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 1-2, 5 and 8-10 are pending in the instant application. Claims 3-4 and 6-7 are newly cancelled. Claims 1 and 8-10 are withdrawn.
Claims 2 and 5 are under examination herein.
The objection to claim 2 is withdrawn in light of the amendment making the genus species format consistent for all species.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/27/2025 has been entered.
Priority
This application is a 371 of PCT/SE2020/050290 filed on 3/19/2020, which claims priority to SWEDEN 1950356-4 filed on 3/21/2019. Receipt is acknowledged of certified copies of papers in English required by 37 CFR 1.55.
The effective filing date for the application is March 21, 2019.
Claim Rejections - 35 USC § 112
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.
Claims 2 and 5 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
Applicant is referred to MPEP 2163(II)(A)(3)(a)(i and ii), which states that 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. 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. 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 genus. 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.
Claims 2 and 5 are drawn to an isolated protein having an amino acid sequence according to SEQ ID NO:2. The claims require “having an amino acid sequence identity of at least 60% to SEQ ID NO:2 and having at least 80% of the DNase activity of the protein according to SEQ ID NO:2”. The specification does not disclose a representative number of functional variants that meet the required functional limitation of at least 80% of the DNase activity of the protein according to SEQ ID NO:2.
The current specification describes an isolated protein having the amino acid sequence according to SEQ ID NO:2 that has DNase activity (specification p.9, lines 25-27). The specification identifies that functional variants may be assessed for retained DNase activity at pH 7 and 32°C or at pH 6 and 25°C (specification p.9 line 34 – p.10, line 1). The specification states that such variants may be made using methods of protein engineering and site-directed mutagenesis which are well known in the art (specification p.10, lines 13-14). The specification further identifies that PG_1116 is a predicted protein of 939 amino acids (SEQ ID NO:2) that contains a DNase I domain, a TAT protein, a YhcR-OBF domain that could be important for recognition of specific patterns and a non-specific fungal domain of unknown function (specification p.18, lines 18-26).
The specification does not provide any guidance on the structure-function relationship of SEQ ID NO:2, does not provide any information on which amino acids can be varied or deleted while preserving the DNase function of the protein, nor any guidance on which amino acid residues of SEQ ID NO:2 are critical to determine what other proteins having an amino acid sequence identity of at least 60% to SEQ ID NO:2 and having a least 80% of the DNase activity of the protein according to SEQ ID NO:2. Based on the lack of art-recognized structure-function relationship of SEQ ID NO:2 to other functional variants, it is highly unpredictable as to what other proteins of at least 60% identity to SEQ ID NO:2 would provide the instantly recited function.
The disclosure of a single species of a protein having an amino acid sequence according to SEQ ID NO:2 and having DNase activity is not considered to constitute a representative number of species of the genus of proteins having an amino acid sequence identity of at least 60% to SEQ ID NO:2 and having a least 80% of the DNase activity of the protein according to SEQ ID NO:2, in view of the lack of any guidance as to which proteins having at least 60% amino acid identity to SEQ ID NO:2 will also have at least 80% DNase activity of the protein. Thus, one of ordinary skill in the art could not conclude that Applicant was in possession of any species of the claimed genus of proteins comprising an amino acid sequence identity of at least 60% to SEQ ID NO:2 and having a least 80% of the DNase activity of the protein according to SEQ ID NO:2., as no functional variants are disclosed in the specification. This disclosure does not constitute a representative number of species of the genus in view of the potential breadth and variability in the genus, and so there is a failure to satisfy the written description requirement for the genus.
Response to Arguments
Applicant argues that the written description rejection should be withdrawn because previous amendments narrowed the scope of the pending claims, and arguments and evidence previously presented in the amendment filed March 24, 2025 (See Remarks dated 10/27/25, p.4 last paragraph). Applicant argues that multiple examples support the narrowed scope of the amended claims and submitted Exhibit A is a report showing that the present invention is effected for biofilms formed by bacteria or fungi other than P. acnes (See Remarks dated 10/27/25, p.4 last paragraph). Applicant argues that the pending claims recite a narrower scope of coverage wherein the functional variants have a sequence identity of at least 60^ to SEQ ID NO:2 and at least 80% of the DNase activity of the protein according to SEQ ID NO:2, and those of ordinary skill in the art would know how to construct a protein that is up to 40% different from SEQ ID NO:2 and which has at least 80% DNase activity of SEQ ID NO:2 using standard technology in the field (See Remarks dated 10/27/25, p.5 1st full paragraph). Applicant reiterates previously presented arguments regarding modeling analysis of the protein structure with primary SEQ ID NO:2; identity of two domains called NTD and CTD; and argues that as one of ordinary skill in the art would have access to the above mentioned databases and methods, it would be well within their skill to determine how to produce variants of the protein with at least 60% identity and at least 80% DNase activity of the protein with SEQ ID NO:2 (See Remarks dated 10/27/25, p.5 – p.7 1st paragraph).
Applicant's arguments filed October 27, 2025 have been fully considered but they are not persuasive. The 112(a) written description rejection is based on whether one can truly ascertain that applicant was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams and formulas that fully set forth the claimed invention. A protein having 60% sequence homology to SEQ ID NO:2 permits 375 amino acids that can be altered. Assuming a single amino acid substitution, that is 20 possible amino acids in 375 possible locations, which results in 7512 possible different sequences. If more than one amino acid is substituted, the possible number of sequences becomes exponentially larger. There is only one example in the specification that is reduced to practice. As discussed in the rejection above, the specification does not provide any guidance on the structure-function relationship of SEQ ID NO:2; does not provide any information on which amino acids can be varied or deleted while preserving the DNase function of the protein, nor provide any guidance on which amino acid residues of SEQ ID NO:2 are critical to determine what other proteins having an amino acid sequence identity of at least 60% to SEQ ID NO:2 and having a least 80% of the DNase activity of the protein according to SEQ ID NO:2. Based on the lack of art-recognized structure-function relationship of SEQ ID NO:2 to other functional variants, it is highly unpredictable as to what other proteins of at least 60% identity to SEQ ID NO:2 would provide the instantly recited function. Thus, the unexpected results are not commensurate in scope with the claimed invention. See MPEP §716.02(b) which states "The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992)”, and MPEP §716.02(d) which states “the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range”.
Applicant’s arguments regarding the availability of various databases and tools provide methods of enabling one of ordinary skill in the art to perform various analyses on SEQ ID NO:2; however they do not address the lack of description of the claimed invention regarding the genus of “functional variants”.
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.
Claims 2 and 5 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 2 recites “an isolated protein having an amino acid sequence according to SEQ ID NO:2 having an amino acid sequence identity of at least 60% to SEQ ID NO:2 and having at least 80% of the DNase activity of the protein according to SEQ ID NO:2 in a quantitative assay of deoxyribonuclease activity at pH 7 and 32°C to a subject in need thereof”. It is unclear whether the isolated protein is required to have an amino acid sequence of 100% identity to SEQ ID NO:2 or sequence identity of at least 60% to SEQ ID NO:2. It is further unclear what the phrase “having at least 80% of the DNase activity of the protein according to SEQ ID NO:2” is modifying.
This rejection can be obviated by deleting the limitation underlined above and amending claim 2 to recite having the amino acid sequence of SEQ ID NO:2.
Claim Rejections - 35 USC § 103
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.
Claims 2 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Burgess et al. (WO 2011/098579 A1, published on August 18, 2011; previously cited) in view of GenBank reference corresponding to accession number ERF66724.1 and deposited on September 4, 2013; previously cited.
Regarding claim 2, Burgess teaches compounds, compositions and methods for biofilm disruption and prevention (abstract). Burgess teaches the pharmaceutical formulations comprising the microbial deoxyribonuclease compositions can be administered inter alia intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavity, orally and by inhalation (relevant to biofilm-forming bacteria; relevant to administering an isolated protein having DNase activity) (description p.12, [0072]). Burgess teaches a method of disrupting a biofilm on a patient comprising contacting a biofilm on a patient with any of the pharmaceutical compositions described herein (relevant to a method for treatment comprising administering to a subject in need thereof) (description p.8, [0039]). Burgess further teaches a method of preventing the formation of a biofilm on a patient comprising contacting a surface of a patient susceptible to biofilm formation with any of the pharmaceutical compositions described herein (relevant to a method of prevention comprising administering to a subject in need thereof) (description p.8, [0040]). Burgess teaches isolated microbial deoxyribonuclease polypeptides for use as a pharmaceutical, wherein said use is in the treatment of infections of the skin (description p.47, claim 19). Burgess teaches that the microbial deoxyribonuclease pharmaceutical compositions can affect bacteria including Staphylococcus aureus, Staphylococcus pyogenes, Streptococcus sp., Streptococcus pneumoniae, Enterococcus sp., Propionibacterium acnes, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Campylobacter jejuni ([00113]); Candida albicans ([00114]); Aspergillus fumigatus ([00114]); Haemophilus influenzae ([00115]; Staph. epidermidis ([00115]); Acinetobacter sp. ([00155]); Staphylococcus sp. ([00155]); Bacillus licheniformis ([00159]); Micrococcus sp. ([00168]); Bacillus subtilis ([00168]); and biofilms derived from Vibrio sp. ([00206]).
Burgess is silent as to whether the microbial deoxyribonuclease has at least 60% homology to instant SEQ ID NO:2.
GenBank teaches a putative extracellular nuclease isolated from Cutibacterium granulosum TM11 that has 94% homology to instant SEQ ID NO:2 (GenBank reference with accession number ERF66724.1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Burgess to replace the microbial deoxyribonuclease taught by Burgess with the nuclease having 94% homology with instant SEQ ID NO:2 taught by GenBank to arrive at the claimed invention. Both Burgess and GenBank teach nucleases. One of ordinary skill in the art would have a reasonable expectation of success that replacing the microbial deoxyribonuclease taught by Burgess with the nuclease taught by GenBank with 94% homology with instant SEQ ID NO:2 would predictably result in an isolated protein having at least 80% of the DNase activity of the protein according to SEQ ID NO:2, because the sequence taught by GenBank has 94% homology to instant SEQ ID NO:2, and it was known in the art at the time of invention that microbial deoxyribonucleases could be used to disrupt biofilms.
Regarding claim 5, Burgess teaches infection with one or more bacteria can result in diseases such as acne and impetigo (description p.22, [00113]).
Response to Arguments
Regarding the §103 rejection of claims 2 and 5: Applicant argues that Burgess discusses the use of microbial deoxyribonucleases, but does not disclose the isolated protein of amended claim 2 (See Remarks dated 10/27/25, p.7 3rd paragraph). Applicant argues that the microbial deoxyribonuclease taught by Burgess has only 5% identity with instant SEQ ID NO:2 and very few amino acids that could have similar properties (8%) (See Remarks dated 10/27/25, p.7 3rd paragraph). Applicant argues that submitted Exhibits A and B provide data that shows comparisons of DNase activity of proteins within and outside the claim limitations; proteins with greater than 60% sequence homology to SEQ ID NO:2 can effectively degrade DNA while proteins having less homology do not have that ability (See Remarks dated 10/27/25, p.7 last paragraph to p.8 top paragraph).
Applicant's arguments filed October 27, 2025 have been fully considered but they are not persuasive. Burgess is relied upon to teach the active method steps of administering an isolated protein having DNase activity for treatment and/or prevention of a disease of the skin caused or complicated by infections of one or more biofilm-forming bacteria selected from Staphylococcus aureus, Staphylococcus pyogenes, Streptococcus sp., Streptococcus pneumoniae, Enterococcus sp., Propionibacterium acnes, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Campylobacter jejuni ([00113]); Candida albicans ([00114]); Aspergillus fumigatus ([00114]); Haemophilus influenzae ([00115]; Staph. epidermidis ([00115]); Acinetobacter sp. ([00155]); Staphylococcus sp. ([00155]); Bacillus licheniformis ([00159]); Micrococcus sp. ([00168]); Bacillus subtilis ([00168]); and biofilms derived from Vibrio sp. ([00206]). Burgess is not relied upon to teach instant SEQ ID NO:2. GenBank teaches an amino acid sequence of a nuclease with 94% homology to instant SEQ ID NO:2. One of ordinary skill in the art would have found it obvious to use a protein having DNase activity to treat a disease of the skin based on the teachings of Burgess. One of ordinary skill in the art would have reasonably expected that replacing the microbial deoxyribonuclease taught by Burgess with the nuclease taught by GenBank would predictably result in an isolated protein having an amino acid sequence having an amino acid sequence identity of 94% to instant SEQ ID NO:2, and therefore also have at least 80% of the DNase activity due to the sequence homology.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/DEEPA MISHRA/Examiner, Art Unit 1657