DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-13 are pending and under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement has been considered with the exception of the lined through foreign patents not in the English language. The lined through references have not been considered because the disclosure statement fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
Claims 1 and 10-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification lacks complete deposit information for the deposit of Escherichia coli strain No. 13-XA at paragraph [0008] of the specification. Because it is not clear that bacterial cell lines possessing the properties of the 13-XA strain are known and publicly available or can be reproducibly isolated from nature without undue experimentation and because the best mode disclosed by the specification requires the use of Escherichia coli strain No. 13-XA, a suitable deposit for patent purposes is required. Accordingly, filing of evidence of the reproducible production of the cell line claimed in claim 1, is required. Without a publicly available deposit of the above bacterial cell line, one of ordinary skill in the art could not be assured of the ability to practice the invention as claimed. Exact replication of the cell line is an unpredictable event.
Applicant's referral to the deposit of the Escherichia coli strain at paragraph [0008] of the specification is an insufficient assurance that all required deposits have been made and all the conditions of 37 CFR §1.801-1.809 have been met.
If the deposit has been made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty, that all restrictions upon public access to the deposit will be irrevocably removed upon the grant of a patent on this application and that the deposit will be replaced if viable samples cannot be dispensed by the depository is required. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State. Amendment of the specification to recite the date of deposit and the complete name and full street address of the depository is required.
If the deposits have not been made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR §1.801-1.809, assurances regarding availability and permanency of deposits are required. Such assurance may be in the form of an affidavit or declaration by applicants or assignees or in the form of a statement by an attorney of record who has the authority and control over the conditions of deposit over his or her signature and registration number averring:
(a) during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request;
(b) all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application;
(c) the deposits will be maintained in a public depository for a period of at least thirty years from the date of deposit or for the enforceable life of the patent of or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest; and
(d) the deposits will be replaced if they should become nonviable or non-replicable.
In addition, a deposit of biological material that is capable of self-replication either directly or indirectly must be viable at the time of deposit and during the term of deposit. Viability may be tested by the depository. The test must conclude only that the deposited material is capable of reproduction. A viability statement for each deposit of a biological material not made under the Budapest Treaty must be filed in the application and must contain:
1) The name and address of the depository;
2) The name and address of the depositor;
3) The date of deposit;
4) The identity of the deposit and the accession number given by the depository;
5) The date of the viability test;
6) The procedures used to obtain a sample if the test is not done by the depository; and
7) A statement that the deposit is capable of reproduction.
As a possible means for completing the record, applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit.
If the deposit was made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the hybridoma cell line described in the specification as filed is the same as that deposited in the depository. Corroboration may take the form of a showing of a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant's possession at the time the application was filed. Applicant's attention is directed to In re Lundack, 773 F.2d. 1216, 227 USPQ 90 (CAFC 1985) and 37 CFR §1.801-1.809 for further information concerning deposit practice.
Claims 2-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims require the use of a specific mutant E. coli ST11 to make the E. coli ST 13-XA strain neither of which are not apparently publicly available. The mutant E. coli ST11 strain material is required for the production of the E. coli strain designated as 13-XA. The claims reference another patent application for the method to produce the mutant E. coli ST11 strain, however, the methods of making that strain is not readily apparent merely from the recited genotype. It is the exact mutant E. coli ST11 strain that is required, and its public availability is deemed “essential material” to practice the method of making the E. coli ST 13-XA strain. The reference to another patent application is improper and cannot support a description of the recited mutant E. coli ST11. Neither the claims nor the specification provides for a proper statement of specific incorporation by reference to the patent application. As set forth in 37 CFR 1.57 (c) …”(c) Except as provided in paragraphs (a) or (b) of this section, an incorporation by reference must be set forth in the specification and must: (1) Express a clear intent to incorporate by reference by using the root words "incorporat(e)" and "reference" ( e.g. , "incorporate by reference"); and (2) Clearly identify the referenced patent, application, or publication.” Here, neither 37 CFR 1.57(a) or (b) are relevant because the patent application referenced in claim 2 and the specification is not a prior filed application or priority application of the instant application. Absent the unrestricted public availability of the mutant E. coli ST11 strain the claims are not enabled. Applicant may consider depositing the strain according to the terms of the Budapest treaty to resolve this issue as set forth below. Applicant should note the particulars for a deposit that is made after the effective date for filing a Patent in the United States.
If the deposit has been made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty, that all restrictions upon public access to the deposit will be irrevocably removed upon the grant of a patent on this application and that the deposit will be replaced if viable samples cannot be dispensed by the depository is required. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State. Amendment of the specification to recite the date of deposit and the complete name and full street address of the depository is required.
If the deposits have not been made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR §1.801-1.809, assurances regarding availability and permanency of deposits are required. Such assurance may be in the form of an affidavit or declaration by applicants or assignees or in the form of a statement by an attorney of record who has the authority and control over the conditions of deposit over his or her signature and registration number averring:
(a) during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request;
(b) all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application;
(c) the deposits will be maintained in a public depository for a period of at least thirty years from the date of deposit or for the enforceable life of the patent of or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest; and
(d) the deposits will be replaced if they should become nonviable or non-replicable.
In addition, a deposit of biological material that is capable of self-replication either directly or indirectly must be viable at the time of deposit and during the term of deposit. Viability may be tested by the depository. The test must conclude only that the deposited material is capable of reproduction. A viability statement for each deposit of a biological material not made under the Budapest Treaty must be filed in the application and must contain:
1) The name and address of the depository;
2) The name and address of the depositor;
3) The date of deposit;
4) The identity of the deposit and the accession number given by the depository;
5) The date of the viability test;
6) The procedures used to obtain a sample if the test is not done by the depository; and
7) A statement that the deposit is capable of reproduction.
As a possible means for completing the record, applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit.
If the deposit was made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the hybridoma cell line described in the specification as filed is the same as that deposited in the depository. Corroboration may take the form of a showing of a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant's possession at the time the application was filed.
Applicant's attention is directed to In re Lundack, 773 F.2d. 1216, 227 USPQ 90 (CAFC 1985) and 37 CFR §1.801-1.809 for further information concerning deposit practice.
Claims 2-13 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claims 2-9, the claim recites E. coli ST11 and E. coli ST12, the abbreviation “STXX” is well known in the art to mean sequence type. Applicant should clarify if the “STXX” in the claim represents the strains having sequence type 11 or 12 or if the abbreviation represents a laboratory designation. Additionally, claim 2 (and dependent claims 3-9) provides reference to mutant ST11 strain disclosed in a patent which is an improper incorporation of essential material by reference and as such renders the scope of the claim indefinite. Claim 2 recites that the genotype of the mutant E. coli ST13 is ΔfadR which is not set forth in the method steps of the claim and lacks antecedent basis in the claim. Similarly, ΔPfadD::PCPA1 is also set forth in the claim but lacks clear antecedent basis in the prior method steps. Claim 2 merely states enhancing the promoter and not its replacement as set forth in the description of the mutant E. coli ST13 genotype in the method of making the ST13 strain. The genotypes of the strains do not match the method steps set forth and the method steps do not result in the particular genotype of E. coli strain S13T-XA as set forth in claim 1. As to claims 3-9, the do not provide for proper antecedent basis in the clear reference to method steps of the prior claims. For example, claim 4 which depends on claim 3 recites gene thrA, however the claim 3 recites thrA-1 and thrA-2, which one or both is referenced in the method. .Similarly, what specifically is claim 4 limiting the gene sequence that the A-1 and A-2 are derived or the final insert. As to claim 5, it is unclear which specific method step(s) in claim 2 is being further limited and multiple elements such as “the pCas plasmid” lack clear antecedent basis in the prior claims. Dependent claims must properly further limit the method from which they depend on and provide for proper antecedent basis for the claim terms. The abbreviation “LB” is used without properly defining the acronym at its first usage. These dependent claims (3-9) do not meet the basic requirements. Finally, the claim provides for generic language that never completely identifies the steps required to make the specific strain of claim 1. The generic language never arrives as the specific genetic steps and elements in strain ST13-XA.
As to claims 10-13, the claims recite “use of” which is not a statutory category of invention in the use. Applicant should present the claims as “ A method of”…..with active method steps drafted in present tense. As to claim 10, the claim is indefinite in the recitation of the term “employed” as this does not provide for any method steps that result in the production of L-homoserine. It is unclear how the strain is employed in an unknown and undefined process.
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.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over CN114480233 (herein after ‘233; of record citations to google English translation) in view of CN102741420 (herein after ‘420; of record citations to google English translation), Zhang et al (Microbial Cell Factories, 18:130 pages 1-11, 2019) and WO 2018/188617 (herein after ‘617; of record citations to google English translation).
The ‘233 patent teaches the ST11-A E. coli base strain using the plasmid pRB1k to express thrA (S345F) and teaches the strain for high efficiency fermentation in the preparation of L-homoserine. The ST11-A strain is produced from the base ST11 strain having which is the starting base strain of the instant claims. The ST11-A strain is used for the production of L-homoserine and the culture conditions and media are set forth at example 4. The ‘233 patent teaches that those skilled in art can adjust the components according to actual situations and the fermentation medium may comprise components in amounts that are replaceable by any value within certain ranges. The ST11 E. coli mutant recited in the specification and the claims herein is identical to the ST11 base strain of the ‘233 patent. The ST11 strain is modified by placing the thrA (S345F) gene in plasmid pRB1k. The instant strain places the thrA (S345F) in plasmid pXB1k. Additionally, the ST11-A strain does not have fadR deleted and the promoter of the long-chain fatty acid coenzyme A ligase gene fadD enhanced by replacement with the PCPA1 promoter.
The ‘420 patent teaches additional desirable mutations for production of L-amino acids in media containing fatty acids or oil hydrolysates. The ‘420 patent teaches compared to traditional L-amino acid fermentation production method mainly using carbohydrates as a carbon source and using microorganisms, the present invention provides fatty acid or oil hydrolysate with microorganisms with high assimilation ability which is efficient and cheap L- amino acid production and that bacteria belonging to the Enterobacteriaceae family which have the ability to assimilate fatty acids can efficiently produce L-amino acids including E. coli. The ‘420 patent teaches deletion of the fadR gene provides for enhanced fatty acid assimilation (page 7, text before Example 1). The ‘420 patent also teaches enhancing the expression of one or more genes including fadD (page 2 of google translation) where enhancement can be by modifying the gene expression regulatory sequence by amplifying the activator that can increase the expression of the gene of the present invention or deleting or weaking the regulator that can reduce expression. The ‘420 generally teaches replacement includes replacing the promoter to enhance gene expression (page 7). The ‘420 patent does not teach replacing the fadD promoter with the CPA1 promoter to enhance expression.
Zhang et al teaches metabolic engineering of E. coli for efficient supply of acetyl-coA from different carbon sources. Zhang et al teach that when fatty acids were used as a carbon source acetyl-CoA was improved by deletion of fadR and constitutive expression of fadD under the strong promoter CPA1. Zhang et al teach various culture media for E. coli growth.
The ‘617 document teaches the expression vector in E. coli for expression of genes in E. coli. The expression vector may be a plasmid with pSB1s or pXB1k (SEQ ID NO:35). It is noted that SEQ ID NO:1 herein is 100% identical with SEQ ID NO:35.
It would have been prima facie obvious to one having skill in the art at the time the invention was made to make the E. coli ST11 strain ΔfadR and enhancing the fadD gene expression by substituting the fadD promoter with the strong promoter CPA1 (ΔPfadD::PCPA1) according to Zhang et al and ‘420 patent and then transform with the pXB1k having the thrA(S345F) gene inserted between the NcoI and EcoR1 restriction sites thereof, the pXB1k being functionally equivalent to the pRB1k of the ‘223 patent to arrive at the instantly claimed 13-XA strain. One would have been motivated to produce the modified strain to arrive at a modified strain that utilizes either carbohydrates or fatty acids/oil hydrolysates for the production of L-amino acids and L-homoserine in particular. It would have been prima facie obvious to modify the culture conditions to optimize the production of L-homoserine as the ‘233 patent teaches such is desirable and each of the ‘240, Zhang et al and ‘617 teach modifications of E. coli to promote the production of amino acids having desirable properties and that the ‘240 and Zhang et al teach culture conditions for both carbohydrate and fatty acid substrates for the modified E. coli and it is routine in the art to optimize the culture conditions for the desired endproduct, L-homoserine. As such, given the art as a whole, the E. coli ST13-XA, its method of making and method of using is prima facie obvious over the art.
Status of Claims
Claims 1-13 stand rejected.
Conclusion
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/Patricia Duffy/Primary Examiner, Art Unit 1645
