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 .
Election/Restrictions
Applicant's election with traverse of claims 9-10, and the species election of lacto-N-tetraose (LNT) in claim 10, in the reply filed on 11/10/2025 is acknowledged. The traversal is on the ground(s) that the claims of Groups I and Ill are related as a product and a process for manufacture of said product, and no objection to unity of invention was raised at any point of the PCT phase. This is not found persuasive because the instant application is a national stage application submitted under 35 U.S.C. 371, and therefore requires unity of invention analysis rather than the independent and distinct analysis required for applications filed under 35 U.S.C. 111(a). Applicant is directed to MPEP § 823. Further, the United States Patent and Trademark Office is not bound by the lack of unity determination by another ISA. 37 C.F.R. 1.484 states that the international preliminary examination is a non-binding opinion. Additionally, 37 C.F.R. 1.499 states that, if the Examiner finds that a national stage application lacks unity of invention under 37 C.F.R. 1.475, the Examiner may in an Office action require the applicant in the response to that action to elect the invention to which the claims shall be restricted. Thus, the determination of lack of unity is proper under the PCT treaty.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/10/2025.
In view of the prior art search, the species election is withdrawn.
Priority
This application is a 371 of PCT/EP2021/087337 (12/22/2021) which claims priority to EP20216485.1 (12/22/2020) as reflected in the filing receipt issued on 6/5/2025.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 2/26/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The information disclosure statement filed 6/20/2024 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. It has been placed in the application file, but the information referred to therein has not been considered.
Claim Rejections - 35 USC § 102
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.
Claims 9-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beauprez et al., US 20180066294 A1.
Claim 9 requires a genetically engineered microbial cell according to claim 1. As claim 1 is withdrawn, claim 9 is rewritten here for clarity to include all the limitations of claim 1:
A method for producing an oligosaccharide of interest comprising:
providing a genetically engineered microbial cell for the production of an oligosaccharide of interest, wherein said microbial cell comprises a lactose permease for internalizing exogenous lactose, and wherein said lactose permease is a variant of the E. coli lactose permease LacY which exhibits a reduced internalization of lactose as compared to E. coli wild-type LacY;
cultivating the genetically engineered microbial cell in the presence of exogenous lactose in a medium and under conditions allowing the cell to intracellularly synthesize the oligosaccharide of interest; and
recovering the oligosaccharide of interest from the culture medium or the cell.
Regarding claim 9, Beauprez teaches a method of producing an oligosaccharide of interest by providing a genetically engineered microbial cell that resists lactose killing (p. 1 para. 1). Beauprez teaches that the engineered microbes take up lactose and convert lactose to human milk oligosaccharides (p. 5 para. 68). Beauprez teaches cultivating the microbe in the presence of exogenous lactose in a medium (p. 6 para. 83; p. 11 para. 148) under conditions wherein the microbe can intracellularly synthesize the oligosaccharide (p. 5 para. 68). Beauprez teaches that the microbial cells produce the oligosaccharides of interest and the oligosaccharides are accumulated and measured by HPLC, i.e. recovered from the cell or culture medium for analysis (p. 7 para. 92; p. 11 para. 149).
Beauprez teaches a genetically engineered microbial cell for the production of an oligosaccharide of interest (p. 1 para. 1). Beauprez teaches that the microbial cell comprises a lactose transporter, which may be a lactose permease such as lacY (p. 3 para. 50; p. 4 para. 56; p. 9 para. 126). Beauprez teaches modifying E. coli lacY to develop a mutant (variant) strain which expresses lactose permease and resists lactose killing (p. 10 para. 140-141). Beauprez teaches selecting microorganisms with variant lactose transporters (i.e. lacY) which retain at least 50% of lactose influx compared to the wild type transporter, i.e. reduced internalization of lactose (p. 3 para. 51). Thus, Beauprez teaches a method according to claim 9, wherein a microbial cell according to claim 1 is cultivated to produce an oligosaccharide of interest.
Regarding claim 10, Beauprez teaches that the oligosaccharide produced by the engineered microorganism may be 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), 2',3-
difucosyllactose (DFL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose II (LNFP-II), lacto-N-fucopentaose III (LNFP-III), lacto-N-hexaose (LNH), lacto-N-neohexaose (LNnH), para- lacto-N-hexaose (paraLNH), lacto-N-difucosylhexaose I, lacto-N-difucosylhexaose II, lacto-N-neodifucohexaose I, 3'-sialyllactose (3-SL), 6'-sialyllactose (6-SL) (p. 3 para. 49; p. 5 para. 68).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 9 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 10-11 of copending Application No. 17/618,254 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to methods of producing oligosaccharides using genetically modified cells.
Regarding instant claims 9 and 10, claims 1 and 10 of ‘254 recite a method for production of fucosylated oligosaccharides (i.e. 2'-fucosyllactose, 3-fucosyllactose) comprising providing a Bacillus cell that is genetically engineered to possess a lactose permease, cultivating the cell in conditions permissive for fucosylated oligosaccharide production, and retrieving the oligosaccharide form the medium or cell. Claim 11 of ‘254 recites that the media contains lactose. Claim 3 of ‘254 recites that the lactose permease in the genetically engineered cell is E. coli LacY or a functional variant thereof. The specification of ‘254, p. 11, states that “functional variant” includes variants which possess an increased or decreased activity as compared to the activity of the referenced protein/polypeptide. Thus, a functional variant of LacY may possess decreased activity, or reduced internalization of lactose compared to wild type.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 9 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-14, 20, and 22 of copending Application No. 17/639,729 in view of Beauprez et al., US20180066294A1.
Regarding instant claims 9 and 10, claim 13 of ‘729 recites a method for production of a sialylated oligosaccharide (i.e. 3'-sialyllactose, 6'-sialyllactose)., comprising providing a genetically engineered Bacillus cell engineered to possess a lactose permease and cultivating in a fermentation broth under conditions permissive for the production of the oligosaccharide. Claim 14 of ‘729 recites that the fermentation broth contains lactose, i.e. exogenous lactose. Claim 20 of ‘729 recites retrieving (recovering) the oligosaccharide from the medium or cell. Claim 22 of ‘729 recites that the lactose permease is E. coli LacY.
‘729 does not recite a genetically engineered microbial cell wherein the lactose permease is a variant of LacY with reduced internalization of lactose compared to wild-type. However, these features are taught by Beauprez.
Beauprez teaches a method of producing an oligosaccharide of interest by providing a genetically engineered microbial cell that resists lactose killing (p. 1 para. 1). Beauprez teaches that the microbial cell comprises a lactose transporter, which may be a lactose permease such as lacY (p. 3 para. 50; p. 4 para. 56; p. 9 para. 126). Beauprez teaches modifying E. coli lacY to develop a mutant (variant) strain which expresses lactose permease and resists lactose killing (p. 10 para. 140-141). Beauprez teaches selecting microorganisms with variant lactose transporters (i.e. lacY) which retain at least 50% of lactose influx compared to the wild type transporter, i.e. reduced internalization of lactose (p. 3 para. 51). Thus, Beauprez teaches a method according to claim 9, wherein a microbial cell according to claim 1 is cultivated to produce an oligosaccharide of interest.
It would have been obvious for a skilled artisan that a genetically modified microbial cell with a variant LacY that has reduced lactose influx as taught by Beauprez could be used in place of the wild-type LacY recited in the method of producing oligosaccharides of ‘729. A skilled artisan would have been motivated to do so, with reasonable expectation of success, given the teachings of Beauprez that the variant microbial cells have the benefit of resisting lactose killing and can be successfully cultivated to produce oligosaccharides (see Beauprez p. 1 para. 1; p. 5 para. 68).
This is a provisional nonstatutory double patenting rejection.
Claims 9 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, and 15 of copending Application No. 16/634,000 in view of Beauprez et al., US20180066294A1.
Regarding instant claims 9 and 10, claim 1 of ‘000 recites a method for producing one or more sialylated oligosaccharides by whole cell fermentation, comprising providing at least one genetically engineered cell, cultivating the at least one cell in a fermentation broth and under conditions permissive for the production of said sialylated oligosaccharide and recovering said sialylated oligosaccharide from the fermentation broth. Claim 2 of ‘000 recites that the oligosaccharide includes LST-a, LST-b, LST-c, and DSLNT. Claim 6 of ‘000 recites that the cell is cultivated in the presence of lactose. Claim 15 of ’000 recites that cell comprises a functional lactose permease.
‘000 does not recite a genetically engineered microbial cell wherein the lactose permease is a variant of LacY with reduced internalization of lactose compared to wild-type. However, these features are taught by Beauprez, as set forth above.
It would have been obvious for a skilled artisan that a genetically modified microbial cell with a variant LacY that has reduced lactose influx as taught by Beauprez could be used in place of the wild-type LacY recited in the method of producing oligosaccharides of ‘000. A skilled artisan would have been motivated to do so, with reasonable expectation of success, given the teachings of Beauprez that the variant microbial cells have the benefit of resisting lactose killing and can be successfully cultivated to produce oligosaccharides (see Beauprez p. 1 para. 1; p. 5 para. 68).
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 9 and 10 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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/EMILY F EIX/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653