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 .
Claims Status
Claims 1-17 is/are cancelled and claims 18-37 is/are newly added. Claims 18-37 is/are currently pending. Claims 18-37 is/are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/19/2022 has been considered; the examiner has annotated NPL #24 (Karberg et al.) to indicate that while the title as listed in the IDS does not match the title of the Karberg et al. reference copy provided by the applicant (and, instead, the title of NPL #24 as listed in the IDS appears to be a duplicate of the title of NPL #23, Jung et al.), all other identifying details (author, journal title, year, volume, page numbers) match the Karberg et al. article copy provided, titled “Group II Introns as Controllable Gene Targeting Vectors for Genetic Manipulation of Bacteria”, and the examiner has considered this reference, as indicated.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 23 and 32 are objected to because of the following informalities: “antibiotic resistance bacteria” should read “antibiotic-resistant bacteria”. Appropriate correction is required.
Claims 24 and 34 are objected to because of the following informalities: for clear, consistent phrasing and syntax, lines 2-3 of these claims should read either “before the subject or patient undergoes surgery and/or cancer treatment and/or immunosuppressive treatment” or “before the subject or patient undergoes surgery and/or undergoes cancer treatment and/or undergoes immunosuppressive treatment”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
112(b):
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.
Claim 28, 30-31, 34, 36-37 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 28 and 34 recite the limitation "the nuclease" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 18, which claim 28 depends on, and claim 19, which claim 34 depends on, do not recite the limitation “a nuclease”; as such, it is not clear what limitation “the nuclease” of claims 28 and 34 refers to.
Regarding claims 30 and 36, the term "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 31 and 37, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Written Description:
Claims 18-27, 29-33, 35-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
Claims 18 and 19 recite the limitation that the methods comprise administering a “DNA-modifying enzyme”, and claims 20 and 21 recite the limitations that the enzyme is a nuclease (claim 20) or a base editor (claim 21). The specification does not provide support for the full scope of these limitations. The specification describes specifically CRISPR-associated nucleases, ZFNs, TAL effector nucleases, and meganucleases (paragraph [0109]), or Cas-ADAR fusion proteins (paragraph 0170]). While CRISPR-associated nucleases, ZFNs, TAL effector nucleases, and meganucleases are examples of nucleases, and Cas-ADAR fusion proteins are examples of base editors, these are not representative of the full scope of the genera of DNA-modifying enzymes, nucleases, and base editors, and these genera encompass many different types of enzymes in addition to these. Furthermore, the specification does not describe additional DNA-modifying enzymes, nucleases, or base editors by any other relevant identifying characteristics, specific features, or functional attributes which would distinguish different members of the claimed genera. The only additional functional attribute is that the enzyme is capable of inactivating an antibiotic resistance gene (claims 18-19); however, it cannot be determined based on the disclosure which species of the claimed genera are or are not capable of fulfilling this functional limitation, and as such, this functional attribute does not sufficiently describe the claimed genera of enzymes. Dependent claims 22-27, 29-33, and 35-37 do not provide further limitations which sufficiently describe these genera.
According to the 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 (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. 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 Deutsch land 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.")."
Claims 18-27, 29-33, 35-37 and the disclosure fail to sufficiently, fully describe the genera of DNA-modifying enzymes, nucleases, and base editors created by claims 18-21; the claims and disclosure provide a limited number of species of these genera which are not representative of the full scope of species encompassed by these genera. Dependent claims 22-27, 29-33, and 35-37 do not provide further limitations which sufficiently describe these genera. As such, claims 18-27, 29-33, and 35-37 are not sufficiently described in their entirety and are rejected under 35 USC 112(a) for failing to fulfill the written description requirement.
Scope of Enablement:
Claims 18-37 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 in vivo methods in non-human animals and for the use of CRISPR nucleases in the claimed methods, does not reasonably provide enablement for in vivo methods in human subjects nor for the use of any DNA-modifying enzyme in the claimed methods. 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.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims:
With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. As such, the broadest reasonable interpretation of the claimed method is that it encompasses administration to subjects or patients of any species, including humans, any DNA-modifying enzyme. A skilled artisan would not know how to use the method with a reasonable expectation of success based solely on what is disclosed in the specification.
The amount of direction provided by the inventor and the level of predictability in the art:
The specification teaches that “animal experiments can provide reliable guidance for the determination of effective doses in human therapy” (paragraph [0362]), and that the subject or patient of the claimed methods can be a human (paragraphs [0365]-[0366]). The art at the time of filing, however, taught that the safety and efficacy of methods of removing antibiotic resistance from a microbiome, including intestinal microbiome, using genome editing tools in humans was an active and new field of study; as such, a method with demonstrable therapeutic benefit in animal models could not be assumed to be effective in human subjects (Vila, 2018; Furfaro, 2018). The specification as filed does not provide guidance that overcomes this unpredictability within the art.
The specification provides a description of DNA-modifying enzymes which are nucleases, specifically CRISPR-associated nucleases, ZFNs, TAL effector nucleases, and meganucleases (paragraph [0109]), or Cas-ADAR fusion proteins (paragraph 0170]). However, the specification does not describe any other DNA-modifying enzyme nor how any other class of DNA-modifying enzyme could or could not be used in the methods. Given this, a person of ordinary skill in the art would not be able to determine how to use any DNA-modifying enzyme that is not a CRISPR-associated nuclease, ZFN, TAL effector nuclease, meganuclease, or a Cas-ADAR fusion protein in the claimed methods with a reasonable assumption of success.
The existence of working examples:
What is enabled by the working examples is narrow in comparison to the breadth of the claims: The specification discloses the use of the claimed methods in mice in vivo (paragraphs [0400]-[0405]); however, no working examples of use of the claimed methods in humans are present in the disclosure. Furthermore, the specification discloses the use of CRISPR-associated nucleases (Fn Cpf1, paragraphs [0391], [0402]) in working examples; the specification does not disclose working examples wherein other DNA-modifying enzymes are used to edit an antibiotic resistance gene.
The quantity of experimentation needed to make or use the invention:
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution. Given that the nature of the invention is in vivo elimination of antibiotic resistance in microbiota of a subject of any species using any DNA-modifying enzyme, a person having ordinary skill in the art would have to perform multiple further experiments in human clinical trials—and in representative animal models and in vitro cell culture with non-CRISPR-associated nucleases—in order to demonstrate the invention could be used with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the method with a reasonable expectation of successfully treating any CNS disorder or neurodegenerative disease. Therefore, Claims 18-37 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement.
Claim Rejections - 35 USC § 102
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) 18-20, 23, 26-29, 30-32, 34-36 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clube (WO2016177682A1).
Regarding claims 18-19, Clube teaches a method for selectively removing antibiotic resistance from an antibiotic-resistant bacterial strain(s) in a subject and thereby also preventing antibiotic resistance-related infection in a subject, the method comprising administering to the subject at least one vector encoding a DNA-modifying enzyme inactivating the antibiotic resistance gene(s) responsible for the antibiotic resistance of the bacterial strain(s) (claims 1-6, 10).
Regarding claims 20, 28, and 34, Clube teaches that the DNA-modifying enzyme is a CRISPR-associated nuclease (claims 1-2).
Regarding claims 23, 26, and 32, Clube teaches that antibiotic-resistant bacteria are removed from the gut of the subject (claim 6).
Regarding claims 29 and 35, Clube teaches that the identification of the bacterial species in a mixed population of bacteria to be modified by the taught methods is essential (page 168, 172). Clube also teaches medical applications of the methods, wherein the pathogenic bacterial strain in the subject is known prior to treatment, requiring testing to identify the pathogenic bacterial strain (pages 157-158).
Regarding claim 27, Clube teaches that the antibiotic resistance gene confers resistance to methicillin, vancomycin, or a carbapenem or beta-lactam class antibiotic (pages 139-140).
Regarding claims 30 and 36, Clube teaches that at least two distinct vectors or recombinant phages are administered, each vector or phage encoding a DNA modifying enzyme targeting a different nucleic acid sequence inside the targeted bacteria (claims 14-20).
Regarding claim 31, Clube teaches that the method can be used in a subject suffering from cancer and undergoing cancer treatment (page 25).
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 18 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Clube (WO2016177682A1), and further in view of Sun (2019).
Regarding claim 18, Clube teaches a method for selectively removing antibiotic resistance from an antibiotic-resistant bacterial strain(s) in a subject and thereby also preventing antibiotic resistance-related infection in a subject, the method comprising administering to the subject at least one vector encoding a DNA-modifying enzyme inactivating the antibiotic resistance gene(s) responsible for the antibiotic resistance of the bacterial strain(s) (claims 1-6, 10).
However, Clube does not teach that the DNA-modifying enzyme is a base editor.
Sun teaches that base editors can be used to edit antibiotic resistance genes.
Regarding claim 21, Sun teaches a method of using a base editor (pBECKP-spe of AddGene plasmid number 117236, an Sp-nCas9-rAPOBEC1 fusion) to inactivate an antibiotic resistance gene (pages 2, 4).
The teachings of Sun would have rendered obvious to a person of ordinary skill in the art at the time of filing that a base editor, such as pBECKP-spe, could be substituted for a CRISPR-associated nuclease in a method of eliminating or inactivating an antibiotic resistance gene in a bacterium, as taught by Clube, as both a CRISPR-associated nuclease and a base editor, through different mechanisms, can each effectively inactivate an antibiotic resistance gene.
Claim(s) 18 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Clube (WO2016177682A1) as applied to claim 18 above, and further in view of Soubrier (1999).
The teachings of Clube are discussed above and render obvious the limitations of claim 18. However, Cube does not teach the use of a conditional origin of replication which is inactive in the targeted antibiotic-resistant bacterial strain(s) but is active in a donor bacterial cell.
Soubrier teaches a conditional origin of replication, which is only active in a donor bacterial cell and not active in any other cell (see Abstract; see full document).
Soubrier teaches that a conditional origin of replication (COR) increases safety of gene therapy, as it prevents propagation of the vector comprising the COR in the environment and in patients, while still enabling expression of encoded proteins in cells which cannot propagate the vector (see Abstract; see full document). It would have been obvious to a person of ordinary skill in the art at the time of filing that the safety of the vectors of Clube could be improved by replacing the origin of replication of the vectors of Clube with the conditional origin of replication taught by Soubrier.
Claim(s) 18-19, 24-25, 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Clube (WO2016177682A1) as applied to claim 18 above, and further in view of Bisson (2018).
Regarding claims 18-19, Clube teaches a method for selectively removing antibiotic resistance from an antibiotic-resistant bacterial strain(s) in a subject and thereby also preventing antibiotic resistance-related infection in a subject, the method comprising administering to the subject at least one vector encoding a DNA-modifying enzyme inactivating the antibiotic resistance gene(s) responsible for the antibiotic resistance of the bacterial strain(s) (claims 1-6, 10).
However, Clube does not teach that the method is performed prior to a surgery, a cancer treatment, or an immunosuppressive treatment.
Bisson teaches that antibiotic-resistant infection post-cancer treatment is a major concern in veterinary medicine.
Regarding claims 24 and 33, Bisson teaches that prophylactic antibiotic therapy prior to surgery or cancer therapy (chemotherapy) is a useful tool for preventing infection in a vulnerable population (animals undergoing surgical or chemotherapeutic therapies); however, caution must be exerted, as antibiotic administration in an animal colonized with antibiotic-resistant bacteria can result in proliferation of and infection by antibiotic-resistant bacteria (pages 301-304).
Regarding claim 25, the limitations of claim 25 merely require that if the subject or patient undergoes surgery, the surgery is a solid organ transplant surgery of the kidney or liver, but claim 25 does not require that the patient or subject undergoes surgery; as such, the limitations of claim 25 are interpreted to be optional. Bisson broadly refers to veterinary surgery, which encompasses any type of surgery including solid organ transplants, but does not specifically refer to kidney or liver transplants. However, as all of claim 25 is considered optional because of the specific phrasing of the claim, Bisson does not need to teach the limitations of claim 25.
The teachings of Bisson render obvious that methods for eliminating antibiotic resistance genes in a veterinary patient’s microbiome prior to surgery or chemotherapy would allow for greater use of antibiotic prophylaxis, preventing more cases of post-surgical or -chemotherapeutic bacterial infections. As such, Bisson renders obvious to a person of ordinary skill in the art at the time of filing that the methods taught by Clube should be performed in animals prior to surgical or chemotherapeutic therapies, thereby eliminating antibiotic resistances in microbiota bacteria in the patient and enabling antibiotic prophylaxis therapy, thereby preventing post-therapeutic bacterial infections and reducing post-therapeutic complications and mortality.
Claim(s) 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Clube (WO2016177682A1), in view of Bisson (2018).
Regarding claim 37, Clube teaches a method for preventing antibiotic resistance-related infection in a subject, the method comprising administering to the subject at least one recombinant phage encoding a DNA-modifying enzyme inactivating the antibiotic resistance gene(s) responsible for the antibiotic resistance of the bacterial strain(s) (claims 1-6, 10, 14, 18). Clube teaches methods in which multiple vectors or phages are administered to the subject, wherein the vectors each encode multiple gRNAs which target different nucleic acid sequences (page 157). Furthermore, Clube teaches that the methods comprise administering three or more (“more than three” encompasses at least four) recombinant phages (claims 18-20). Clube teaches that the methods are used to eliminate antibiotic resistance gene expression in E. coli strains in the microbiome, combined with antibiotic therapy to prevent or treat bacterial infection (claims 22-23, 26-27, 34-35).
However, Clube does not disclose the utility of the taught methods in patients suffering from a hematological malignancy.
Bisson teaches that antibiotic-resistant E. coli infection is a concern in patients suffering from hematological malignancies.
Regarding claim 37, Bisson teaches that antibiotic-resistant E. coli infection in the bloodstream is a concern in veterinary patients suffering from a hematological malignancy (see page 303).
Given the teachings of Bisson, it would have been obvious to a person of ordinary skill in the art at the time of filing that the methods of Clube would be beneficial to use in veterinary lymphoma patients in order to reduce the risks of antibiotic-resistant E. coli infection, and that such a combination would be feasible as the recombinant phages of Clube can be used to target specifically E. coli cells and can be administered intravenously (page 26).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/RAM R SHUKLA/ Supervisory Patent Examiner, Art Unit 1635