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
1. Original claims 1-5 filed on 2/27/23 are under consideration in this Office Action.
2. IDS filed 10/18/24 is acknowledged. A signed copy of the IDS is provided with this Office Action.
3. Priority
Applicant’s claim for domestic priority under 35 U.S.C. 119(e), filed 3/26/15 & 9/24/15, is acknowledged.
4. Drawings
The drawings filed on 2/27/23 are acknowledged.
5. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
6. 35 U.S.C. § 112, first paragraph (Written Description)
Claims 1-2 & 4-5 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.
The claimed invention is directed to the following genus claims.
1. A method of identifying a fungicidal Paenibacillus sp. strain with broad spectrum antifungal activity, the method comprising: a) sequencing FusA-A3 in the Paenibacillus sp. strain to characterize a variant fusaricidin synthetase; b) assaying the fungicidal activity of the Paenibacillus sp. strain with the variant fusaricidin synthetase; c) selecting the fungicidal Paenibacillus sp. strain as having broad spectrum antifungal activity if the Paenibacillus sp. strain comprises the variant fusaricidin synthetase and demonstrates increased fungicidal activity compared to a reference Paenibacillus sp. strain comprising a wild-type fusaricidin synthetase, and d) culturing the fungicidal Paenibacillus sp. strain to produce a fungicidal fermentation product.
2. The method of claim 1, wherein the variant fusaricidin synthetase comprises a deletion in FusA-A3 of at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or ten amino acid residues that determine substrate specificity.
3. The method of claim 2, wherein the deletion comprises one or more amino acid residues that correspond to positions Asp254, Ala255, Ser258, Thr297, Leu318, Ala320, Gly341, le349 and Cys350 of SEQ ID NO: 11 or Asp254, Ala255, Ser258, Thr297, Leu318, Ala320,Ala341, Val349, and Cys350 of SEQ ID NO: 9 or Asp254, Ala255, Ser258, Thr297, Leu318, Ala320, Gly341, Val349 and Cys350 of SEQ ID NO: 1.
4. The method of claim 2, further comprising quantifying a Paeniserine and/or Paeniprolixin produced by the Paenibacillus sp. strain and selecting the Paenibacillus sp. strain as having broad spectrum antifungal activity if the Paenibacillus sp. strain produces increased levels of the Paeniserine and/or Paeniprolixin compared to the reference Paenibacillus sp. strain comprising a wild-type fusaricidin synthetase.
5. The method of claim 2 further comprising quantifying the levels of fusaricidins with a tyrosine or a phenylalanine at amino acid residue (3) (e.g., LiF03a, LiF03b, LiF03c, LiF03d, LiF07a, LiF07b, LiF07c, and/or LiF07d) and selecting the Puenibacillus sp. strain having decreased or undetectable levels of fusaricidins with a tyrosine or a phenylalanine at amino acid residue (3) compared to fusaricidins with a tyrosine or a phenylalanine at amino acid residue (3) quantified in a reference Paenibacillus sp. strain comprising a wild-type fusaricidin synthetase.
The claims are described by functional limitations only (see for example claim1-2 & 4-5) and are devoid of a reference structure to the method using the claimed variant fusaricidin synthetase. The claimed invention encompasses a genus of variant fusaricidin synthetase not adequately described.
The instant specification describes - A method of identifying a fungicidal Paenibacillus sp. strain with broad spectrum antifungal activity, the method comprising: a) sequencing FusA-A3 in the Paenibacillus sp. strain to characterize a variant fusaricidin synthetase; b) assaying the fungicidal activity of the Paenibacillus sp. strain with the variant fusaricidin synthetase; c) selecting the fungicidal Paenibacillus sp. strain as having broad spectrum antifungal activity if the Paenibacillus sp. strain comprises the variant fusaricidin synthetase and demonstrates increased fungicidal activity compared to a reference Paenibacillus sp. strain comprising a wild-type fusaricidin synthetase, and d) culturing the fungicidal Paenibacillus sp. strain to produce a fungicidal fermentation product, wherein the product is Paeniserine and/or Paeniprolixin; wherein the variant fusaricidin synthetase comprises a deletion in FusA-A3 of at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what isclaimed."). Thus, an applicant complies with the written description requirement "bydescribing the invention, with all its claimed limitations, not that which makes it obvious,"and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966."Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents" of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents" of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include "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. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case is discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
Moreover, Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir.1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
7. Claim Rejections - 35 USC § 112 (second paragraph)
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 2-5 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 pre-AIA the applicant regards as the invention.
Claim 2 recite - The method of claim 1, wherein the variant fusaricidin synthetase comprises a deletion in FusA-A3 of at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or ten amino acid residues that determine substrate specificity.
While only 9 deletion in each set corresponding to SEQ ID Nos. 1, 9 & 11 are disclosed, as is evident from claim 3, the inclusion of or ‘ten amino acid residue in claim 2 is indefinite.
Claims 3-5 are included in the rejection for failing to correct the defect present in the base claim(s).
Claim 5 recites “further comprising quantifying the levels of fusaricidins with a tyrosine or a phenylalanine at amino acid residue (3) (e.g., LiF03a, LiF03b, LiF03c, LiF03d, LiF07a, LiF07b, LiF07c, and/or LiF07d)”.
First the use of expression ‘e.g’ attempts to give both broad and narrow meaning to the scope of the above claims. The claim is unclear.
Second – the expression “tyrosine or a phenylalanine at amino acid residue (3) (e.g., LiF03a, LiF03b, LiF03c, LiF03d, LiF07a, LiF07b, LiF07c, and/or LiF07d)”, is unclear regarding the number (3); as well as the abbreviations/residues “LiF03a, LiF03b, LiF03c, LiF03d, LiF07a, LiF07b, LiF07c, and/or LiF07d)”; and further clarity is lacking as no reference sequence is assigned to correspond to the residues.
Amendment and clarification is required.
8. 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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by WO 2007086645 A1.
WO 2007086645 A1 teaches isolation of fusaricidin synthetase from Gram-positive Paenibacillus sp. and a gene encoding the same, more precisely a fusaricidin synthetase isolated from Paenibacillus polymyxa E681, a gene encoding thereof and a preparation method of fusaricidin or its derivatives using the gene cluster. The fusaricidin synthetase of the present invention can be effectively used for the increase of productivity of fusaricidin and the development of a novel antibiotic. See abstract.
Claims 1-9 & 17 in the WO 2007086645 A1 are as follows.
[Claim 1] A polypeptide involved in fusaricidin synthesis or a variant thereof.
[Claim 2] The polypeptide according to claim 1, which is represented by SEQ. ID. NO: 2.
[Claim 3] The polypeptide according to claim 1, wherein the fusaricidin is selected from a group consisting of fusaricidin A, fusaricidin B, fusaricidin C, fusaricidin D, LI-F03, LI-F04, LI-F05, LI-F07 and LI-F08.
[Claim 4] The polypeptide according to claim 1, wherein the polypeptide contains one or more modules and each module contains at least two domains selected from a group consisting of A, C, T, E and TE domains.
[Claim 5] The polypeptide according to claim 4, wherein the structure has been modified by the addition, deletion or substitution of one or more modules, domains or amino acids, or the linkage between hydroxyl acid and D- and L-amino acid, mutation and oxidation of peptide chain, acylation, glycosylation, N-methylation and heterocyclic ring formation.
[Claim 6] A gene encoding the polypeptide of claim 1 or claim 5.
[Claim 7] The gene according to claim 6, which is represented by SEQ. ID. NO: 1.
[Claim 8] A recombinant vector containing the gene of claim 6.
[Claim 9] A host cell transformed with the vector of claim 8.
[Claim 17] A preparation method of fusaricidin or its derivatives comprising the following steps: 1) Constructing a recombinant expression vector by inserting a gene encoding the fusaricidin synthetases of claim 6 into an expression vector; 2) Transforming a host cell with the expression vector containing the gene of step 1);3) Culturing the transformant of step 2); and4) Isolating and purifying fusaricidin or its derivatives from the culture product of step 3) .
The reference provides a polypeptide involved in fusaricidin synthesis and a gene encoding the same. The polypeptide involved in fusaricidin synthesis of the invention is represented by SEQ. ID. NO: 2 and its variants, that is, other polypeptides which are equally functioning but modified by addition, deletion and substitution of one or more modules, domains and/or amino acids are also included in the criteria of the invention.
The reference further teaches in reports embedded therein on the excellent germicidal activity of fusaricidin against pathogenic Gram-positive bacteria and plant pathogenic fungi (page 5, lines 1-5). Thus accounting for the broad spectrum antifungal activity if the Paenibacillus sp. strain comprises the variant fusaricidin synthetase and demonstrates increased fungicidal activity. This is also supported by the works of others as follows.
A brief background is on page 4 and is reproduced here for understanding the reasons for the rejection. “Fusaricidin has excellent germicidal activity to plant pathogenic fungi such as Fusarium oxysporum, Aspergillus niger, Aspergillus oryzae and Penicillum thomii, and particularly fusaricidin B has germicidal activity to Candida albicans and Saccharomyces cerevisiae. Fusaricidin also has excellent germicidal activity to Gram-positive bacteria including Staphylococcus aureus (Kajimura Y and Kaneda M. J. Antibiotics 49:129-135, 1996; Kajimura Y and Kaneda M. J". Antibiotics 50:220-228, 1997). In addition, fusaricidin has antifungal activity against Leptosphaeria maculans which causes black root rot of canola (Beatty PH and Jensen SE. Can. J. Microbiol. '48: 159-169, 2002)”.
The reference anticipates claim 1.
9. No claim is allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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 B Mondesi can be reached on 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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940