The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received January 30, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 1-83, 118, 128, 130-138, 140 are canceled. Claims 142 is withdrawn. Claims 84-117, 119-127, 129, 139, 141, 143-146 are under consideration.
Priority: This application is a 371 of PCT/EP2021/072273, filed August 10, 2021, which claims benefit of foreign application EP 20190210.3, filed August 10, 2020. A copy of the foreign priority document has been received in the instant application on February 8, 2023 and is in the English language.
Objections and Rejections
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 106 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 106 further recites "the ultrafiltration permeate" is alternatively “nanofiltered” or “nanofiltered and electrodialysed” in step ii). Claim 106 is dependent on claim 84, where claim 84, step ii) already recites the step comprises nanofiltration. Further clarification and/or correction is requested.
Reply: In view of Applicants’ amendments, instant claim 106 remains rejected under 35 U.S.C. 112(b) for the reasons noted above.
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.
Claims 84-110, 112-115, 117, 119-127, 129, 139, 141, 143-146 are rejected under 35 U.S.C. 103 as being unpatentable over Matwiejuk et al. (WO 2017152918; previously cited). Matwiejuk et al. disclose a method for separating sialylated oligosaccharides from a fermentation broth obtained by culturing a genetically modified microorganism producing said sialylated oligosaccharides, comprising the steps of (i) ultrafiltration; (ii) nanofiltration; (iii) optional activated charcoal treatment; and (iv) treatment with a strong cation exchange resin (at least abstract, p. 19 lines 1-9, p. 20 lines 6-11). Matwiejuk et al. disclose the nanofiltration membrane has a MWCO (molecular weight cut-off) that is the lower than that of the ultrafiltration membrane(s) (p. 10 lines 21-23), where in one embodiment, the ultrafiltration membrane has a MWCO of 5-30 Da (p. 8 lines 13-14), and the nanofiltration membrane has a MWCO of about 300 Da (p. 10 lines 25-26). Matwiejuk et al. disclose the fermentation broth typically contains, besides the sialylated oligosaccharide, the biomass of the cells together with proteins, protein fragments, DNA, endotoxins, salts, etc. (p. 7 lines 23-25). Matwiejuk et al. differ from the claimed method by not explicitly reciting the purity of the separated or purified oligosaccharide solution. However, since Matwiejuk et al. disclose a method for separating oligosaccharides from a fermentation broth comprising the same components recited and further comprising the same steps and features recited to purify the oligosaccharides, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that Matwiejuk et al. can be deemed to disclose that the oligosaccharide have the initial recited purities in the fermentation broth and the separated or purified oligosaccharides from the fermentation broth are a purity of >80% on total dry solid. Therefore, Matwiejuk et al. can be deemed to render obvious the method of instant claims 84, 93-94, 95-97, 98, 101, 102-103, 105-109, 113, 119, 129, 145.
Regarding instant claims 85, 104, 112, Matwiejuk et al. disclose step (i) comprises two consecutive ultrafiltrations and the molecular weight cut-ff of the first ultrafiltration membrane is higher than that of the second membrane (p. 19 lines 12-14).
Regarding instant claims 86, 94, 117, 119, 146, Matwiejuk et al. disclose step (iii) an activated charcoal treatment, where the activated charcoal treatment helps to remove colorizing agents and/or water soluble contaminants, such as salts (p. 11 lines 14-16), and where at least 90%-95% of sialylated oligosaccharides are obtained in a decolorized solution (p. 12 lines 10-12, 21-22). Since Matwiejuk et al. disclose treating the oligosaccharide solution with the same treatment steps recited, Matwiejuk et al. can be deemed to disclose an ash content of <10% on total dry solid.
Regarding instant claims 87-91, Matwiejuk et al. disclose the oligosaccharide is produced by culturing a genetically modified cell in a fermentation broth, where the genetically modified cell is E. coli (at least p. 4 lines 20 to p. 5 lines 4, p. 6 lines 10 to p. 7 lines 20, p. 15 lines 28 to p. 16 lines 3).
Regarding instant claim 92, Matwiejuk et al. disclose that the fermentation broth typically contains the biomass of the cells together with proteins, protein fragments, DNA, endotoxins, biogenic amines, inorganic salts, lactose, sugar-like by-products, sialic acid, colorizing bodies, etc. (p. 7 lines 23-25).
Regarding instant claims 99-100, 112-113, 115, Matwiejuk et al. disclose that the purified oligosaccharides can further be provided in a concentrated form by removing water, including by distillation, nanofiltration (p. 15 lines 24-27), where a further nanofiltration treatment is reasonably a sterile filtration (instant claim 115).
Regarding instant claim 110, Matwiejuk et al. disclose that the cationic exchange treatment eluate has a pH 6.7 (p. 18 lines 2-4).
Regarding instant claim 114, Matwiejuk et al. disclose after nanofiltration, the retentate from which the oligosaccharide solution is recovered shows a Brix of about 20-25 (p. 17 lines 15-16). Therefore, it would be obvious that the purified oligosaccharide after active charcoal treatment and cationic exchange treatment reasonably has a Brix value from about the recited 8 to about 75%.
Regarding instant claim 120, Matwiejuk et al. disclose the oligosaccharide is produced by culturing a genetically modified cell in a fermentation broth, where the genetically modified cell is E. coli (at least p. 4 lines 20 to p. 5 lines 4, p. 6 lines 10 to p. 7 lines 20, p. 15 lines 28 to p. 16 lines 3).
Regarding instant claim 121, Matwiejuk et al. disclose the sialylated oligosaccharide/sialylated lactoses are produced by a genetically modified microorganism which is a E. coli of LacY+LacZ- genotype (p. 6 lines 30 to p. 7 lines 4, p. 15 lines 28-30).
Regarding instant claims 122, 125-127, 129, Matwiejuk et al. disclose the isolated/purified sialylated oligosaccharide/sialylated lactoses can be spray-dried, freeze-dried, crystallized, or provided in the form of a syrup (p. 15 lines 15-27).
Regarding instant claims 123-124, Matwiejuk et al. disclose an oligosaccharide concentration 170-210 g/l after a first nanofiltration treatment at 45º C (p. 17 lines 19-20). As noted above, Matwiejuk et al. disclose the isolated/purified sialylated oligosaccharide/sialylated lactoses can be spray-dried, freeze-dried, crystallized, or provided in the form of a concentrated aqueous solution or syrup by removing water, e.g. by means of distillation, vacuum distillation, nanofiltration (p. 15 lines 15-27). Since Matwiejuk et al. disclose a method for separating oligosaccharides from a fermentation broth comprising the same components recited and further comprising the same steps and features recited to purify the oligosaccharides, where the isolated/purified sialylated oligosaccharide/sialylated lactoses can be spray-dried, freeze-dried, crystallized, or provided in the form of a concentrated aqueous solution or syrup by removing water, e.g. by means of distillation, vacuum distillation, nanofiltration, it would be obvious to arrive at the recited conditions for concentrating the purified/isolated oligosaccharides by nanofiltration by routine optimization and the recited conditions for crystallizing the purified/isolated oligosaccharides by routine optimization.
Regarding instant claims 129, 139, since Matwiejuk et al. disclose a method for separating oligosaccharides from a fermentation broth comprising the same components recited and further comprising the same steps and features recited to purify the oligosaccharides, Matwiejuk et al. can be deemed to disclose that the oligosaccharide have the initial recited purities in the fermentation broth and the separated or purified oligosaccharides from the fermentation broth are a purity of >80% being free of recombinant DNA and protein materials and having the recited conductivity.
Regarding instant claim 141, Matwiejuk et al. disclose there is interest in the preparation and commercialization of human milk oligosaccharides (HMOs), which includes the sialylated oligosaccharides purified and separated by the method of Matwiejuk et al. noted above (p. 1 lines 1-20). Therefore, it would have been obvious to one of ordinary skill to form a milk or food composition comprising the purified oligosaccharides obtained from the method of Matwiejuk et al. noted above.
Regarding instant claims 143-144, Matwiejuk et al. disclose the oligosaccharide solution comprises human milk oligosaccharide (p. 4 lines 3-7, p. 17-19). Additionally, since the Matwiejuk et al. disclose a method for separating oligosaccharides from a fermentation broth comprising the same components recited and further comprising the same steps and features recited to purify the oligosaccharides, Matwiejuk et al. can be deemed to disclose that the oligosaccharide saccharide comprises a neutral human milk oligosaccharide (instant claim 144).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that independent claim 84 encompasses purification of an oligosaccharide solution comprising a single oligosaccharide or multiple saccharides, as confirmed by dependent claim 95. Applicants assert that Matwiejuk et al. do not disclose or suggest the required combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange.
Applicants’ remarks are not persuasive. Instant claim 84 is essentially drawn to a method for purifying an oligosaccharide solution from a cultivation or fermentation broth obtained by cell cultivation or microbial fermentation, the method steps comprising i) clarifying the cultivation or fermentation broth; ii) nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that does not include anionic ion exchange, wherein a purified oligosaccharide solution at a purity of > 80% on total dry solid is obtained.
As noted in the 103 rejection above, Matwiejuk et al. disclose a method for separating sialylated oligosaccharides from a fermentation broth obtained by culturing a genetically modified microorganism producing said sialylated oligosaccharides, comprising the steps of (i) ultrafiltration; (ii) nanofiltration; (iii) optional activated charcoal treatment; and (iv) treatment with a strong cation exchange resin (at least abstract, p. 19 lines 1-9, p. 20 lines 6-11), where the nanofiltration membrane has a MWCO (molecular weight cut-off) that is the lower than that of the ultrafiltration membrane(s) (p. 10 lines 21-23), where in one embodiment, the ultrafiltration membrane has a MWCO of 5-30 Da (p. 8 lines 13-14), and the nanofiltration membrane has a MWCO of about 300 Da (p. 10 lines 25-26).
Matwiejuk et al. expressly disclose treatment with a strong cation exchange resin is an alternative to a strong anion exchange resin (p. 19 line 9).
Therefore, Matwiejuk et al. disclose a method for purifying an oligosaccharide solution obtained from microbial fermentation as recited in instant claim 84 and comprising the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange.
Therefore, it would be obvious that the oligosaccharide solution to be purified in Matwiejuk et al. is the same as the oligosaccharide solution being purified in instant claim 84 (and therefore dependent claim 95) because both the oligosaccharide solution of Matwiejuk et al. and the instant oligosaccharide solution are obtained from a microbial fermentation.
Applicants assert that Matwiejuk et al. do not disclose (1) any spray-dried powder, (2) any defined composition or final product corresponding to the rejected claims, (3) any mixture of structurally distinct human milk oligosaccharides, or (4) any nutritional composition or formulation.
Applicants’ remarks are not persuasive. The features (1) to (4) asserted by Applicants are not recited in instant claim 84. These features are recited in the dependent claims and are addressed in the 103 rejection over Matwiejuk et al. noted above.
Applicants then assert first, Matwiejuk et al. do not inherently produce mixtures of structurally distinct HMOs. Applicants assert that Matwiejuk et al. is directed to the isolation of targeted sialylated oligosaccharides and does not disclose that multiple structurally distinct HMOs – such as combinations of neutral and acidic HMOs – are retained together through purification. Applicants assert that inherency requires inevitability, not possibility, and the office action does not identify any disclosure establishing that Matwiejuk et al.’s process necessarily yields a mixture of structurally distinct HMOs.
Applicants’ remarks are not persuasive. As noted above, Matwiejuk et al. disclose a method for purifying an oligosaccharide solution obtained from microbial fermentation as also recited in instant claim 84 and comprising the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange.
Since Matwiejuk et al. disclose purifying the same oligosaccharide solution recited and purification by the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange, it would be obvious to one of ordinary skill in the art that the method of Matwiejuk et al. necessarily yields a mixture of structurally distinct HMOs because the same purification steps are being practiced on the same oligosaccharide solutions.
Applicants assert second, Matwiejuk et al. do not necessarily produce the claimed compositional ratios. Applicants assert that the reference contains no disclosure of relative proportions among different oligosaccharides in any purified product, nor any teaching that is purification steps control or preserve specific ratios.
Applicants’ remarks are not persuasive. The features or characteristics of the purified oligosaccharide recited in the dependent claims and asserted by Applicants are dependent or obtained by the method of instant claim 84. Therefore, since Matwiejuk et al. disclose purifying the same oligosaccharide solution recited and purification by the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange, it would be obvious to one of ordinary skill in the art that the method of Matwiejuk et al. necessarily yields the claimed compositional ratios because the same purification steps are being practiced on the same oligosaccharide solutions.
Applicants assert third, Matwiejuk et al. do not inherently produce the claimed purity and ash profiles.
Applicants’ remarks are not persuasive. The features or characteristics of the purified oligosaccharide, including the claimed purity and ash profiles, recited in the dependent claims and asserted by Applicants are dependent or obtained by the method of instant claim 84. In this instance, Matwiejuk et al. disclose purifying the same oligosaccharide solution recited and purification by the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange, as well as an activated charcoal treatment. Therefore, it would be obvious to one of ordinary skill in the art that the method of Matwiejuk et al. necessarily yields the claimed purity and ash profiles because the same purification steps are being practiced on the same oligosaccharide solutions.
Regarding Applicants’ remarks that procedurally, the office action does not provide a reasoned basis – grounded in Matwiejuk et al. itself – for modifying or extending the disclosed purification methods to arrive at the claimed subject matter, the remarks are not persuasive. In this instance and for the reasons already noted above, Matwiejuk et al. disclose a method for purifying an oligosaccharide solution obtained from microbial fermentation as recited in instant claim 84 and comprising the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange.
For at least these reasons, the 103 rejection is maintained.
Claims 84-117, 119-127, 129, 139, 141, 143-146 are rejected under 35 U.S.C. 103 as being unpatentable over EP 3524067 (EP ‘067) (previously cited). EP ‘067 discloses a process for purifying an aqueous solution containing at least one HMO from a fermentation broth obtained from cell cultivation or microbial fermentation, comprising i) removing the microbial cells from the fermentation broth to obtain a process stream; ii) subjecting the process stream to at least one ultrafiltration; iii) treating the process stream to at least one time with a cation exchange resin; iv) subjecting the process stream to at least one nanofiltration; v) subjecting the process to at least one electrodialysis; vi) treating the process stream at least one time with activated charcoal; and/or vii) subjecting the process stream at least one time to a crystallization (at least p. 19 lines 9-35), where the nanofiltration membrane has a molecular weight cut-off in the range 100-1000 Daltons (paragraph 0051) and therefore includes a molecular weight cut-off >300 Da. EP ‘067 discloses that the purified aqueous solution contains the at least one HMO or mixture of HMOs in a purity of at least 80% with respect to the weight of dry matter/solutes within the solution (paragraph 0078).
MPEP 2144.04 notes that a change in sequence of performing a step and/or ingredient is obvious. In this instance, it would have been obvious to one of ordinary skill before the effective filing date of the claimed invention to perform nanofiltration treatment before the cationic exchange resin treatment because doing so would still result in a concentrated and further purified oligosaccharide solution (instant claim 84). Additionally, since EP ‘067 discloses a method for purifying an oligosaccharide solution from a fermentation broth comprising the same components recited and further comprising the same steps and features recited to purify an oligosaccharide solution, EP ‘067 can be deemed to disclose that the oligosaccharides have the initial recited purities in the fermentation broth and the separated or purified oligosaccharides from the fermentation broth are a purity of >80% on total dry solid. Therefore, EP ‘067 can be deemed to render obvious the method of instant claims 84, 93-94, 95-97, 98-101, 102-103, 105-109, 111, 112-113, 119, 129, 143-144.
Regarding instant claim 85, 104, 112, EP ‘067 discloses at least one ultrafiltration treatment (p. 19 line 28). Therefore, it would be obvious that EP ‘067 discloses that an additional or second ultrafiltration treatment (or additional concentration step) can be performed before additional processing steps including the nanofiltration treatment and cationic exchange resin treatment. Further, EP ‘067 discloses that ultrafiltration membranes are suitable filtration methods to separate the cells from the fermentation broth; in ultrafiltration, cells, suspended solids and solutes of higher molecular are retained in the so-called retentate, while lower molecular solutes pass through the membrane in the permeate (filtrate); and ultrafiltration membranes are defined by their MWCO (paragraphs 0039-0042). Therefore, it would be obvious that when an additional ultrafiltration treatment is performed, the ultrafiltration membrane MWCO of the first ultrafiltration treatment is higher than that of the additional or second ultrafiltration treatment.
Regarding instant claims 86, 94, 117, 119, 146, EP ‘067 discloses a step vi) treating the process stream at least one time with activated charcoal, where the activated charcoal removes contaminating substances such as colorants from the process stream (paragraph 0062). EP ‘067 discloses that the purified aqueous solution contains the at least one HMO or mixture of HMOs in a purity of at least 80% with respect to the weight of dry matter/solutes within the solution (paragraph 0078). Since EP ‘067 discloses treating the oligosaccharide solution with the same treatment steps recited, EP ‘067 can be deemed to disclose an ash content of <10% on total dry solid.
Regarding instant claims 87-91, EP ‘067 discloses the at least one HMO or mixture of HMOs are produced by microbial fermentation by cultivating a genetically-engineered microorganism that is able to synthesize an HMO in a culture medium (fermentation broth) (paragraph 0038).
Regarding instant claim 92, EP ‘067 discloses the cell culture medium contains salts, including phosphate, and a glucose (carbon source) (p. 14-16 examples, specifically examples 3-4).
Regarding instant claims 95-97, 101, EP ‘067 discloses that the oligosaccharide solution comprises a mixture of HMOS, including at least two or more different HMOs, where the mixture of HMOs contain at least one neutral and/or at least one acidic HMO (paragraphs 0019-0023).
Regarding instant claims 100, 113, EP ‘067 discloses a further diafiltration after nanofiltration to concentrate the HMOs (paragraphs 0050-0053).
Regarding instant claims 109-110, EP ‘067 discloses a strong cationic exchange resin treatment and the eluent is set to pH 7.0 (paragraphs 0112, 0122).
Regarding instant claim 111, EP ‘067 discloses an electrodialysis step to separate and concentrate the ions in solution and purify the HMOs (paragraphs 0054-0056).
Regarding instant claim 112, EP ‘’067 discloses that the method for purifying the oligosaccharide solution comprises at least one of each treatment step as noted above. Therefore, it would be obvious that each of the steps in the purification process can be repeated at least one time during the purification process.
Regarding instant claim 115, 119, EP ‘067 discloses a further sterile filtration and/or endotoxin removal by filtration (paragraph 0064).
Regarding instant claim 116, EP ‘067 discloses enzymatic treatment to produce the desired oligosaccharides, such as adding a beta-galactosidase to the fermentation broth (paragraph 0121).
Regarding instant claims 120-121, EP ‘067 discloses the mixture of HMOs are produced by culturing a genetically modified E. coli, including a E. coli of Lacy+ (see examples, specifically examples 3-4).
Regarding instant claims 122, 125-127, EP ‘067 discloses the aqueous solution comprising the HMO mixture is spray-dried (paragraphs 0073, 0081-0093).
Regarding instant claims 123-124, EP ‘067 discloses a further step of concentrating the at least one HMO in the process stream, by vacuum evaporation, reverse osmosis or nanofiltration (paragraph 0065) or crystallized (paragraphs 0063, 0065), where the resulting process stream is an aqueous solution containing the HMOs in a concentration >100 g/l or even >300 g/l (paragraph 0066). Since EP ‘067 discloses a method for purifying a solution containing HMOs from a fermentation broth comprising the same components recited and further comprising the same steps and features recited to purify the oligosaccharides, where the HMOs are further concentrated by vacuum evaporation, reverse osmosis or nanofiltration, or crystallized, and spray-dried, it would be obvious to arrive at the recited conditions for concentrating the purified/isolated oligosaccharides by vacuum evaporation, reverse osmosis or nanofiltration by routine optimization and the recited conditions for crystallizing the purified/isolated oligosaccharides by routine optimization.
Regarding instant claims 114, 119, 129, 139, EP ‘067 discloses that the process for the purification of the at least one HMO is also advantageous in that the aqueous solution is free of genetically-engineered microorganisms and nucleic acid molecules derived from genetically-engineered microorganisms; in addition, the aqueous solution is free of proteins; the total removal of proteins eliminates the risk of causing allergies to a potential consumer (paragraph 0072). EP ‘067 discloses that the purified aqueous solution contains the at least one HMO or mixture of HMOs in a purity of at least 80% with respect to the weight of dry matter/solutes within the solution (paragraph 0078). Since EP ‘067 discloses a method for purifying a solution containing HMOs from a fermentation broth comprising the same components recited and further comprising the same steps and features recited to purify the oligosaccharides, EP ‘067 can be deemed to disclose that the HMOs have the initial recited purities in the fermentation broth and the separated or purified oligosaccharides from the fermentation broth are a purity of >80% being free of recombinant DNA and protein materials, having the recited Brix values, and having the recited conductivity.
Regarding instant claim 141, EP ‘067 discloses incorporating the spray-dried powder consisting essentially of structurally distinct HMOs into a food composition (paragraph 0090).
Regarding instant claim 145, EP ‘067 discloses that the electrodialysis is an alternative step (paragraph 0054). Therefore, it would be obvious that the purification process of a solution containing a mixture of HMOs of EP ‘067 does not have to comprise an electrodialysis treatment.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that EP ‘067 discloses nanofiltration and/or diafiltration as optional purification steps. Applicants assert that EP ‘067 does not expressly disclose that the nanofiltration membrane has a MWCO of > 300 Da, nor does it identify any lower bound on MWCO corresponding to the claimed limitation. Applicants assert that EP ‘067 teaches away from Applicants’ claimed architecture by presenting ion exchange as a selectable combination of cation and anion exchangers, rather than as a cation-only system that affirmatively excludes anionic ion exchange.
Applicants’ remarks are not persuasive. As noted above, instant claim 84 is essentially drawn to a method for purifying an oligosaccharide solution from a cultivation or fermentation broth obtained by cell cultivation or microbial fermentation, the method steps comprising i) clarifying the cultivation or fermentation broth; ii) nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that does not include anionic ion exchange, wherein a purified oligosaccharide solution at a purity of > 80% on total dry solid is obtained.
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). MPEP 2123.
In this instance, EP ‘067 discloses a process for purifying an aqueous solution containing at least one HMO from a fermentation broth obtained from cell cultivation or microbial fermentation, comprising i) removing the microbial cells from the fermentation broth to obtain a process stream; ii) subjecting the process stream to at least one ultrafiltration; iii) treating the process stream to at least one time with a cation exchange resin; iv) subjecting the process stream to at least one nanofiltration; v) subjecting the process to at least one electrodialysis; vi) treating the process stream at least one time with activated charcoal; and/or vii) subjecting the process stream at least one time to a crystallization (at least p. 19 lines 9-35), where the nanofiltration membrane has a molecular weight cut-off in the range 100-1000 Daltons (paragraph 0051) and therefore includes a molecular weight cut-off >300 Da. EP ‘067 discloses that the purified aqueous solution contains the at least one HMO or mixture of HMOs in a purity of at least 80% with respect to the weight of dry matter/solutes within the solution (paragraph 0078).
Since EP ‘067 discloses that the purification comprises one or more of the steps (i) to (vii), EP ‘067 fairly discloses a method for purifying an oligosaccharide solution obtained from microbial fermentation as recited in instant claim 84 and comprising the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange.
Regarding Applicants’ remarks that EP ‘067 does not expressly disclose that the nanofiltration membrane has a MWCO of > 300 Da, nor does it identify any lower bound on MWCO corresponding to the claimed limitation, the remarks are not persuasive. As noted above, EP ‘067 discloses that the nanofiltration membrane has a molecular weight cut-off in the range 100-1000 Daltons (paragraph 0051); therefore, nanofiltration membrane MWCO of EP ‘067 includes the recited MWCO of > 300 Da.
Regarding Applicants’ remarks that EP ‘067 teaches away from Applicants’ claimed architecture by presenting ion exchange as a selectable combination of cation and anion exchangers, rather than as a cation-only system that affirmatively excludes anion exchange, the remarks are not persuasive. In this instance, EP ‘067 expressly discloses that treatment with a cation exchange resin is an alternative to an anion exchange resin (at least p. 19 lines 29-30).
Therefore, EP ‘067 discloses a method for purifying an oligosaccharide solution obtained from microbial fermentation as recited in instant claim 84 and comprising the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange.
Applicants assert that moreover, EP ‘067 provides not teaching or suggestion that would motivate one of ordinary skill to modify its disclosed purification scheme to exclude anion exchange or dialysis.
Applicants’ remarks are not persuasive. As already noted above, EP ‘067 expressly discloses that treatment with a cation exchange resin is an alternative to an anion exchange resin (at least p. 19 lines 29-30), and therefore, EP ‘067 can fairly be deemed to disclose excluding an anion exchange.
Regarding Applicants’ remarks on the exclusion of dialysis, the remarks are not persuasive because instant claim 84 does not exclude a dialysis step.
While dependent instant claim 145 does recite excluding a dialysis step, it would have been obvious to do so because EP ‘067 discloses that the electrodialysis is an alternative step (paragraph 0054). Therefore, it would be obvious that the purification process of a solution containing a mixture of HMOs of EP ‘067 does not have to comprise an electrodialysis treatment.
Applicants assert that dependent claim 85 further recites a specific purification scheme order, namely that concentrating occurs before the salt and/or medium component removal step. Applicants assert that EP ‘067 does not merely omit this ordering, but instead conditions nanofiltration on prior ion-exchange and filtration, such that reversing the order would not be straightforward or suggested modification.
Applicants’ remarks are not persuasive. As noted above, EP ‘067 discloses a method for purifying an oligosaccharide solution obtained from microbial fermentation as recited in instant claim 84 and comprising the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange. MPEP 2144.04 notes that a change in sequence of performing a step and/or ingredient is obvious. In this instance, it would have been obvious to one of ordinary skill before the effective filing date of the claimed invention to perform nanofiltration treatment before the cationic exchange resin treatment because doing so would still result in a concentrated and further purified oligosaccharide solution (instant claim 84). Additionally, EP ‘067 discloses at least one ultrafiltration treatment (p. 19 line 28). Therefore, it would be obvious that EP ‘067 discloses that an additional or second ultrafiltration treatment (or additional concentration step) can be performed before additional processing steps including the nanofiltration treatment and cationic exchange resin treatment (instant claim 85).
Applicants assert that dependent claim 108 imposes an additional structural limitation requiring that the MWCO of the nanofiltration membrane is lower than the MWCO of the ultrafiltration membrane. Applicants assert that although EP ‘067 discloses both ultrafiltration and nanofiltration, it does not disclose this comparative MWCO relationship as a defined architectural requirement.
Applicants’ remarks are not persuasive. EP ‘067 discloses ultrafiltration membranes are defined by the MWCO of the membrane used and discloses examples including a 6 kDa filter (at least p. 16 lines 1-2, lines 52-53). As already noted, EP ‘067 discloses that the nanofiltration membrane has a molecular weight cut-off in the range 100-1000 Daltons (paragraph 0051). Therefore, it would be obvious to one of ordinary skill that EP ‘067 discloses that the MWCO of the nanofiltration membrane is lower than that of the ultrafiltration membrane.
Applicants assert that dependent claim 145 further requires that step ii) does not comprise electrodialysis. Applicants assert that EP ‘067 expressly includes electrodialysis as a purification option and does not teach or suggest the claimed process architecture that affirmatively excludes electrodialysis.
Applicants’ remarks are not persuasive. As noted above, while dependent instant claim 145 does recite excluding a dialysis step, it would have been obvious to exclude a dialysis step because EP ‘067 discloses that the electrodialysis is an alternative step (paragraph 0054). Therefore, it would be obvious that the purification process of a solution containing a mixture of HMOs of EP ‘067 does not have to comprise an electrodialysis treatment in the method for purifying an oligosaccharide solution obtained from microbial fermentation as recited in instant claim 84 and comprising the same recited combination of nanofiltration with a molecular weight cut-off > 300 Da together with a cationic ion-exchange treatment that expressly excludes anionic ion exchange noted above.
For at least these reasons, the 103 rejection is maintained.
No claim is allowed.
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 Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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, Manjunath N. Rao can be reached at 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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/Marsha Tsay/Primary Examiner, Art Unit 1656
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