DETAILED ACTION
Status of Application
Claims 1-20 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of Group I, claims 1-17, drawn to a method for yielding an azacyclic α-amino acid, comprising: providing a Mannich cyclase in a solution; and contacting a substrate, and Applicant’s species election without traverse of Substrate A, as submitted in communication filed on 06/24/2026 is acknowledged.
In view of the election of substrate A, claims 11-16 are not directed to the elected invention. Claims 11-16 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/24/2026.
Claims 1-10 and 17, are at issue and will be examined to the extent they encompass the elected invention.
Priority
Acknowledgment is made of applicant’s claim for domestic priority under 35
U.S.C. 119 (e) to provisional Application No. 63/512236 filed on 07/06/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/13/2026
is acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 07/08/2024 have been reviewed and are accepted by
the examiner for examination purposes.
Claim Objections
Claim 1 is objected to due to the recitation of “method of yielding”. The term should be amended to recite “method of producing”. Appropriate correction is required.
Claim 4 is objected to due to the recitation of “Mannich cyclase that purified from organisms”. It should be amended to recite “Mannich cyclase that is purified from organisms”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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 1-10 and 17 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.
Claims 1-6, 17 (claims 7-10 dependent thereon) is indefinite in the recitation of “Mannich cyclase” for the following reasons. The term is not a well-recognized term in the art such that one of skill in the art would know which cyclases are excluded or included by the term. While the term can be interpreted as a cyclase that is able to catalyze a Mannich cyclization, it is known in the art that there are enzymes having different enzymatic activities that can catalyze this reaction. Therefore, as written, it is unclear if the term refers to any enzyme that can catalyze this reaction. For examination purposes, it will be assumed that the term refers to a cyclase that can catalyze a Mannich cyclization reaction. Correction is required.
Claim 2 is indefinite in the recitation of “LolT” for the following reasons. The term is not well in the art and does not convey any particular structure for the cyclase. Therefore, in the absence of a sequence identifier recited, it is unclear as to what an LolT is. If a sequence identifier has been provided in the specification for this protein as originally filed, the claim could be amended to refer to that sequence identifier. Correction is required.
Claim 4 (claims 5-6 dependent thereon) is indefinite in the recitation of “organismal lysate” for the following reasons. It is unclear as to what the term “organismal” is. Correction is required.
Claim 4 (claims 5-6 dependent thereon) is indefinite in the recitation of “solution comprises enriched …cyclase” for the following reasons. While a solution can be enriched in a particular component, it is unclear as to what an enriched enzyme is. An enzyme by itself is a component, thus it is unclear as to what is an enzyme enriched in. Correction is required.
Claim 6 is indefinite in the recitation of “enriching the Mannich cyclase from the lysate” for the following reasons. While a solution can be enriched in a particular component, it is unclear as to how one could enrich an enzyme, which is by itself a component. If the intended limitation is purifying the cyclase obtained from the lysate, the claim can be amended accordingly. Correction is required.
Claim 8 (claims 9-10 dependent thereon) is indefinite in the recitation of “Substrate A” for the following reasons. The term “substrate A” does not convey any identity or structure for the substrate. Even if the argument is made that this term refers to what is shown in Figure 1, it is noted that as set forth in MPEP 2173.05(a), where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Claim 17 is indefinite in the recitation of “enriching a product generated from the substrate via…” for the following reasons. The product of the reaction catalyzed by cyclase is a single compound, and not a solution. While a solution can be enriched in a particular component, it is unclear as to how one could enrich a single product. If the intended limitation is purifying the product obtained from the reaction catalyzed by the cyclase, the claim can be amended accordingly. Correction is required.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-10 and 17 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow.
Claims 1-10 and 17 are directed in part to a method to produce a genus of azacyclic α-amino acids with a genus of cyclases having any structure, wherein said method requires contacting said genus of cyclases with a genus of substrates having any structure.
While the specification in the instant application discloses the azacyclic α-amino acids: pyrrolidine α-amino acid, piperidine α-amino acid, and loline, it provides no clue as to the structural elements required in any azacyclic α-amino acid that can be produced by the claimed method. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which azacyclic α-amino acids can be produced by the claimed method.
The claims encompass a large genus of azacyclic α-amino acids which are structurally unrelated. A sufficient written description of a genus of azacyclic α-amino acids may be achieved by a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no recited structural feature which is representative of all the members of the genus of azacyclic α-amino acids that can be produced by the recited claims, and there is no information as to which are the structural elements of the azacyclic α-amino acids that are essential for the recited method, or a correlation between structure and function which would provide those unknown structural features.
While the specification in the instant application discloses the cyclases: LolT (encoded by SEQ ID NO: 1) and LolD (encoded by SEQ ID NO: 2) it provides no clue as to the structural elements required in any cyclase that can produce any azacyclic α-amino acid. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which cyclases have the ability to produce any azacyclic α-amino acid.
A sufficient written description of a genus of cyclases may be achieved by a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no recited structural feature which is representative of all the members of the genus of cyclases that are essential for the recited method, or a correlation between structure and function which would provide those unknown structural features.
Furthermore, while the specification in the instant application discloses Substrate A, it provides no clue as to the structural elements required in any substrate that can produce any azacyclic α-amino acid after contacting cyclases. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which substrates can produce any azacyclic α-amino acid after contacting cyclases.
Therefore, one of ordinary skill in the art would not recognize from the disclosure that the Applicant was in possession of the claimed invention.
Claims 1-10 and 17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method producing a pyrrolidine α-amino acid, piperidine α-amino acid, or loline, comprising: providing the proteins encoded by SEQ ID NO: 1 and 2 in a solution; and contacting said proteins with Substrate A, does not reasonably provide enablement for a method to produce a genus of azacyclic alpha amino acids with a genus of cyclases having any structure, wherein said method requires contacting said genus of cyclases with a genus of substrates having any structure. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) the breadth of the claims. The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 1-10 and 17 broadly encompass (a) a method producing any azacyclic α-amino acid, comprising: providing any cyclase in a solution; and contacting the cyclase with any substrate. The enablement provided is not commensurate in scope with the claims due to the lack of knowledge regarding the structure/identity of any azacyclic α-amino acids that can be produced by any cyclase and any substrate with the recited method. In the instant case, the specification enables a method for producing a pyrrolidine α-amino acid, piperidine α-amino acid, and loline, comprising: providing proteins expressed by SEQ ID NO: 1 and 2 in a solution; and contacting said proteins with substrate A.
The amount of direction or guidance presented and the existence of working examples. The specification discloses a limited amount of azacyclic α-amino acids, cyclases and substrates. However, the specification fails to provide any clue as to the structural elements and features required to identify additional azacyclic α-amino acids, cyclases, and substrates that are encompassed by the claims.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The structural elements of an amino acid, enzyme, and substrate, determines its functional properties. While the art discloses a limited number of cyclases and substrates that produce azacyclic α-amino acids, neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can predict which cyclases and substrates would successfully perform the claimed method.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of determining enzymes’ ability to produce a specific product were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of cyclases and substrates to find a combination with the desired azacyclic α-amino acid product. In the absence of a rational and predictable scheme for selecting the combinations most likely to have the desired product, one of skill in the art would have to test an infinite number of said combinations.
Therefore, taking into consideration the extremely broad scope of the claims, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, the high degree of unpredictability, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Claim Rejections - 35 USC § 102 (AIA )
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-10 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gao et al. (Nature Catalysis , vol. 6, no. 6, June 2023; hereby “Gao”).
Claims 1-10 and 17 as interpreted are directed in part to a method for producing an azacyclic α-amino acid, comprising: providing a cyclase in a solution; and contacting the cyclase with a substrate, further comprising enriching a product generated from the substrate via the cyclase; wherein the cyclase is LolT; wherein the solution comprises a culture of live organisms heterologously expressing the cyclase; wherein the solution comprises enriched cyclase that purified from organisms that heterologously expressed the cyclase; or wherein the solution comprises an organismal lysate of organisms that heterologously expressed the cyclase comprising: expressing the cyclase in the organisms, wherein the expression of cyclase is heterologous; and lysing the organisms to generate a lysate, and enriching the cyclase from the lysate; wherein the substrate is selected from Substrate A ;wherein the substrate is Substrate A; wherein n is 1, 2, or 3; wherein m is 1, 2, or 3; wherein when n is 1, m is 1, 2 or 3, when n is 2 or 3, m is 1 or 2, when m is 1 or 2, n is 1, 2, or 3, and when m is 3, n is 1.
Gao teaches the synthesis of 1-azabyclic [Symbol font/0x61]-amino acids by LolT (Figure 3). Gao teaches the pathway for the pyrrolizidine formation of loline, wherein Substrate A contacts a cyclase (Figure 2). Gao teaches protein heterologous expression and purification wherein P. expansum LolT (XP_016595153.1) and E. uncinate LolD (Q5MNI5), E. coli BL21(DE3) strain (Novagen) were used for heterologous expression (Page 15 [3]). Gao teaches that after inducing protein expression the cells were harvested by centrifugation and resuspended in buffer and lysed on ice by sonication (Page 16 [1]). Gao teaches that enzymatic assays for LolT and LolD were performed in a reaction mixture that included an amino acid substrate in the assay buffer (50 mM K2HPO4, 50 µM PLP, pH 7.5) (Page 17 [3]).
Therefore, the teachings of Gao et al. anticipate the instant claims as written/interpreted.
Conclusion
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SYNPHANE SHELTON whose telephone number is (571)272-6318. The examiner can normally be reached 9:00am-7pm.
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, Robert Mondesi can be reached at (408) 918-7584. 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.
/S.L.S./Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
Prosecution Insights