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 .
Claims 25-34 and 38-45 are pending and are under examination.
Information Disclosure Statement
The information disclosure statement filed 3/29/2024 has been considered and initialed copies are enclosed.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
The name of the size of the ASCII text file should be in bytes instead of kB as set forth in the 2nd paragraph of the specification.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because of the implied language in the abstract which is “the present disclosure contemplates”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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.
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.
Claim(s) 25, 33-34 and 42-45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lombo et al. WO 2016185057 11-24-2016 cited in IDS in view of Kim et al. KR20180099380A 9-5-2018.
Lombo et al discloses a bacterium containing a stable plasmid/ stable expression vector pLMF56 whose sequence is SEQ ID NO: 62 (figure 12) for producing equol, wherein the plasmid comprises 4 genes involved in its synthesis wherein the genes are:
(DZNR) (SEQ ID NO. 51),
(DHDR) (SEQ ID NO: 54),
(THDR) ( SEQ ID NO: 57), and
the dihydrodaidzein racemase (SEQ ID NO: 60).
These genes were synthesized by optimizing the codons (SEQ ID NO: 52. SEQ ID NO: 55, SEQ ID NO: 58 and SEQ ID NO: 61, respectively).
Lombo et al disclose: The expression vector (“the term "expression vector", as used herein, refers to a cloning vector suitable for expressing a nucleic acid that has been cloned therein after being introduced into a cell, called a host cell”) is comprised in a cell such as Escherichia.
“The term 'host cell' or 'host cell' or 'transformed cell' includes any cultivable cell that can be modified by introducing the nucleic acid of the invention, the cassette of the invention, the vector of the invention, or the protein The transformed cell of the invention may have the nucleic acid of the first aspect of the invention or the gene construct cloned into a gene vector capable of replicating stably in said cell, such as in a plasmid, or the vector of the second aspect of the invention.")
Lombo et al disclose the use of the bacterium from genus E. coli as a medicament for the treatment of cardiovascular disease in a human.
“Another aspect of the present invention relates to the use of the nucleic acid of the first aspect of the invention, the expression cassette of the second aspect of the invention, the vector of the third aspect of the invention, the fusion protein of the fourth aspect of the invention and / or the cell of the fifth aspect of the invention as a medicament, that is, for the preparation of a medicament. Preferably for the treatment or prevention of (or for the preparation of a medicament for the treatment and / or prevention or for its use in the treatment or prevention) of diseases in which the polyphenols described in the present invention alleviate the symptoms, cure or mitigate the disease; said diseases can be any of those known to those skilled in the art in which the action of the polyphenols described herein improves the health status of the individual. For example they can be used to prevent and treat tumors, cardiovascular disease”. "The composition of this invention can be administered by any appropriate route of administration, for which said composition will be formulated in the pharmaceutical form appropriate to the route of administration chosen.")
Regarding claims 42-43, Lombo et al disclose the use of plasmid with ampicillin resistance as a means of selection for bacteria comprising the cloned genes. See table 4 p. 58-59.
Claim 44-45: Lombo et al disclose the E. coli can be administered orally via liquid or food stuff. "Therefore the present invention also relates to the use of the cell of the fifth aspect of the invention (non-pathogenic) for the production of a food, a fermented milk product, dietary supplement or an edible probiotic product."
Thus, Lombo et al disclose a method for modifying the phenotype of a mammalian gut comprising introducing to the mammalian gut the probiotic E. coli for the treatment of cardiovascular disease.
Lombo et al does not disclose the Escherichia contains at least two stable plasmids for isoflavone metabolism, said plasmids providing one or more components of isoflavone metabolism for converting Daidzein to Equol, Genistein to 5-Hydroxy- Equol, or both. Lombo et al does not disclose the probiotic comprises a first bacterium having a first plasmid comprising the nucleotide sequence or sequences encoding DZNR, DDRC or both; and a second bacterium having a second plasmid comprising the nucleotide sequence or sequences encoding DHDR, THDR or both.
Kim et al disclose the use of two recombinant E. coli for producing equol, wherein the first recombinant E.coli comprises a plasmid comprising nucleotide sequence or sequences encoding both DZNR and DDRC; and a second bacterium having a second plasmid comprising the nucleotide sequence or sequences encoding both DHDR and THDR. See title and figure 4. “A recombinant Escherichia coli expressing a daidzein reductase and a dihydrodiadase as a single vector, and a recombinant Escherichia coli expressing a reductase which is a dihydroidide, a reductase, a tetrahydrodide, as a single vector”.
Kim et al disclose according to fig. 4, the recombinant Escherichia coli 1 converts genistein to (S) -dihydrogenentanthine and the (S) -dihydrogenentanthin is converted to 5-hydroxy- (S) equol, indicating that selective recombination of 5-hydroxy-equol from genistein by recombinant E. coli 1 and 2 is possible. The whole cell reaction system in which the reaction is compartmentalized with different recombinant E. coli is advantageous in that the productivity and final yield of 5-hydroxy- (S) -equol is improved and the production of 5-hydroxy-dihydroequ - (S) -equol is increased by reducing the selectivity to 5-hydroxy- (S) -equol. The selective synthesis of the 5-hydroxy-equol can selectively synthesize 5-hydroxy- (S) -equol. Specifically, 5-hydroxy- (S) -equol can be selectively synthesized using recombinant Escherichia coli overexpressing 5-fold or more of a tetrahydrodaidzein reductase, or recombinant Escherichia coli 1 and 2 have.
Kim et al disclose that using this partitioned reaction system with E. coli 1 and E. coli 2, the conversion of substrate genistein to 5-hydroxy-equol was 99% or more and production of 5-hydroxy-equol increased 1.6 fold as compared to when all 4 enzymes were expressed in one E. coli cell. Kim et al also disclose that in the partitioned reaction system, the expression of all 4 enzymes were increased as compared to when all 4 enzymes were expressed in one E. coli. See under example 3.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have modified the method of Lombo et al as taught by Kim et al such that there are two of the E. coli in the probiotic, wherein the first E. coli comprises a first stable plasmid comprising the nucleotide sequences encoding both DZNR and DDRC; and the second E. coli having a second stable plasmid comprising the nucleotide sequences encoding both DHDR and THDR, as taught by Kim et al, thus resulting in the instant invention with a reasonable expectation of success.
The motivation to do so is that using this partitioned reaction system with the first and second recombinant E. coli, the conversion of substrate genistein to 5-hydroxy-equol was 99% or more and production of 5-hydroxy-equol increased 1.6 fold as compared to when all 4 enzymes were expressed in one E. coli cell. Kim et al also disclose that in the partitioned reaction system, the expression of all 4 enzymes were increased as compared to when all 4 enzymes were expressed in one E. coli.
The ratio of the first bacterium to the second bacterium as disclosed in claim 34 is a result effective variable and the ratios would have been achieved by routine optimization and thus have been prima facia obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention based on example 3 of Kim et al disclosing the selective synthesis of 5-hydroxy-equol from genistein substrate using the partitioned reaction system with the first recombinant E.coli comprises a plasmid comprising nucleotide sequence or sequences encoding both DZNR and DDRC; and a second bacterium having a second plasmid comprising the nucleotide sequence or sequences encoding both DHDR and THDR.
Regarding claims 42-43, the presence of an Ampicillin resistance gene in both plasmids would act as a means for selection of the E. coli expressing the cloned enzymes as taught by Lombo et al.
Claim(s) 26-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lombo et al. WO 2016185057 11-24-2016 cited in IDS and Kim et al. KR20180099380A 9-5-2018 as applied to claims 25, 33-34 and 42-45, further in view of Wang et al. Progress in Polymer Science, vol. 60, September 2016, pages 18-50.
The combination of Lombo et al and Kim et al does not disclose further co-administering a transduction agent such as a polycation.
Wang et al disclose that polycations are useful delivery vehicles for nucleic acids and proteins. See title, abstract and generally the whole reference.
Since Lombo et al disclose that the vectors encoding the enzymes for production equol and 5-hydroxy-equol can be administered to treat cardiovascular disease.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have further administered the plasmids encoding the enzymes as well as a transduction agent such as polycations which would act as a delivery vehicle for the plasmids as taught by Wang et al.
Claim(s) 28-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lombo et al. WO 2016185057 11-24-2016 cited in IDS and Kim et al. KR20180099380A 9-5-2018 as applied to claims 25, 33-34 and 42-45 above, further in view of Wang et al. US 2020/0147155 5/14/2020.
The combination of Lombo et al and Kim et al does not disclose introducing the probiotic to the mammalian gut is performed according to a dosage regimen.
Wang et al discloses dosing regimens for probiotic bacteria (abstract - "Disclosed herein are methods and compositions related to probiotic formulas. These compositions can be used in a variety of methods to treat and/or ameliorate diseases, such as colonization of antibiotic- resistant bacteria in the host organism. Also disclosed herein are methods of treating those subjects in need thereof by administering the compositions disclosed herein"; para [0088] "The composition comprising Lactobacillus crispatus WZ-12 or a derivative thereof can comprise Lactobacillus crispatus WZ-12 or a derivative thereof in an amount from 1x10^4 to 1x10^7 colony forming units per milliliter. For example, the amount can be 1x10^4, 1x10^5, 1x10^6, or 1x10^7, or any amount in between, above, or below."; para [0102] - "The compositions disclosed herein can be used to modulate gut microflora in a variety of ways, which can be customized to the subject receiving the treatment. For example, the treatment can occur in 2, 3, 4, 5, 6, 7, or more doses. The doses can be given once every day, or can be administered multiple times throughout the same day."), and where a probiotic may be E. coli (para [0064] - "Also disclosed herein is a probiotic composition comprising the E. coli strain M9-4-1.").
Since the combination of Lombo et al and Kim et al discloses administering probiotic compositions comprising bacteria and Wang et al discloses dosing regimens for probiotic compositions comprising bacteria, it would have been prima facie obvious to one of ordinary skill in the art as of the effective filing date to modify the method of the combination of Lombo et al Kim et al, to use a dosing regimen, such as administering 1x10^4 - 1x10^7 CFU/mL once a day for multiple doses, as taught by Wang et al (see below), thus resulting in the instant invention with a reasonable expectation of success
Regarding claim 29, Wang et al further discloses wherein the dosage regimen comprises: introducing the probiotic having a concentration of the bacterium to the mammalian gut at a dosing schedule over the course of a time period (para [0102]).
Regarding claim 30, Wang further discloses wherein the concentration is between 1x10^6 to 1x10^10 CFU/mL (para [0088]).
Regarding claim 31, Wang et al further discloses wherein the time period is selected from: every 4 hours, every 6 hours, every 12 hours, every 24 hours, or every 48 hours (para [0102]).
Regarding claim 32, Wang et al further discloses wherein the time period is 1 day, 1 week, 1 month, or one year (para [0102]).
Allowable Subject Matter
Claims 38-41 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Status of Claims
Claims 38-41 are objected to. Claims 25-34 and 42-45 are rejected.
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/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645