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
Claims 1-20, and 24-32 are pending. Claims 1-20 are withdrawn. Claims 24-32 are pending and under examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/14/2025 has been entered.
Response to Arguments
With respect to the rejection of claims 24-32 under 35 USC 112(a), Applicant's arguments filed 10/15/2025 have been fully considered but they are not persuasive. Applicant argues that the one of skill would conclude that Applicant was in possession of the subject matter of the present claims because the complete structures of the proteins are provided and are identified by their associated functions. However, said function was identified using a proprietary endolysin discovery software (Example 1), but nowhere in the prior art or in the instant specification is said function demonstrated.
As discussed in the rejection below, MPEP 2163.05 II states “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us].’”
The polypeptides disclosed in Figure 6, are polypeptides that are not claimed, exhibit different levels of Gardnerella killing activity, indicating that there is functional variation within the genus. Therefore, the disclosed species are not representative of the entire genus of claimed polypeptides that are capable of killing Gardnerella spp.
Claim Objections
Claims 25, 26, and 28 are objected to because of the following informalities:
In claim 25, the word “a” in front of “bacteria” in line 3 should be removed.
Claim 26 contains an extra period at the end of the sentence.
In claim 28, the word “and” before G. swidsinskii should be removed.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 24-32 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 of killing Gardnerella vaginalis comprising contacting Gardnerella vaginalis with a polypeptide comprising the amino acid sequence selected from SEQ ID NOs: 21, 73, 74, or 75, does not reasonably provide enablement for treating all bacterial infections comprising administering to a subject a polypeptide of the instant invention. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Per MPEP 2164.01(a), the following eight factors should be considered when determining whether the person of ordinary skill in the art would face undue experimentation to make and/or use the invention: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered.
Nature of the Invention: Claim 24 is drawn to a method of treating a bacterial infection comprising administering a therapeutically effective amount of a composition selected from 1) a polypeptide comprising a hydrolase domain comprising SEQ ID NO:2-6, or an amino acid sequence having at least 95% sequence identity to SEQ ID NO:2-6, 2) an isolated nucleotide encoding the polypeptide, and 3) a vector comprising the isolated nucleotide. Claim 25 recites that the method disperses, treats, and/or decolonizes a bacteria biofilm, and/or kills, or inhibits growth of, bacteria. Claim 26 limits the bacteria to Gardnerella spp. Claim 27 limits the bacterial infection to bacterial vaginosis. Claim 28 limits the bacterial to G. leopoldii, G. piotii, G. swidsinksii, and G. vaginalis. Claim 29 recites that the polypeptide further comprises a cell wall binding domain. Claim 30 recites that the cell wall binding domain binds to Gardnerella spp. Claim 31 limits the cell wall binding domain to SEQ ID NO:9-13 or an amino acid sequence with at least 95% identity to SEQ ID NO:9-13. Claim 32 recites that the polypeptide comprises any one of SEQ ID NO:22-26, 51-61, 76, or 77, or an amino acid sequence with at least 95% sequence identity to SEQ ID NO:22-26, 51-61, 76, or 77.
Breadth of the Claims: Independent claim 24 is not specific to a particular bacterial infection. Dependent claim 27 limits the infection to bacterial vaginosis.
State of the Prior Art and Unpredictability:
Corsini et al., (WO2020/225335A1, IDS) teaches phage endolysins comprising an N-terminal catalytic domain, a C-terminal cell-wall binding region, and a linker region (para. [0009]) that exhibit killing activity against 4 Gardnerella strains in vitro (para. [0025]). Corsini does not demonstrate that the endolysins can treat bacterial vaginosis in vivo. Corsini does not teach that the endolysins may be used to treat any bacterial infection, and does not teach the sequences of the instant claims. There are no prior art references that teach sequences with 95-100% sequence identity to those of the instant claims.
Guidance in the Specification and Working Examples: The specification discloses that the polypeptides of the instant invention comprise endolysins with anti-bacterial activity against Gardnerella spp. (p. 6, line 25). The specification only discloses in vitro experiments in which endolysins comprising SEQ ID NOs: 21, 73, 74, and 75, and SEQ ID NOs: 21, 73, and 74 with 6XHis tags, were incubated on agar plates with a dried suspension of G. vaginalis (Example 4; Figure 6). The specification also discloses an in vitro experiment demonstrating that the two endolysin polypeptides do not have activity against other bacteria isolated from the vaginal flora (Figure 8). However, the specification does not disclose any experiments demonstrating the activity of the endolysin polypeptides against Gardnerella spp. other than G. vaginalis, and does not disclose any in vivo experiments in which a bacterial infection was successfully treated with the polypeptides of the instant invention.
Amount of Experimentation Necessary: Based on Applicant’s disclosure and the lack of predictability in the state of the art prior to the effective filing date of the claimed invention, the person of ordinary skill would have faced undue experimentation. The person of ordinary skill would have had to determine the effective amount of the claimed polypeptides to be administered to a subject with a bacterial infection, and would have had to determine the most effective mode of administration.
Therefore, based on the above analysis, undue experimentation would be required by the artisan of ordinary skill to practice the claimed invention. Thus, the claims are not fully enabled by the disclosure.
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 24-32 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claim 24 is drawn to a method of treating a bacterial infection comprising administering a therapeutically effective amount of a composition selected from 1) a polypeptide comprising a hydrolase domain comprising SEQ ID NO:2-6, or an amino acid sequence having at least 95% sequence identity to SEQ ID NO:2-6, 2) an isolated nucleotide encoding the polypeptide, and 3) a vector comprising the isolated nucleotide. Claim 29 recites that the polypeptide further comprises a cell wall binding domain and claim 31 recites that the cell wall binding domain comprises SEQ ID NO:9-13 or an amino acid sequence with at least 95% identity to SEQ ID NO:9-13. Claim 32 recites that the polypeptide comprises any one of SEQ ID NO:22-26, 51-61, 76, or 77, or an amino acid sequence with at least 95% sequence identity to SEQ ID NO:22-26, 51-61, 76, or 77.
MPEP 2163.05 II states “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us].’”
The instant specification reduces to practice CCB2.1 (SEQ ID NO:21), CCB2.2 (SEQ ID NO:73), CCB2.3 (SEQ ID NO:74), and CCB2.4 (SEQ ID NO:75), which comprise hydrolase and cell wall binding domains (Figure 6). However, none of SEQ ID NO:21, 73, 74, and 75 are claimed. Therefore, Applicant has not reduced to practice any of the claimed polypeptides. The specification does not disclose the claimed polypeptides, or polypeptides with up to 5% sequence divergence from said polypeptides, that are capable of treating a bacterial infection. The instant specification does not disclose what structural properties are required for the endolysin polypeptides to maintain killing activity against Gardnerella spp. Therefore, the disclosed species are not representative of the entire genus of claimed polypeptide variants.
Corsini et al., (WO2020/225335A1, IDS) teaches phage endolysins comprising an N-terminal catalytic domain, a C-terminal cell-wall binding region, and a linker region (para. [0009]) that exhibit killing activity against 4 Gardnerella strains in vitro (para. [0025]). Corsini does not demonstrate that the endolysins can treat bacterial vaginosis in vivo, and does not teach the sequences of the instant claims. Corsini does not disclose the hydrolase domain residues that are responsible for killing activity against Gardnerella spp, and does not disclose which cell wall binding domain residues are responsible for binding to the cell wall of Gardnerella spp.
In summary, neither the instant specification, nor the prior art, discloses a structure-function relationship between conserved amino acid residues in the hydrolase enzyme structure and the claimed Gardnerella spp. killing activity. One of ordinary skill in the art cannot reasonably predict which residues of the claimed sequences may be modified to generate a functional endolysin with activity against Gardnerella spp. Based on the instant disclosure, those skilled in the art would not conclude that the applicant was in possession of all claimed variants.
Double Patenting
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.
Claims 24-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 48-50 of copending Application No. 18/037,632 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the conflicting claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 48 of ‘632 recites a method of treating or preventing a bacterial infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition of claim 45. Claim 45 of ‘632 recites a composition comprising the polypeptide of claim 30. Claim 30 recites a polypeptide having anti-Gardnerella spp. activity comprising a hydrolase domain wherein the hydrolase domain comprises an amino acid sequence selected from any one of SEQ ID NOs: 5, 3, 6, 2, 4, or 1.
Claim 49 of ‘632 recites the method according to claim 48 wherein the polypeptide or composition prevents, disperses, treats and/or decolonizes a bacterial biofilm and/or kills or prevents growth of a bacterial wherein the bacteria include Gardernella spp.
Claim 50 of ‘632 recites a method according to claim 48 wherein the bacterial infection is bacterial vaginosis.
Instant claim 24 is unpatentable over claim 30, 45, and 48 of ‘632 because all claims require a method of treating a bacterial infection in a subject, the method comprising administering a composition to a subject wherein the composition comprises a polypeptide with a hydrolase domain, the hydrolase domain comprising at least one of SEQ ID NO:2-6.
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278
596
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SEQ ID NO:2 of ‘632 is 100% identical to instant SEQ ID NO:2 (see alignment below).
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344
589
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SEQ ID NO:3 of ‘632 is 100% identical to instant SEQ ID NO:3 (see alignment below).
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340
594
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SEQ ID NO:4 of ‘632 is 100% identical to instant SEQ ID NO:4 (see alignment below)
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339
592
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SEQ ID NO:5 of ‘632 is 100% identical to instant SEQ ID NO:5 (see alignment below).
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340
601
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SEQ ID NO:6 of ‘632 is 100% identical to instant SEQ ID NO:6 (see alignment below)
Instant claims 25, 26, and 28 are unpatentable over claim 49 of ‘632 because all claims require a method in which the composition comprising a polypeptide with a hydrolase domain comprising the amino acid sequences recited above prevents, disperses, treats and/or decolonizes a bacterial biofilm and/or kills growth of bacteria, wherein the bacterial include Gardnerella spp., including G. leopoldii, G. piotti, G. swidsinskii and G. vaginalis.
Instant claim 27 is unpatentable over claim 50 of ‘632 because both claims require a method of treating a bacterial infection wherein the infection is bacterial vaginosis.
The claims at issue are broader in scope and are therefore anticipated by claims 30, 45, and 48-50 of ‘632.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657
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