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
The amendment filed 12/11/2025 has been entered. Claims 3-5 and 12-14 are cancelled. Claims 1, 2, 6-11, and 15-20 are pending and under examination.
Response to Arguments
With respect to the rejections of claims 2 and 15-20 under 35 USC 112(b), and of claims 1, 2, 6-10, 15-18, and 20 under 35 USC 103, Applicant's arguments filed 12/11/2025 have been fully considered but they are not persuasive.
Applicant argues that claim 2 has been amended so that the phrase “gene expression inducer” is further defined and that the amendment overcomes the rejection under 35 USC 112(b). However, the amended claim language is still unclear if “gene expression inducer” and “allolactose” are equivalent terms.
Regarding the rejection under 35 USC 103, Applicant argues that Huber teaches away from using added glucose as the claimed high lactose concentrations and bases the argument on two sentences of Huber found on p. 1998, col. 2, Transgalactosylase Activity with Glucose as Acceptor. The two sentences on p. 1998 of Huber state: “At low initial lactose concentrations there was a significant increase in allolactose production when -no glucose was present. At high initial lactose concentrations (>0.10 M), the allolactose production did not increase over normal”. Huber does not disclose whether or not glucose was present or a specific glucose concentration at the lactose concentrations of >0.10 M. Huber does not report any data showing the exact allolactose concentrations at differing glucose and lactose concentrations. Huber is silent as to whether or not increasing glucose concentrations may have an effect on allolactose production, and does not teach away from optimizing glucose concentrations.
Therefore, Applicant’s arguments are not persuasive.
Claim Rejections - 35 USC § 112(b)
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.
Claims 2 and 15-20 are 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 2 recites a method for producing a gene expression inducer comprising allolactose, but none of the active method steps recite a gene expression inducer. The claim only recites method steps for producing allolactose. It is unclear whether “allolactose” is an equivalent claim term to a “gene expression inducer”, or if the gene expression inducer comprises an additional component other than allolactose. Claims 15-20 are also rejected as they depend from claim 2.
Claim Rejections - 35 USC § 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 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.
Claims 1, 2, 6-10, 15-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Huber et al. ("A Quantitation of the Factors Which Affect the Hydrolase and Transgalactosylase Activities of β-Galactosidase (E. coli) on Lactose" BIOCHEMISTRY 1976, Vol. 15, No. 9), in view of Nakamura et al., (U.S. Pub. No. 2016/0251689 A1), previously cited.
It is interpreted that a lactose concentration of 120 g/L or more combined with a glucose/galactose concentration of 120 g/L or more is equal to 1 Eq/L or more.
Regarding claims 1 and 2, Huber teaches a method of producing allolactose, which is the “natural inducer” of the lac operon (Page 1994, Column 2, Paragraph 1), by incubating β-galactosidase from E. coli with lactose (Abstract). Although Huber does not explicitly teach that the reaction mixture containing allolactose was collected, Huber does teach that allolactose was a product of the reaction (Figure 1), therefore, one of ordinary skill in the art would be reasonably expected to understand that said allolactose could have been collected based on the teachings of Huber. Huber teaches a concentration of 0.5 M lactose (Page 1995, Column 2, Results), which is equivalent to approximately 171 g/L lactose, as the molecular weight of lactose is 342.3 g/mol. Huber teaches that studies were carried out by adding 0.5 M glucose to a spectrum of lactose concentrations (Page 1998, Column 2, Paragraph 3, Transgalactosylase Activity with Glucose as Acceptor). 0.5 M glucose is equivalent to approximately 90 g/L glucose, as the molecular weight of glucose is 180.156 g/mol.
Although the glucose concentration taught by Huber differs from the glucose concentration of the instant claims, MPEP§ 2144.05 II states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")” The selection of specific glucose concentrations would have been a routine matter of optimization on the part of the artisan of ordinary skill, said artisan recognizing that glucose concentrations would affect enzyme product formation.
Huber does not teach ipsis verbis that the β-galactosidase is expressed by a microorganism, i.e., Huber does not teach an in vivo reaction, although Huber teaches highly purified beta-galactosidase from E. coli K-12 (p. 1994, Column 2, second passage under Experimental Section).
However, Nakamura teaches a modified β-galactosidase, a gene encoding said β-galactosidase, and a microorganism carrying said gene (Claims 22-25), i.e., Nakamura teaches a microorganism expressing a β-galactosidase enzyme. Nakamura does not mention subjecting cells to a treatment for increasing membrane permeability.
It would have been obvious to one or ordinary skill in the art, prior to the effective filing date of the claimed invention, to have contacted a microorganism expressing β-galactosidase, as taught by Nakamura, with lactose and glucose to generate allolactose, as taught by Huber. One of ordinary skill in the art would have been motivated to do so because Nakamura teaches that certain β-galactosidase variants of the invention produced increased allolactose compared to wild type (para. [0225]; Figure 5B). One of ordinary skill in the art would have had a reasonable expectation of success as Huber and Nakamura are in the same field of endeavor of β-galactosidase studies.
Regarding claims 6 and 20, as stated, Huber teaches a glucose concentration that is equivalent to approximately 90 g/L. Although the concentration of Huber differs from that of the instant claim, generally differences in concentration and temperature will not affect patentability. See MPEP§ 2144.05 II, stated above.
Regarding claims 7 and 15, Huber teaches that the enzyme/substrate mixture, i.e., the reaction mixture, was incubated at a temperature of 30˚C or 0˚C (Page 1, Column 1, Paragraph 1).
Regarding claims 8 and 16, Nakamura does not mention that the cells were subjected to drying treatment, freeze-thaw treatment, surfactant treatment, or organic solvent treatment.
Regarding claims 9 and 17, Huber teaches highly purified beta-galactosidase from E. coli K-12 (p. 1994, Column 2, second passage under Experimental Section) and Nakamura teaches that the microorganism transformed with the recombinant β-galactosidase was E. coli (Page 3, Figure 2).
Regarding claims 10 and 18, as stated, Nakamura teaches that certain β-galactosidase variants of the invention produced increased allolactose compared to wild type (para. [0225]; Figure 5B).
Claims 11 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Huber et al., 1976 (A Quantitation of the Factors Which Affect the Hydrolase and Transgalactosylase Activities of β-Galactosidase (E. coli) on Lactose) and Nakamura et al., (U.S. Pub. No. 2016/0251689 A1), as applied to claims 1 and 2 above, and further in view of UniProt ID A0A024L722_ECOLX, integrated into UniProt 07/09/2014.
As stated above, Huber teaches a method of producing allolactose in the presence of glucose and lactose, while Nakamura teaches expression of a β-galactosidase in E. coli cells that have not been subject to a treatment for increasing membrane permeability.
Huber and Nakamura do not teach a sequence with 100% sequence identity to instant SEQ ID NO:16.
However, regarding claims 11 and 19, UniProt ID A0A024L722_ECOLX teaches a seqeucne with 100% sequence identity to instant SEQ ID NO:16 (see alignment attached to this Office action).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have used Escherichia coli to express a β-galactosidase, as taught by Nakamura, comprising the amino acid sequence of UniProt ID A0A024L722_ECOLX, in the presence of glucose and lactose, as taught by Huber. One of ordinary skill in the art would have been motivated to do so because Huber teaches that a β-galactosidase from E. coli produces allolactose in the presence of glucose and lactose (Abstract; Page 5, Column 2, Paragraph 3, Transgalactosylase Activity with Glucose as Acceptor).
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 RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 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, Louise Humphrey can be reached at (571) 272-5543. 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.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657