Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response to restriction letter of 3/20/26 is acknowledged. Applicant elected Group I, claims 81-100, 102-103, 105-107, without traverse as well as the following species: a method of producing oligosaccharides (oligos) comprising a purification step comprising removing salts etc. and concentrating the oligos (species A); a method of preparing an oligo mixture wherein step (i) is according to claim 86 (species 1) and step (ii) is according to claim 88 (species (a)).
Claims 101, 104 are hereby withdrawn as drawn to non-elected subject matter. Species B-C and 2-8 and (b)-(e) are hereby rejoined with the elected species.
DETAILED ACTION
In view of applicant’s election, the following claims are under examination: claims 81-100, 102-103, 105-106 are under examination on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 82 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. Claim 82 does not make sense as step (iii) inherently requires a concertation step (ii).
Claim 88 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. Claim 88 is confusing because applicant appears to describes steps involved in claim 81 step (ii). However, applicant utilizes the term “use for” or “use of” inconsistently. For example, the phrase “cation exchange adsorbent resin” is not preceded by any of said phrases. Appropriate clarification is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 81-100, 102-103, 105-107 are rejected under 35 U.S.C. 103 as being unpatentable over Pedersen et al., “Pedersen” (US2021/0102216, 4/8/21, see also its corresponding US patent No. 11,608,504) in view of Chassagne et al., “Chassagne” (WO 2017182965, 10/2017). From now on, said patent publication together with said world patent will be utilized to cited relevant text in this rejection.
Pedersen in its abstract, teaches recombining production of biological molecules in host cells. It further provides nucleic acid constructs that allow to modify expression of a desired gene using both in vitro and in vivo gene expression systems. The constructs can advantageously be used to produce a variety of biological molecules recombinantly in industrial scales, e.g. human milk oligosaccharides (HMOs), said HMOs comprising both neutral or charged (see [0071]) oligosaccharides (oligos).
In [0163], according to said publication said HMOs are purified.
In [0171], Pederson also refers to a minimal salt medium used to grow some of its host cells.
Said publication does not explicitly mention any clarification of fermentation. Chassagne in its abstract teaches the following:
“The invention relates to a method for obtaining an N-acetylglucosamine containing neutral oligosaccharide from a fermentation broth, wherein said oligosaccharide is produced by culturing a genetically modified microorganism capable of producing said oligosaccharide from an internalized carbohydrate precursor, comprising the steps of: i) ultrafiltration (UF), preferably to separate biomass from the broth, ii) nanofiltration (NF), preferably to concentrate said oligosaccharide in the broth and/or reduce an inorganic salt content of the broth, and iii) treating the broth with an ion exchange resin, preferably to remove charged materials, and/or subjecting the broth to chromatography, preferably to remove hydrophobic impurities.”.
In section 2.2.1., step (i), Chassage discloses that:
i) the separation/purification of the N-acetylglucosamine containing neutral oligosaccharide
According to step i) of the method, the broth obtained from fermentation is subjected to ultrafiltration, preferably as a first step. The fermentation broth typically contains, besides the N- acetylglucosamine containing neutral oligosaccharides produced, the biomass of the cells of the used microorganism together with proteins, protein fragments, DNA, endotoxins, biogenic amines, inorganic salts, unreacted carbohydrate acceptors such as lactose, sugar-like by-products, monosaccharides, colorizing bodies, etc. The ultrafiltration step is to separate the biomass and, preferably, also high molecular weight suspended solids from the soluble components of the broth which pass through the ultrafiltration membrane in the permeate. This UF permeate (UFP) is an aqueous solution containing the produced N-acetylglucosamine containing neutral oligosaccharide. This step may be considered to result in clarified fermentation broth.
Any conventional ultrafiltration membrane can be used having a molecular weight cut-off (MWCO) range between about 1 and about 500 kDa, such as 10-250, 50-100, 200-500, 100-250, 1-100, 1-50, 10-25, 1-5 kDa, or any other suitable sub-ranges. The membrane material can be a ceramic or made of a synthetic or natural polymer, e.g. polysulfone, polypropylene, cellulose acetate or polylactic acid. The ultrafiltration step can be applied in dead-end or cross-flow mode. This step i) may comprise more than one ultrafiltration step using membranes with different MWCO, e.g. using two ultrafiltration separations wherein the first membrane has a higher MWCO than that of the second membrane. This arrangement may provide a better separation efficacy of the higher molecular weight components of the broth. After this separation step the permeate contains materials that have a molecular weight lower than the MWCO of the second membrane, including the N- acetylglucosamine containing neutral oligosaccharide of interest.
In one embodiment, the fermentation broth is ultrafiltered using a membrane having a MWCO of 5- 30 kDa, such as 10-25, 15 or 20 kDa. 2.2.2. Step ii) of the separation/purification of the N-acetylglucosamine containing neutral oligosaccharide.
In Step (ii) Chassagne recites:
“Step ii) of the method comprises a nanofiltration step. Step ii) may follow step i) or step iii) (described below), preferably step i). This nanofiltration step may advantageously be used to concentrate the previously treated fermentation broth having the N-acetylglucosamine containing neutral oligosaccharide and/or to remove ions, mainly monovalent ions, and organic materials having a molecular weight lower than that of the N-acetylglucosamine containing neutral oligosaccharide, such as monosaccharides. The nanofiltration membrane has a MWCO that ensures the retention of the N-acetylglucosamine containing neutral oligosaccharide of interest, that is its MWCO is lower than that of the ultrafiltration membrane(s) used in step i), and around 25-50 % of the molecular weight of the N-acetylglucosamine containing neutral oligosaccharide. In this regard the N-acetylglucosamine containing neutral oligosaccharide is accumulated in the NF retentate (NFR). The nanofiltration can be combined with diafiltration with water to remove, or to reduce the amount of, permeable salts such as monovalent ions more effectively.
In one embodiment, step ii) follows step i), that is the UF permeate obtained in step i) is nanofiltered without diafiltration, and the NF retentate containing the produced N- acetylglucosamine containing neutral oligosaccharide is collected and subjected to further separation step(s) of the method.
In one embodiment, step ii) follows step i), that is the UF permeate obtained in step i) is nanofiltered followed by diafiltration, and the NF retentate containing the produced N- acetylglucosamine containing neutral oligosaccharide is collected and subjected to further separation step(s) of the method.
In 4 paragraphs above section 2.2.3.2, Chassagne mentions that to bring down the salt electrolyte content, electrodialysis is recommended.
Said Chassagne patent in step (iii) mentions:
2.2.3.1. Step iii): treatment with an ion exchange resin
In step iii), the aqueous solution of the N-acetylglucosamine containing neutral oligosaccharide from step i) or ii) may be further purified by means of an ion exchange resin. Salts, color bodies and/or charged macromolecules can be removed by treatment with resin.
According to one embodiment, the ion exchange resin is an anion exchange resin, preferably a weakly basic anion exchange resin. In this step the negatively charged materials can be removed from the pre-treated solution as they bind to the resin. The aqueous solution of the N- acetylglucosamine containing neutral oligosaccharide is contacted with an anion exchange resin in any suitable manner which would allow the negatively charged materials to be adsorbed onto the anion exchange resin, and the N-acetylglucosamine containing neutral oligosaccharide to pass through. The resulting liquid, after contacting with the anion exchange resin, contains primarily water, cations and neutral carbohydrates like the carbohydrate acceptor previously added to the fermentation culture to be glycosylated, e.g. lactose (if still left after one or more previous purification steps).
According to another embodiment, the ion exchange resin is a cation exchange resin, preferably a strongly acidic cation exchange resin. In this step the positively charged materials can be removed from the pre-treated solution as they bind to the resin. The solution of the N-acetylglucosamine containing neutral oligosaccharide is contacted with the cation exchange resin in any suitable manner which would allow positively charged materials to be adsorbed onto the cation exchange resin, and the N-acetylglucosamine containing neutral oligosaccharide to pass through. The resulting liquid, after contacting with the cation exchange resin, contains the N-acetylglucosamine containing neutral oligosaccharide besides anions and neutral carbohydrates like the carbohydrate acceptor previously added to the fermentation culture to be glycosylated, e.g. lactose (if still left after one or more previous purification steps).
One of the ion exchange resin treatments disclosed above in step iii) may be sufficient to obtain the N-acetylglucosamine containing neutral oligosaccharide in a required purity. If necessary, both cation and anion exchange resin chromatography, in any order, can be applied.
When using an ion exchange resin, its degree of crosslinking can be chosen depending on the operating conditions of the ion exchange column. A highly crosslinked resin offers the advantage of durability and a high degree of mechanical integrity, however suffers from a decreased porosity and a drop off in mass-transfer. A low-crosslinked resin is more fragile and tends to swell by absorption of mobile phase. The particle size of the ion exchange resin is selected to allow an efficient flow of the eluent, while the charged materials are still effectively removed. A suitable flow rate may also be obtained by applying a negative pressure to the eluting end of the column or a positive pressure to the loading end of the column, and collecting the eluent. A combination of both positive and negative pressure may also be used. The ion exchange treatment can be carried out in a conventional manner, e.g. batch-wise or continuously.
Before the effective filing of this application, it would have been obvious to one of ordinary skill in the art to start with the method of Pederson and purify its fermentation broth HMOs, utilizing the purification method of Chassagne, which suggests purifying its transfected host cell broth by removing salts, media components etc. as explained above, inherently resulting in a clarified broth followed by filtering or concentrating said HMO’s.
One of ordinary skill in the art has a reasonable expectation of success in purifying the recombinant HMOs of Pederson according to the instructions of Chassagne because such procedures have been fully characterized and established in the prior art, before the effective filing of this application.
Applicant is also reminded that depending on the nature/structure of recombinant oligosaccharides (or mixture thereof) to be purified, one of ordinary skill can reasonably envisage any combination of salt removal and concentration steps in any permutations and/or combinations, based on the combined teachings (techniques) of Pedersen in view of Chassagne, in order to reach the desired levels of purity.
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 81-100, 102-103, 105-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 119-122 of copending Application No. 18/040356. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of claims in said copending application overlaps with instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 81-100, 102-103, 105-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9,15-22, 26-31, 33-36, 38, 40, 42-45 of copending Application No. 18/040,064. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of claims in said copending application overlaps with the scope of instant claims
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 81-100, 102-103, 105-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 124-131 of copending Application No. 18/040,378. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of claims in the copending application (generic) embraces the scope of instant claims (species).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 81-100, 102-103, 105-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 56-58 of copending Application No. 18/167,687. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of claims in said copending application overlaps with the scope of instant claims.
Claims 81-100, 102-103, 105-107 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 84-127 of copending Application No. 18/0401,054. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of claims in the copending application (generic) embraces the scope of instant claims (species).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex.
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/MARYAM MONSHIPOURI/ Primary Examiner, Art Unit 1651
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