DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1-20 are pending.
Priority
3. Acknowledgement is made of this continuation of U.S. Non-provisional Application No. 17/120646, filed on 12/14/2020, which is a divisional of U.S. Non-provisional Application No. 16/460147, filed on 07/02/2019, which claims domestic priority to U.S. Provisional Application Nos. 62/822301 and 62/695587, filed on 03/22/2019 and 07/09/2018, respectively.
Information Disclosure Statement
4. The IDSs filed on 09/03/2024 have been considered by the examiner and copies of the Form PTO/SB/08 are attached to the office action.
Claim Rejections - 35 USC § 112(a)
5. 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.
A. Written Description
6. Claims 1-20 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This new grounds of rejection is necessitated upon further consideration of the claims as a whole.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claims 1-18 are drawn to an engineered panthothenate kinase polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2, or a to a functional fragment thereof, wherein said polypeptide or fragment thereof comprises an amino acid substitution corresponding to amino acid positions 54, 157, 161, 261 and/or 308 in SEQ ID NO: 2, wherein said polypeptide has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate when compared the wild-type polypeptide having the amino acid sequence of SEQ ID NO: 2. The structure of the functional fragment thereof that results in a pantothenate kinase polypeptide having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate is unlimited.
Claims 19-20 are drawn to a polynucleotide sequence and a vector comprising the polynucleotide sequence encoding the engineered panthothenate kinase polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2, or a to a functional fragment thereof, wherein said polypeptide or fragment thereof comprises an amino acid substitution corresponding to amino acid positions 54, 157, 161, 261 and/or 308 in SEQ ID NO: 2, wherein said polypeptide has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate when compared the wild-type polypeptide having the amino acid sequence of SEQ ID NO: 2. The structure of the functional fragment thereof that results in a pantothenate kinase polypeptide having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate is unlimited.
In this case, the specification discloses the following representative species of engineered pantothenate kinase polypeptides having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate as encompassed the claims (i.e. pantothenate kinase comprising the amino acid sequence of SEQ ID NO: 2 with amino acid substitutions at positions corresponding to positions 54, 157, 161, 261 and/or 308 of SEQ ID NO: 2). There is no prior-art or disclosed teaching regarding which of the amino acids can vary from the representative species by either conservative or non-conservative substitutions and still result in a functional fragment that has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate and there is no disclosed or art-recognized correlation between and structure other than the disclosed sequences and mutations to have increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate activity. The reference of Singh et al. (Current Protein and Peptide Science, 2017; cited on IDS filed on 09/03/2024) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top]. The reference of Zhang et al. (Structure, 2018; cited on IDS filed on 09/03/2024) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
Given what is known in the art about the likely outcome of substitutions on structure, conservation of structure is not necessarily a surrogate for conservation of function. In this case, there is no disclosed correlation between structure and function. While general knowledge in the art may have allowed one of skill in the art to identify other proteins expected to have the same or similar tertiary structure of a polypeptide that can have increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate activity, there is no general knowledge in the art about ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate activity that general similarity of structure confers the activity. Accordingly, one of skill in the art would not accept the disclosure of pantothenate kinase comprising the amino acid sequence of SEQ ID NO: 2 with amino acid substitutions at positions corresponding to positions 54, 157, 161, 261 and/or 308 of SEQ ID NO: 2 as being representative of all functional fragments having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate activity as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of amino acid substitution, fails to satisfy the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph.
B. Scope of Enablement
7. Claims 1-20 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 pantothenate kinase comprising the amino acid sequence of SEQ ID NO: 2 with amino acid substitutions at positions corresponding to positions 54, 157, 161, 261 and/or 308 of SEQ ID NO: 2 and having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate activity, does not reasonably provide enablement for all functional fragments having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is mostly nearly connected, to make and/or use the invention commensurate in scope with these claims. This new grounds of rejection is necessitated upon further consideration of the claims as a whole.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
(A) The breadth of the claims: Claims 1-18 are drawn to an engineered panthothenate kinase polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2, or a to a functional fragment thereof, wherein said polypeptide or fragment thereof comprises an amino acid substitution corresponding to amino acid positions 54, 157, 161, 261 and/or 308 in SEQ ID NO: 2, wherein said polypeptide has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate when compared the wild-type polypeptide having the amino acid sequence of SEQ ID NO: 2. The structure of the functional fragment thereof that results in a pantothenate kinase polypeptide having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate is unlimited.
Claims 19-20 are drawn to a polynucleotide sequence and a vector comprising the polynucleotide sequence encoding the engineered panthothenate kinase polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2, or a to a functional fragment thereof, wherein said polypeptide or fragment thereof comprises an amino acid substitution corresponding to amino acid positions 54, 157, 161, 261 and/or 308 in SEQ ID NO: 2, wherein said polypeptide has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate when compared the wild-type polypeptide having the amino acid sequence of SEQ ID NO: 2. The structure of the functional fragment thereof that results in a pantothenate kinase polypeptide having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate is unlimited.
(C) The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the recited functional fragments having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate are structurally unlimited.
It is well-known in the prior art that the amino acid sequence of a polypeptide determines the polypeptide’s functional properties. The positions within a protein's sequence where modifications can be made with a reasonable expectation of success in obtaining a polypeptide having the desired activity/utility are limited in any protein and the result of such modifications is highly unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g., multiple substitutions. The reference of Singh et al. (Current Protein and Peptide Science, 2017; cited on IDS filed on 09/03/2024) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top]. The reference of Zhang et al. (Structure, 2018; cited on IDS filed on 09/03/2024) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
It is well-known in the art that even a single amino acid alteration can alter the folding of a polypeptide. See, e.g., MPEP 2144.08.II.A.4.(c), which states, “[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution (“the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein.” Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990).”
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following examples of engineered pantothenate kinase polypeptides having increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate, i.e. pantothenate kinase comprising the amino acid sequence of SEQ ID NO: 2 with amino acid substitutions at positions corresponding to positions 54, 157, 161, 261 and/or 308 of SEQ ID NO: 2. Other than these working examples, the specification fails to disclose any other working examples of functional fragments having the desired activity of increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate as encompassed by the claims.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Double Patenting
8. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,110,513. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-17 of the ‘513 patent recite an engineered pantothenate kinase polypeptide comprising an amino acid sequence having at least 85% sequence to SEQ ID NO: 2, wherein said engineered pantothenate kinase comprises an amino acid substitution set corresponding to F15L, V27N, and W283H/L in SEQ ID NO: 2, wherein said engineered pantothenate kinase has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate when compared the wild-type polypeptide having the amino acid sequence of SEQ ID NO: 2. The dependent claims are further limited to mutations in positions that are encompassed by the claims and polynucleotides and vectors encoding the pantothenate kinase.
10. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 10,889,806. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-26 of the ‘806 patent are recite an engineered pantothenate kinase polypeptide comprising an amino acid sequence having at least 85% sequence to SEQ ID NO: 2, wherein said engineered pantothenate kinase comprises an amino acid substitution set corresponding to amino acid position 277 and/or 281 in SEQ ID NO: 2, wherein said engineered pantothenate kinase has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate when compared the wild-type polypeptide having the amino acid sequence of SEQ ID NO: 2. The dependent claims are further limited to mutations in positions that are encompassed by the claims and polynucleotides and vectors encoding the pantothenate kinase.
Conclusion
11. Status of the claims:
Claims 1-20 are pending.
Claims 1-20 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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