Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Application Status
This application is a CON of US patent application 16/634,593, filed on 10/30/2023, which was a 371 of PCT/EP2018/070857, filed on 08/01/2018.
Claims 1, 3-7, 9-11, 12-15 and 16-18 are currently pending in the instant application.
In response to a previous Office action, an Allowability Notice Office action (mailed on 03/13/2026), Applicants filed a new Information Disclosure Statement (IDS) on 03/24/2026 with a transmittal letter is acknowledged.
Claims 12-15 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/24/2026 has been entered.
Claims 1, 3-7, 9-11 and 16-18 are present for examination.
Priority
Acknowledgement is made of applicants claim for domestic priority of US patent application 16/634,59, filed on 01/28/2020, and Foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application GERMANY 17184232.1, filed on 08/01/2017 without English translation.
New-Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/24/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is considered by the examiner. The signed copy of IDS is enclosed herewith.
New-Claim Rejections - 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
According to MPEP 2143:
“Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield
predictable results;
(B) Simple substitution of one known element for another to obtain predictable
results;
(C) Use of known technique to improve similar devices (methods, or products)
in the same way;
(D) Applying a known technique to a known device (method, or product) ready
for improvement to yield predictable results;
(E) “ Obvious to try ” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in
either the same field or a different one based on design incentives or other market
forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art
reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.”
Claims 1, 3-7, 9-11 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Heidtman et al. (Alpha (1,3) fructosyltransferases for use in the production of fucosylated oligosaccharides. WO 2016/040531 A1, publication 03/17/2016, claim benefit of 62/047,851, filed on 09/09/2014) in view of Choi et al. (Solubilization and Iterative Saturation Mutagenesis of α1,3-fucosyltransferase from Helicobacter pylori to enhance its catalytic efficiency. Biotechnol. Bioeng. (2016), 113(8): 1666-1675), Lacmata et al. (A novel autolysis system controlled by magnesium and its application to poly(3-hydroxypropionate) production in engineered Escherichia coli. Bioengineered (2017), 8(5): 594-599), and Lee et al. (Soluble expression of the fructosyltransferases gene from Helicobacter pylori in Escherichia coli by co-expression of molecular chaperones. Microbiol. Biotechnol. Lett. (2015), 43(3), 212-218).
The Broadest Reasonable Interpretation (BRI) of claim 1, which is drawn to a genetically modified bacterium for the production of 2-fucosyllactose, wherein the bacterium, comprises an exogenous gene encoding a fructosyltransferases including alpha-1,2-fucosyltransferase and/or alpha-1,3-fucosyltransferase, and an auto-inducible lysis system.
Regarding claims 1, 3-7, 9-11 and 16-18, Heidtman et al. teach a recombinant, genetically altered or engineered bacterial host E. coli expressing α-1,2-fucosyltransferase gene encoding enzyme for the production of 2'-fucosyllactose, a human milk oligosaccharide (HMOS) as claimed, wherein said α-1,2-fucosyltransferase gene futC derived from Helicobacter pylori wherein the bacterium is modified to maintain its ability to transport lactose from the culture medium via LacY gene encoding lactose permease overexpression by introducing exogenous LacY gene (see, para 36) by putting strong promoter in front of LacY gene, and is deleted for the wild-type copy of the lacZ (β-galactosidase) gene responsible for lactose catabolism, as well as deletion of lacI encoding lactose (lac) operon and deletion of lacA gene in order to eliminate undesired acetyl-lactose production, wherein said genetically modified E. coli host cell also comprises exogenous rcsA gene from E. coli for the overexpression and deletion of genes including lon gene, and wcaJ gene, (see, para 3, 6, 8, 16, 24, 25, 28, 30, 33, 34, 35, 36, 40, 44, 49, 62-64, 79-80, 97110, 142, 144, 145 and Fig. 2). Heidtman et al. also teach the method for producing HMOS by culturing a recombinant bacterium in a medium comprising lactose, and the HMOS is purified and subsequently formulated into animal feed or food (para 49). Heidtman et al. also teach expression of synthetic genes comprises ribosomal binding site, are codon optimized for expression in a host bacterial production strain E. coli (see, para 117). Heidtman et al. further teach comprises deletion of the wild-type copy of the lacZ (β-galactosidase) gene responsible for lactose catabolism, as well as deletion of lacI encoding lactose (lac) operon and deletion of lacA gene, the unable to cleave lactose into glucose and galactose, is the inherent property of recombinant, genetically altered or engineered bacterial host E. coli cell of Heidtman et al. Since the Office does not have the facilities for examining and comparing applicants' microorganism for producing 3'-fucosyllactose, a human milk oligosaccharide (HMOS) by 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. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Heidtman et al. do not teach the bacterium comprises Mg2+ regulated inducible lysis system (for claims 1, 3), and the bacterium comprises a heterologous gene encoding a chaperone human Hsp70 (for claim 10).
However, Lacmata et al. teach a novel autolysis system controlled by magnesium and its application to poly(3-hydroxypropionate) production in engineered Escherichia coli, and further teach the release of intracellular products efficiently a novel autolysis system strictly controlled with magnesium was constructed and applied to poly(3-hydroxypropionate) production in engineered Escherichia coli, wherein the autolysis system was constructed by inserting the 50 untranslated region (50 UTR) behind promoter PmgtA with lysis genes (S, R, and Rz, from E. coli) overexpressed, and the autolysis system functioned well (lysis efficiency of more than 90%) in the P3HP producer with double plasmids containing lysis genes and P3HP biosynthesis genes (see, abstract, title, and Fig. 3).
Lacmata et al. do not teach the microorganism comprises a heterologous gene encoding a chaperone human Hsp70 (for claim 10).
However, Lee et al. teach soluble expression of the fructosyltransferases gene FucT2 from Helicobacter pylori in Escherichia coli by co-expression of molecular chaperones including Hsp70 to improve the production of amount of FucT2 enzyme and stabilizing FucT2 enzyme (abstract, pg. 213, right Col, para 2, pg. 216, right Col, para 2), wherein the FucT2 enzyme is the key enzyme for the production of 2'-fucosyllactose, a human milk oligosaccharide (HMOS) as claimed.
Lee et al. clearly teach soluble expression of the fucosyltransferases gene FucT2 from Helicobacter pylori in Escherichia coli by co-expression of molecular chaperones including Hsp70 to improve the production of amount of FucT2 enzyme and stabilizing FucT2 enzyme (abstract, pg. 213, right Col, para 2, pg. 216, right Col, para 2), wherein the FucT2 enzyme is the key enzyme for the production of 2'-fucosyllactose, a human milk oligosaccharide (HMOS) as claimed.
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the claimed invention as a whole before the effective filing date of the invention was made by combining the teachings of Heidtman et al. Lacmata et al., and Lee et al., to use codon optimized heterologous expression α1,2-fucosyltransferase from Helicobacter pylori in Escherichia coli to enhance its catalytic efficiency the enzyme as taught by Heidtman et al., and using a novel autolysis system controlled by magnesium and its application to poly(3-hydroxypropionate) production in engineered Escherichia coli as taught by Lacmata et al. and using molecular chaperones including Hsp70 protein and co-expressing with fucosyltransferases gene as taught by Lee et al. and modify Heidtman et al. to make a recombinant E. coli host cell by expressing Mg2+-regulated promoter to overexpress the fucosyltransferases gene and using auto-inducible Escherichia coli lysis system and overexpressing lysis gene from λ bacteriophage and using molecular chaperones including Hsp70 protein and co-expressing with fucosyltransferases gene for producing increased amount of fucosyltransferases enzyme and ultimate produce increased amount of 2'-fucosyllactose or 3’-fucosyllactose, a human milk oligosaccharide (HMOS) to arrive the claimed invention.
One of ordinary skilled in the art would have been motivated to use Mg2+-regulated promoter to overexpress the fucosyltransferases gene by adding magnesium ion, and using auto-inducible Escherichia coli lysis system and overexpressing lysis gene from bacteriophage to overexpress the fucosyltransferases gene for producing increased amount of 2'-fucosyllactose
a human milk oligosaccharide (HMOS) to be used in infant nutrition, medical nutrition, functional foods and animal feeds, which is pharmaceutically, therapeutically, commercially, and financially beneficial. One of an ordinary skilled in the art would have been further motivated to overexpress auto-lysis gene from bacteriophage and molecular chaperones including Hsp70 protein in the recombinant host cell to overexpress and release functional fucosyltransferases enzymes and ultimate produce increased amount of 2'-fucosyllactose or 3’-fucosyllactose, a human milk oligosaccharide (HMOS), to be used in infant nutrition, medical nutrition, functional foods and animal feeds, which is pharmaceutically, therapeutically, commercially, and financially beneficial.
One of ordinary skilled in the art would have a reasonable expectation of success because Heidtman et al. could successfully produce 2'-fucosyllactose or 3’-fucosyllactose, a human milk oligosaccharide (HMOS) in a recombinant E. coli host cell overexpressing fucosyltransferases enzymes.
Thus, the above references render the claims prima facie obvious to one of ordinary skill in the art.
Conclusion
Status of the claims:
Claims 1, 3-7, 9-11 and 16-18are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Primary Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656
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