level of expression of the heterologous nucleic acid sequence encoding the β-Galactosidase (pg. 6127; see Table V).
Thus, Weisenborn teaches that utilizing glpFK promoters to express heterologous nucleic acid sequences in E. coli was beneficial due to their high expression.
L19201.1 is drawn towards a GenBank accession that characterizes minutes 87.2-89.2 of an E. coli chromosomal region (pg. 5). L19201.1 teaches that base pairs 79731-80023 comprises a glpFK promoter sequence that is 95% identical to, and complementary to, the claimed SEQ ID NO: 5 (i.e., a variant of SEQ ID NO: 5) (see pg. 5-7 of previously attached sequence alignment).
Thus, L19201.1 teaches that the claimed variant of SEQ ID NO: 5 was a known glpFK promoter.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed variant of a glp promoter set forth in SEQ ID NO: 5 because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. Because Weisenborn teaches using glpFK promoters for a similar purpose as Baumgärtner, namely the expression of heterologous nucleic acids in E. coli, then one would have had a reasonable expectation of success in using the promoter for the expression of the heterologous nucleic acids of Baumgärtner. And because Weisenborn teaches that the glpFK promoter showed the highest expression of the heterologous nucleic acids, one would have been motivated to do so.
It is noted that the claims require a variant of a glp promoter that is at least 70% identical to the claimed SEQ ID NO: 5. However, it would have been obvious to have used the glpFK promoter comprising 95% identity to the claimed SEQ ID NO: 5, described by L19201.1, because it would have amounted to simple substitution of one known glpFK promoter for another. Because the two glpFK promoters are drawn towards the same promoter from the same organism, then it would have been predictable to have used the claimed variant of SEQ ID NO: 5 as the heterologous promoter.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856) and Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015) as applied to claims 1-2, 4, and 21 above, and further in view of Wood (Journal of microbiological methods 133 (2017): 46-51).
Regarding claim 8, Baumgärtner in view of Ma and Yu renders obvious claims 1-2, 4, and 21 as described above.
Baumgärtner in view of Ma and Yu does not teach or suggest that the heterologous nucleic acid sequence is integrated in the genome of the microorganism in a single copy (Claim 8).
Wood is drawn towards a study concerned with methods for enhancing yields of single-copy number plasmid DNA from E. coli cells (Abstract). Wood teaches that molecular biologists routinely use single-copy number plasmids in order to express heterologous proteins in E. coli (pg. 46). Wood teaches that having reduced copy number plasmids can decrease basal, or uninduced, intracellular levels of an expressed protein, which is advantageous because some foreign proteins are toxic even at very low levels and therefore can inhibit growth of the E. coli cells (pg. 46). Wood teaches that utilizing TB as the culture medium for E. coli cells transformed with single-copy number plasmids consistently generated the greatest amount of plasmid DNA (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the recombinant microorganism rendered obvious above such that each heterologous nucleic acid sequence is integrated into the microorganism in a single copy because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. Because Wood teaches that a single copy of a nucleic acid encoding a recombinant protein could be utilized for a similar purpose as Baumgärtner, namely the expression of heterologous nucleic acids in E. coli, then one would have had a reasonable expectation of success in utilizing a single copy of the heterologous nucleic acids of Baumgärtner in order to encode the heterologous proteins. And because Wood teaches that using a single copy of a nucleic acid allows for reduced toxicity in the host cell, one would have been motivated to do so.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856) and Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015) as applied to claims 1-2, 4, and 21 above, and further in view of Huang (Metabolic engineering 41 (2017): 23-38) and Laffend (Biotechnology and bioengineering 43.5 (1994): 399-410).
Regarding claim 11, Baumgärtner in view of Ma and Yu renders obvious claims 1-2, 4, and 21 as described above.
Baumgärtner in view of Ma and Yu does not teach or suggest that the GDP- fucose biosynthetic pathway comprises recombinant manA, manB, manC, gmd and wcaG genes that are expressed under the control of a lac promoter (Claim 11).
Huang is drawn to a study concerned with metabolic engineering of E. coli for the production of 2’-fucosyllactose and 3-fucosyllactose (Abstract). Huang teaches that manA, manB, manC, gmd and wcaG play important roles in the GDP-fucose biosynthetic pathway (pg. 24; see Fig. 1). Huang teaches the use of multiple recombinant plasmids wherein various transferases are under the control of the same operon as manA, manB, manC, gmd and wcaG (see pg. 1 and Table T3 of Supplementary Methods).
Laffend is drawn to a study concerned with induction of protein synthesis from lac-based promoters has been developed and incorporated into the single-cell model of Escherichia coli with transcriptional and translational modifications (Abstract). Laffend teaches that the use of lac promoters for protein expression in E. coli are well known in the art (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the recombinant microorganism rendered obvious above such that the GDP- fucose biosynthetic pathway comprises recombinant manA, manB, manC, gmd and wcaG genes that are expressed under the control of a lac promoter because it would have merely amounted to simple substitution of one known GDP-fucose biosynthetic pathway for another. Because Huang teaches that GDP-fucose biosynthetic pathways comprising the claimed genes can be utilized for a similar purpose as Baumgärtner, namely the generation of fucosylated compounds in recombinant E. coli cells, then it would have been predictable to utilize the GDP-fucose biosynthetic pathway of Huang in order to generate fucosylated LNT within the recombinant microorganism of Baumgärtner.
It is noted that the claims require that the pathway is placed under control of a lac promoter. However, it would have been obvious to have used the lac promoter, described by Laffend, because it would have amounted to simple substitution of one known promoter for another. Because the two promoters are drawn towards promoters that can express proteins in E. coli cells, then it would have been predictable to have used the claimed lac promoter as the heterologous promoter controlling the biosynthetic pathway.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856), Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015), Huang (Metabolic engineering 41 (2017): 23-38), and Laffend (Biotechnology and bioengineering 43.5 (1994): 399-410) as applied to claim 11 above, and further in view of Weisenborn (Journal of Biological Chemistry 267.9 (1992): 6122-6131) .
Regarding claim 12, Baumgärtner in view of Ma, Huang, and Laffend, renders obvious claims 11 as described above.
Baumgärtner in view of Ma, Huang, and Laffend does not teach or suggest that additional copies of the genes involved in the GDP-fucose biosynthetic pathway are integrated in the genome of the microorganism under control of a glp promoter (Claim 12).
However, the applicable teachings and obviousness rationale of utilizing a glp promoter is discussed above as applied to claims 6-7 in view of Weisenborn and L19201.1.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed utilization of a glp promoter because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. Because Weisenborn teaches using glpFK promoters for a similar purpose as Baumgärtner, namely the expression of heterologous nucleic acids in E. coli, then one would have had a reasonable expectation of success in using the promoter for the expression of the heterologous nucleic acids of Baumgärtner. And because Weisenborn teaches that the glpFK promoter showed the highest expression of the heterologous nucleic acids, one would have been motivated to do so in order to drive the expression of the genome integrated heterologous nucleic acids in the recombinant microorganism with a highly active promoter.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856) and Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015) as applied to claims 1-2, 4, and 21 above, further in view of Zeuner (Enzyme and Microbial Technology 115 (August 2018): 37-44).
Regarding claim 14, Baumgärtner in view of Ma and Yu renders obvious claims 1-2, 4, and 21 as described above.
Baumgärtner further teaches that the recombinant microorganism was cultured in the presence of lactose (pg. 6804).
Baumgärtner in view of Ma and Yu does not teach or suggest a method comprising separating LNFP-V from a culture medium comprising the recombinant microorganism of claim 1 and lactose following its production (Claim 14).
Zeuner is drawn towards a study concerned with the engineering of an α3/4-fucosidase for improved synthesis of human milk oligosaccharides in E. coli cells (Abstract). Zeuner teaches that small amounts of LNFP V generated by the transfucosylation of LNT via α-1,3/4-fucosidases from Bifidobacterium bifidum and Clostridium perfringens present within an E. coli cell could be separated and detected (pg. 43).
Thus, Zeuner teaches that LNFP V generated from recombinant E. coli cells could be separated from the recombinant microorganism.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have separated the LNFP-V from the recombinant microorganism of claim 1 because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. Because Zeuner teaches that E. coli cells can be utilized for a similar purpose as Baumgärtner, namely the generation of fucosylated compounds derived from LNT, then one would have had a reasonable expectation of success in separating the LNFP V generated by the recombinant microorganism. And because Huang teaches that LNFP V was able to be isolated from recombinant E. coli cells following its generation, one would have been motivated to do so in order to validate the production of the LNFP V.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baumgärtner (Bioorganic & medicinal chemistry 23.21 (2015): 6799-6806) in view of Ma (Journal of Biological Chemistry 280.44 (2005): 36848-36856), Yu ("H. pylori α1–3/4-fucosyltransferase (Hp3/4FT)-catalyzed one-pot multienzyme (OPME) synthesis of Lewis antigens and human milk fucosides." Chemical communications 53.80 (2017): 11012-11015), Huang (Metabolic engineering 41 (2017): 23-38), Laffend (Biotechnology and bioengineering 43.5 (1994): 399-410), and Weisenborn (Journal of Biological Chemistry 267.9 (1992): 6122-6131) as applied to claim 12 above, and further in view of “L19201.1” (GenBank Accession No. L19201.1; published 25 July 2016).
Regarding claim 23, Baumgärtner in view of Ma, Huang, Laffend, and Weisenborn renders obvious claim 12 as described above.
Baumgärtner in view of Ma, Huang, Laffend, and Weisenborn does not teach or suggest that the glp promoter is a variant set forth in SEQ ID NO: 5 (Claim 24).
However, the applicable teachings and obviousness rationale of utilizing a glp promoter variant of the claimed SEQ ID NO: 5 is discussed above as applied to claims 6-7 in view of Weisenborn and L19201.1.
Therefore, it would have been obvious to have used the glpFK promoter comprising 95% identity to the claimed SEQ ID NO: 5, described by L19201.1, because it would have amounted to simple substitution of one known glpFK promoter for another. Because the two glpFK promoters are drawn towards the same promoter from the same organism, then it would have been predictable to have used the claimed variant of SEQ ID NO: 5 as the heterologous promoter in order to drive expression of the GDP-fucose biosynthetic pathway genes.
Allowable Subject Mater
Regarding claims 3, 9, 13, 15, 22, and 25, the instant specification teaches that the claimed SEQ ID NO: 7 is drawn towards an α1,3/4-fucosyl transferase mutant, termed “FutA_mut2” in which Ala (A) at position 128 is substituted by Asn (N), His (H) at position 129 is substituted by Glu (E), Asp (D) at position 148 is substituted by Gly (G) and Tyr (Y) at position 221 is substituted by Cys (C) (pg. 5). The instant specification teaches that when the claimed SEQ ID NO: 7 is expressed within E. coli cells, much higher LNFP-V titers were produced (i.e., 300%, 150%, and 200% more LNFP-V titers) than a reference strain 4 expressing a fucosyltransferase enzyme known from prior art in such constructs (pg. 20).
Accordingly, the claimed SEQ ID NO: 7 is not drawn towards a naturally occurring product and the instant specification provides adequate written description support for the claimed microorganism comprising the SEQ ID NO: 7.
Regarding the closest prior art, the closest prior art is Taylor (PG Pub No. US 2002/0164749 A1).
Taylor is drawn towards an invention concerned with bacterial fucosyltransferases (Abstract). Taylor teaches the use of a polypeptide that has 98.6% identity to the claimed SEQ ID NO: 7 (pg. 18-21; see SEQ ID NO: 6 in previously attached sequence alignment).
However, neither Taylor nor the prior art teaches or suggests that the polypeptide can be mutated in such a manner as to arrive at the instantly claimed SEQ ID NO: 7.
Therefore, the claimed SEQ ID NO: 7 is both novel and non-obvious in view of the closest prior art.
Therefore, claims 3, 9, 13, 15, 22, and 25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 15, because the claim is an independent claim as requires the claimed SEQ ID NO: 7, the claim is allowed for the reasons set forth above.
Response to Arguments
Applicant's arguments filed 17 July 2026 have been fully considered but they are not persuasive.
Applicant alleges that the Office utilizes Applicant’s disclosure as a roadmap to assert the obviousness of combining the Baumgärtner, Ma, and Yu references as described above as applied to claim 1 (Remarks; pg. 6).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant alleges that one of ordinary skill in the art would not have looked to the disclosure of Ma for the supplying of the claimed SEQ ID NO: 1 because the α1,3/4- fucosyltransferase of Ma does not share sequence identity with the α1,3/4- fucosyltransferase disclosed in Baumgärtner (Remarks; pg. 6). Applicant alleges that because there are over 67 thousand Uniprot entries and over 268 thousands NCBI entries for the phrase “fucosyltransferases”, a person of ordinary skill in the art would have had no reason to select the α1,3/4- fucosyltransferase of Ma and the Office Action failed to address why one of ordinary skill in the art would have chosen the specific α1,3/4- fucosyltransferase of Ma (Remarks; pg. 6). Applicant alleges that taking the Office Action’s logic on its face, all 268 thousand fucosyltransferases with a “common function” listed in NCBI would be obvious (Remarks; pg. 7-8).
MPEP 2144 teaches that the references do not have to explicitly suggest to combine the teachings. Rather, establishing a prima facie case of obviousness requires a clear articulation of a rationale for combining the teachings of the references, and such rationale has been provided in the rejection above. In the instant case, as required by MPEP 2143, the Office Action has articulated that the substituted components and their functions were known in the art and a finding that one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. Thus, the combination of Baumgärtner, Ma, and Yu renders obvious the claimed invention because the modification to Baumgärtner is a simple substitution of one known element for another to obtain predictable results. Additionally, Applicant’s arguments with respect to the 268 thousand “fucosyltransferases” listed in NCBI are moot because the simple substitution alleged in the rejection of record is drawn towards the substitution of an α1,3/4- fucosyltransferase, not merely a ”fucosyltransferase”. A person of ordinary skill in the art would have expected the simple substitution of the α1,3/4- fucosyltransferase to have predictably resulted in the α1,3/4- fucosyltransferase functioning within the recombinant microorganism to produce LNFP-V because Baumgärtner teaches that the enzyme can actively be utilized in a pathway to produce LNFP-V.
Applicant alleges that a skilled artisan would not enjoy a reasonable expectation of success because the disclosure of Yu teaches the genomic integration of a α1,3/4- fucosyltransferase was utilized in a method of purifying the α1,3/4- fructosyltransferase in an in vitro method; therefore, the method of Yu would not inform whether an active form of the enzyme could be successfully expressed in a microorganism configured to produce LNFP-V (Remarks; pg. 7). Applicant alleges that the Martin paper cited in Baumgärtner is drawn towards an in vitro process while the instant claim is drawn towards a recombinant microorganism; therefore, a skilled artisan would not expect the same successful production of LNFP-V within the claimed microorganism because in vivo and in vitro processes are fundamentally different (Remarks; pg. 7).
These arguments are not found persuasive because the disclose of Yu was merely relied upon for the teachings of the successful genomic integration and expression of an α1,3/4- fructosyltransferase within E. coli cells. As discussed above, it is the disclosure of Baumgärtner that teaches that “for the in vivo synthesis of fucosylated LNT with a Lewis A structure, an α1,3/4- or α1,4-fucosyltransferase activity is needed” (pg. 6800). Thus, it is the disclosure of the combination of the cited references that provides the reasonable expectation of success in utilizing the claimed enzyme in an in vivo process. The combination of the disclosures of Baumgärtner and Yu renders obvious the genomic integration and successful expression of a α1,3/4- fructosyltransferase in vivo.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Additionally, MPEP 716.01(c) makes clear that arguments of counsel cannot take the place of evidence in the record. In the instant case, Baumgärtner teaches that α1,3/4- fructosyltransferase can be utilized in the pathway in order to allow for the production of LNFP-V; thus, absent some evidence on the record a person of ordinary skill in the art would have expected that expressing the α1,3/4- fructosyltransferase in vivo would have resulted in the same production of LNFP-V through the same pathway as seen in vitro.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached Mon-Fri, 9AM-5PM (EDT/EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights