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 .
Claim Status
Claims 30-50 are pending in the application following the Reply filed 06/15/2026. Claims 30-47 are withdrawn. Claims 48-50 are presently considered.
Withdrawn
The objections to claims 48-50 are withdrawn in light of the amendments.
The rejection of claim 49 under 35 U.S.C. 112(b) is withdrawn in light of the amendments.
The written description rejection of claims 49-50 under 35 U.S.C. 112(a) is withdrawn in light of the amendments. In particular, the claims are no longer drawn to polypeptide fragments or sequences having as little as 80% sequence identity to the claimed SEQ ID NOs. However, the rejection of claim 48 is maintained for the reasons cited in the present rejection. See also Response to Arguments.
The scope of enablement rejection of claims 48-50 under 35 U.S.C. 112(a) is withdrawn in light of the amendments. In particular, the claims are no longer drawn to a method of “preventing” a bacterial infection. See Response to Arguments for further discussion.
The rejection of claims 48-50 under 35 U.S.C. 102 is withdrawn in light of the amendments. See Response to Arguments for further discussion.
Claim Interpretation
Claim 48 recites “A method of treating a bacterial infection in a subject”, wherein the term, “subject”, is not defined by the specification. The broadest reasonable interpretation of the claim is that the “subject” can be any subject, because the limitation of “preventing” does not require the subject to have a bacterial infection. As dependent claim 49 recites the bacteria to “optionally” include Gardnerella spp. as a further limitation, it is broadly interpreted that the limitation of “a bacterial infection” in claim 48 is directed to any infection caused by any bacteria. As any subject would be susceptible to a bacterial infection, the BRI of the claim is a method to treat any bacterial infection in any subject.
Claim Rejections - 35 USC § 112(a) – Written Description
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.
Claim 48 is 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.
Brief Statement of the Issue(s)
The claim recites a method comprising the administering of polypeptides (i.e., endolysins) comprising hydrolases, wherein the polypeptides comprise a vast and varied genus of undisclosed structures capable of treating any bacterial infection. While the claimed hydrolase domains are disclosed to have specific activity against Gardnerella, it is apparent in view of the instant specification, as well as the prior art, that the activity of the polypeptides (i.e., endolysins) which comprise these domains require further structure (i.e., cell wall binding domains) in order to have this activity against other bacteria. The written description in the specification is insufficient for one to envisage the full breadth of the claimed genus of enzymes having this activity for the reasons set forth in the following analysis.
Claim Scope
Claim 48 is drawn to a method of treating a bacterial infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition, wherein the composition comprises a polypeptide, an isolated nucleic acid encoding the polypeptide, a vector comprising the nucleic acid, or a cell comprising the isolated nucleic acid (claim 45), wherein the polypeptide has anti-Gardnerella spp. activity and comprises a hydrolase domain, wherein the hydrolase domain comprises or consists of an amino acid sequence selected from any one of SEQ ID NOs 2-6, or a sequence having at least 95% identity thereto (claim 30). As discussed under Claim Interpretation, the method is directed to treating any bacterial infection in any subject. Therefore, the claimed genus necessarily includes species of the claimed polypeptides having activity against each and every bacteria that is within this scope, as discussed further below.
The specification states that endolysins are polypeptides produced by bacteriophages, which normally comprise two domains, a catalytic or hydrolase domain, and a cell wall binding domain (CBD), and that the specificity of an endolysin is often attributed to the cell wall binding domain, which recognizes a cell wall feature specific to the bacteria that it targets (see pg. 2, lines 9-10, 16-19 and 23-24). In view of the prior art of Fernández-Ruiz, et al. (Thousands of Novel Endolysins Discovered in Uncultured Phage Genomes. Front Microbiol. 2018 May 18;9:1033; cited on Form 892), bacteriophage endolysins are a diverse class of enzymes, thousands of which have been discovered, and the bacteriophages that produce them are the most diverse biological entities on earth (see Abstract; pg. 1, para. 1).
Thus, it is unclear whether the claim scope encompasses trillions of species (i.e., potential hydrolase/CBD combinations) or perhaps only a few in view of the functional requirements (i.e., anti-bacterial activity against some unknown range of bacteria) set forth in the claim(s). Accordingly, the claim scope reasonably appears to be vast and highly varied.
Actual Reduction to Practice
The specification discloses that the invention relates to the treatment of bacterial infections, in particular bacterial vaginosis, using novel polypeptides (see pg. 1, lines 1-5). However, the specification has only reduced to practice the bacteriolytic activity of polypeptides CCB2.1 (SEQ ID NO: 21), CCB2.2 (SEQ ID NO: 73), CCB2.3 (SEQ ID NO: 74), CCB2.4 (SEQ ID NO: 75), CCB3.2 (SEQ ID NO: 76), CCB4.1 (SEQ ID NO: 23), CCB4.2 (SEQ ID NO: 77), CCB7.1 (SEQ ID NO: 25), and CCB8.1 (SEQ ID NO: 26) (see FIG. 6; Table 4 on pgs. 15-22), all of which have different levels of activity. Moreover, the SEQ ID NOs representing these polypeptides are not recited by the claims at issue.
Examiner notes that the polypeptides of Applicant’s Examples are longer sequences comprising SEQ ID NOs 1-6. For example, CCB3.1 (SEQ ID NO: 22) is 298 residues in length and comprises the hydrolase domain of SEQ ID NO: 2, which is 122 residues in length. Hence, the polypeptides reduced to practice required additional structure compared to those recited in the claims. Moreover, Applicant’s examples only demonstrate the activity of the endolysins against strains of Gardnerella vaginalis (see, e.g., pg. 37, lines 16-21; pg. 40, lines 29-34), and the inventors further demonstrate their selectivity towards Gardnerella spp. by experiments showing that the endolysins did not have any antimicrobial activity against other organisms found within the vaginal microbiome (see pg. 42, lines 15-17).
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within 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]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.") (Emphasis added).
Finally, satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
In the instant case, a reduction to practice demonstrating the use of the claimed hydrolases against only one species of bacteria, disclosed as having specificity to only said one species of bacteria, is reasonably not sufficient to show possession for a method that encompasses treating any bacterial infection, or to a genus of endolysins that can be engineered to have activity against any bacteria.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
The specification teaches that endolysins normally consist of two domains: a catalytic domain, such as a hydrolase domain (typically located at the N-terminal of the polypeptide), which cleaves specific motifs in the peptidoglycan layer, and a cell wall binding domain (classically located at the C-terminal of the polypeptide), which is involved in specific binding and processing of the bacterial peptidoglycan. However, the specification teaches this typical architecture is not a defined characteristic of all endolysins. The specification teaches that some endolysins can comprise catalytic domains and cell wall binding domains in different orientations, and endolysins that target “certain gram negative bacteria” may not comprise a dedicated cell wall binding domain. The specification also teaches that specificity of an endolysin is often attributed to the cell wall binding domain, which recognizes a cell wall feature specific to the bacteria that it targets. See specification at pg. 2, lines 16-24. The specification also teaches that the cell wall binding domain may comprise or consist of one of SEQ ID NOs 7-13, or a sequence having at least 80% identity thereto, or a fragment thereof (see pg. 10 lines 24-30; Table 2).
However, there is zero disclosure of any structure-function relationship between the amino acid sequences of these cell wall binding domains, their fragments, or their corresponding functions, that appears to relate to their antimicrobial specificity or function. While it may be appreciated that endolysins have a modular structure, allowing for unknown number of possible hydrolase/CBD combinations, the specification does not, for example, disclose any combination(s) that would be expected to confer activity against any bacteria, other than Gardnerella. Therefore, the disclosure does not meaningfully disclose an unambiguous structure/ function relationship permitting an artisan to identify, a priori, which exact structures do or do not satisfy the claimed genus.
Predictability in the Art
Broendum et al. (previously cited; hereafter, “Broendum”) teach that bacteriophage-encoded endolysins can recognize and bind specific bacteria (see Abstract), but the current understanding of how the structure of endolysins facilitate their function is still modest (see pg. 892, col. 1, para. 2). Broendum teaches that the specificity of endolysins for their bacterial host can vary from an entire bacterial genus down to the strain level (see pg. 879, col. 2, para. 1). Broendum teaches that the cell-wall binding domain (CBD) confers specificity to endolysins by recognizing and binding to ligand molecules, and such specificity can be broad, encompassing an entire bacterial genus or even multiple genera, or narrow, restricted down to the serovar or even strain level (see pg. 886, col. 2, para. 2). However, Broendum teaches that not all endolysins require a CBD for lytic activity (see pg. 890, col. 1, para. 2). Broendum teaches that modular design can facilitate simple domain swapping experiments to alter endolysin specificity and improve their activity; however, whether the effects are additive, synergistic or detrimental cannot yet be predicted (see pg. 890, col. 2, para. 2).
Hence, while the prior art indicates that fusing different CBD domains to different hydrolase domains can result in a functioning endolysin, possibly conferring new specificity or enhanced effects, there was only a modest understanding at the time of filing of how the structure of an endolysin relates to its function, and it was not predictable which combinations would achieve which effects.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
The Federal Circuit has explained that a specification cannot always support expansive
claim language and satisfy the requirements of 35 U.S.C. 112 "merely by clearly describing one
embodiment of the thing claimed." LizardTech v. Earth Resource Mapping, Inc., 424 F.3d 1336,
1346, 76 USPQ2d 1731, 1733 (Fed. Cir. 2005). See also Tronzo v. Biomet, 156 F.3d at 1159, 47
USPQ2d at 1833 (Fed. Cir. 1998)(holding that the disclosure of a species in a parent application
did not provide adequate written description support for claims to a genus in a child application
where the specification taught against other species).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional requirements and some minimal consensus structure; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that the skilled artisan cannot envisage what structures infringe or do not infringe upon the pending claim scope.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 48-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Corsini (US 20220315908 A1; effectively filed 05/08/2019; previously cited), in further view of Landlinger, et al. (Engineered phage endolysin eliminates Gardnerella in bacterial vaginosis without damaging the healthy vaginal microbiome. medRxiv 2020.10.21.20216853. Posted October 27, 2020; cited on Form 892), hereafter, “Landlinger”, and GenBank WP 075038579.1.
Regarding claim 48, Corsini teaches a method of treating a bacterial infection, comprising administering to a subject in need thereof a recombinant endolysin (see claim 12), wherein said bacterial infection is bacterial vaginosis (see claim 14). Corsini teaches the method for treating bacterial infections and disorders, such as bacterial vaginosis (BV), comprising administering to the subject in need a therapeutically effective amount of the endolysin (see pg. 6, para. [0075]). Corsini teaches that the distinct gene expression pattern of G. vaginalis, as well as the physical structure of its biofilms, increases bacterial resistance to many negative stimuli including pH extremes, host immune defenses and antibiotics (see pg. 1, para. [0008]). Therefore, there is a great need for new methods and compositions to treat G. vaginalis infections and particularly BV, e.g. by selectively killing bacterial cells of the genus Gardnerella, preferably without harming the beneficial Lactobacilli while they re-populate the vagina (see pg. 1, para. [0009]).
Landlinger teaches that bacterial vaginosis (BV) is characterized by an imbalance of the vaginal microbiome in which the normally predominant lactobacilli are replaced by other bacterial species, characterized by the formation of biofilm on the vaginal epithelium, which is initiated by strains of the bacterium Gardnerella (see pg. 4, “Background”). In Landlinger’s study, it was investigated whether a therapy based on bacteriophage endolysins which specifically lyse Gardnerella would be a promising alternative to broad-spectrum antibiotics and antiseptics (see pg. 4, “Objective”). Landlinger teaches that BV is a very common disorder in women of reproductive age, is associated with an increased risk of preterm delivery, low birthweight, infertility, and early spontaneous abortion, and is a high-risk factor for sexually transmitted diseases, including HIV (see pg. 6, lines 73-78).
Landlinger teaches that bacteriophage-encoded peptidoglycan hydrolases, also called endolysins, are a promising alternative to antibiotics, and have been shown to be particularly effective against Gram-positive bacteria (see pgs. 7-8, lines 121-126). Landlinger teaches that bacteriophage endolysins generally have a modular structure consisting of one or more enzymatically active domain (EAD)s connected to at least one cell wall-binding domain (CBD) which can both contribute to the specificity for a given genus or species of bacteria (see pg. 8, lines 130-133).
Landlinger teaches that no bacteriophages that infect Gardnerella have yet been isolated; however, prophages encoding for endolysins are present in the Gardnerella genomes, which can be identified using an in silico approach (see pg. 8, lines 134-139). Landlinger teaches that multiple Gardnerella genomes have been sequenced that contain DNA regions that are predicted to be of prophage origin, which can be identified using Basic Local Alignment Search Tool (BLAST) (see pg. 13, lines 272-276). In Landlinger’s study, a total of 14 genes were identified that encoded 1,4-beta-N-acetylmuramidases (see pg. 13, lines 276,-278). Landlinger discloses that the sequences all encode domain structures common to all known endolysins, including an N-terminal EAD of the glycoside hydrolase family 25 (GH25) and a CBD, comprising motifs homologous to other lysozymes (see pg. 13, line 279 to pg. 14, line 283).
Landlinger discloses that the lytic activities were tested on representatives of the four Gardnerella species, G. vaginalis, G. leopoldii, G piotti, and G. swidsinskii (see pg. 14, lines 287-291), and most of the endolysins reduced the CFU/ml of all four Gardnerella species by multiple log10 units (see pg. 14, lines 294-295). Landlinger’s discloses that this study shows that prophage-derived endolysins active on Gardnerella could be used as an innovative treatment for bacterial vaginosis, that putative endolysins can be identified in silico (see pg. 29, lines 502-504), and that wild-type endolysins identified by these methods are highly bactericidal and selective for the genus Gardnerella (see pg. 30, lines 523-524).
GenBank WP 075038579.1 is identified in GenBank as a “glycosyl hydrolase family 25” protein derived from the genome of Gardnerella vaginalis (see Title, Definition and Source). The region comprising amino acid residues 3 to 196 is explicitly identified as an “Endo-N-acetylmuramidase” lysozyme “that can degrade bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages” (see Features, “Region”). Therefore, this sequence, which can be readily found in a public database, is clearly a prophage endolysin derived from a Gardnerella vaginalis genome, as described by Landlinger. As shown in the following alignment, the GenBank sequence (bottom) comprises the full-length of instant SEQ ID NO: 3 (top):
PNG
media_image1.png
360
646
media_image1.png
Greyscale
Therefore, it would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of the aforementioned references, because Landlinger teaches that prophage endolysins derived from the genome of Gardnerella species, including those that are identified in silico (e.g., computer analysis provided by public databases), can be used to effectively treat bacterial infections caused by Gardnerella. One would have been particularly motivated to do so in order to provide an effective treatment for bacterial vaginosis that specifically targets Gardnerella species, particularly Gardnerella vaginalis. A person of ordinary skill would have recognized from Landlinger the straightforward solution of identifying similar endolysins embedded in the genome of Gardnerella vaginalis by prophages. Here, one would have recognized that the GenBank sequence is clearly identified as being analogous to the lysins of Landlinger’s disclosure, and its selection for treating infections caused by Gardnerella would have been readily apparent to an ordinary artisan. One would have also recognized from Landlinger’s study that there was a high success rate when using such wild-type endolysins to kill Gardnerella species, and, therefore, one would have had a reasonable expectation of success. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 49, Landlinger teaches the wild-type endolysins were highly bactericidal and selective for the genus Gardnerella, as discussed above.
Regarding claim 50, Landlinger teaches that prophage-derived endolysins can be used as an innovative treatment for bacterial vaginosis, as discussed above.
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 48-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-25 and 27 of copending Application No. 17/610,249 (reference application; claim set filed 06/23/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because they are anticipated by the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 48, reference claim 24 of ‘249 recites “A method of treating a Gardnerella vaginalis infection in a subject, comprising administering to the subject a therapeutically effective amount of a composition selected from the group consisting of: 1) a polypeptide comprising a hydrolase domain, the hydrolase domain comprising at least one of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, an amino acid sequence having at least 95% identity to full-length SEQ ID NO:2, an amino acid sequence having at least 95% identity to full-length SEO ID NO:3, an amino acid sequence having at least 95% identity to full-length SEQ ID NO:4, an amino acid sequence having at least 95% identity to full-length SEQ ID NO:5, and an amino acid sequence having at least 95% identity to full-length SEQ ID NO:6; 2) an isolated nucleic acid encoding the polypeptide; and 3) a vector comprising the isolated nucleic acid.” Note that SEQ ID NOs 2-6 of reference application ‘249 are identical to instant SEQ ID NOs 2-6.
Regarding the limitation of “anti-Gardnerella spp. activity”, reference claim 1 recites “A polypeptide having anti-Gardnerella spp. activity comprising a hydrolase domain” and reference claim 3 recites “The polypeptide of claim 1, wherein the hydrolase domain comprises or consists of an amino acid sequence selected from any one of SEQ ID NOs: 1 to 6 or a sequence having at least 80, 85, 90, 95, 96, 97, 98, 99, 99.5 or 100% identity thereto or a fragment thereof.” Hence, it is understood that the amino acid sequences according to SEQ ID NOs 1 to 6 of the reference application have “anti-Gardnerella spp. activity”.
Regarding instant claim 49, reference claim 25 of ‘249 recites “The method according to claim 24, wherein the composition disperses, treats, and/or decolonizes a Gardnerella vaginalis biofilm, and/or kills, or inhibits growth of, Gardnerella vaginalis.”
Regarding instant claim 50, reference claim 27 of ‘249 recites “The method according to claim 24, wherein the bacterial infection is Gardnerella vaginalis vaginosis.”
Response to Arguments
Regarding the written description rejection, Applicant argues that there is a presumption of an adequate written description, and the PTO has the initial burden of presenting evidence or reasons to the contrary. Applicant states, “although the Office Action implies that reduction to practice is required in order to fulfill the Written Description requirement, reduction to practice is not a requirement.” Applicant further argues that the application as filed provides sufficient evidence of possession, for example as evidenced by sequences, examples, and description therein. However, without prejudice to the claims, and without disclaimer of any subject matter, Applicant hereby amends independent claim 30, on which claims 48-50 depend through claim 45, to emphasize SEQ ID NOs: 5, 3, 6, 2, or 4, or a sequence having at least 95% or more identity thereto. Applicant notes that the phrase "or a fragment thereof' has been deleted from claim 30.
Applicant’s arguments have been fully considered and are persuasive with respect to claims 49-50. However, these arguments are not persuasive with respect to claim 48.
As stated in the previous office action, the polypeptides comprising hydrolases have functional requirements set forth in the claims which were not adequately described in the specification for one to correlate these functions to identify all potential structures encompassed by the claimed genus. The amendments to the claims have effectively limited the structure of the claimed hydrolases having the function of anti-Gardnerella activity and the structural variation amongst these hydrolases is reasonably limited, such that the examiner agrees that, based on the narrower functional limitations and requirements of claim 30 and 49-50, as well as the exemplification provided in Applicant’s disclosure, that these claims are presumed to have met the written description requirement in absence of evidence to the contrary.
Accordingly, the rejection of claims 49-50 are withdrawn.
However, claim 48 still requires this genus of enzymes to include those which have antibacterial effects against other bacteria, essentially encompassing a method to treat any bacterial infection. As discussed under the present invention, the specification appears to require additional structures (i.e., cell wall binding domains) in order for these polypeptides to have specificity to other bacteria. Applicant’s examples further demonstrate that polypeptides having these hydrolases are expected to have high specificity to Gardnerella, but not to other bacteria. In view of the prior art of record, it appears to be possible to achieve specificity to other bacteria (i.e., by the swapping of CBD domains from other endolysins). However, there is no consensus structure-function relationship provided by the specification, or the prior art, for one to envisage which prior art structures are included in the claimed genus. See the present rejection for further clarification regarding this issue.
In response to Applicant’s statement that “the Office Action implies that reduction to practice is required in order to fulfill the Written Description requirement”, the examiner seeks to clarify that no statement made in the rejection was intended to imply that a reduction to practice is required in every case. Per MPEP 2163, 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 inventor was in possession of the claimed genus.
In the instant case, the rejection is based not solely on the species reduced to practice, but also the disclosure of relevant, identifying characteristics, structure-function correlations, and an assessment of predictability in the art. For example, a reduction to practice of an adequate number of species may help satisfy written description when there is a lack of predictability in the art, and the lack of exemplification may be remedied by sufficient structure-function teachings. Likewise, the knowledge of the prior art may also be considered when assessing whether the written description requirement has been satisfied.
In the instant case, however, Applicant’s argument fails to provide any objective evidence regarding any of these factors that the examiner may consider for overcoming the rejection. Accordingly, the rejection of claim 48 is maintained.
Regarding the scope of enablement rejection under 35 U.S.C. 112(a), Applicant states that claim 48 has been amended to delete the term “preventing” and submits that the claims are enabled.
Applicant’s arguments have been fully considered and they are persuasive.
The previous Office Action set forth the conclusion that the claims were not enabled for a method for “preventing” a bacterial infection, because this would require an undue amount of experimentation to make and use the full scope of the claimed invention. Considering the amendment to claim 48, this rejection is withdrawn.
Regarding the rejections under 35 U.S.C. 102 in view of Corsini, Applicant states that independent claim 30 has been amended to delete reference to SEQ ID NO: 1.
Applicant’s arguments have been fully considered and are persuasive.
Corsini does not appear to teach SEQ ID NOs 2-6. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection under 35 U.S.C. 103 is made in further view of Landlinger and GenBank WP 075038579.1, as necessitated by Applicant’s amendment.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS ARMATO whose telephone number is (703)756-5348. The examiner can normally be reached Mon-Fri 11:00am-7:30pm EST.
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, Melenie Gordon can be reached at (571) 272-8037. 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.
/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
Prosecution Insights