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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 dated 11/20/2025 has been entered pursuant to RCE filed on 11/20/2025.
Pursuant to the amendment dated 11/20/2025, claims 2, 4-9, 12-14, and 16-19 are cancelled, claims 1 and 15 are amended, and claims 30-31 are newly added. Claims 1, 3, 10, 11, 15, and 20-31 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/EP2020/086511 filed on 12/16/2020 and claims foreign priority to EPO 19216548.8 filed on 12/16/2019.
New and Maintained Rejections
Claim Rejections - 35 USC § 102
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.
Claims 1 and 23-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pruteanu et al (EP 3524237 A1, published 08/14/2019, see IDS dated 11/06/2022).
Pruteanu is drawn to the repurposing of compounds for the treatment of infections and for modulating the composition of the gut microbiome (title). Pruteanu teaches that dicumarol is a compound for use in the modification of the growth of bacterial cells (claim 1).
It is noted that the prior art does not exemplify the compound can be used in the manner instantly claimed, for antagonizing a first bacterium that is a commensal species and not antagonizing the antibacterial effect of at least one macrolide antibiotic on a second bacterium that is a pathogenic bacterium. However, the cited recitations are considered an “intended use” of the claimed compound. The “intended use” of the claimed compound does not patentably distinguish the compound, per se, since the compound would be capable of performing the intended use. In order to be limiting, the intended use must create a structural difference between the claimed compound and the prior art compound. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Regarding claims 23-25, they further limit the intended use and do not add any structural limitations to the claimed compound of dicumarol.
Accordingly, the instant claims are anticipated by the teachings of the prior art.
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.
Claims 1, 3, 10, 11, 23-26, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Collins et al (US 2015/0071904 A1, published 03/12/2015, see PTO-892).
Collins is drawn to compositions and methods comprising reactive oxygen species (ROS) target modulators that increase ROS flux and endogenous ROS production, thereby potentiating oxidate attack by antibiotics and biocides (abstract). Collins teachings that ROS production can be predictably enhanced in bacteria thereby increasing the bacteria’s susceptibility to oxidative attack. Collins created a model capable of predicting ROS production in E. coli and other bacteria. The metabolic network models were systematically perturbed and flux distributions analyzed to identify targets predicted to increase ROS production (paragraph 0005). Collins teaches a method for inhibiting a bacterial infection by increasing ROS production in a bacteria, the method comprising administering to a subject having or at risk for a bacterial infection an effective amount of a pharmaceutical composition comprising one or more ROS target modulator compounds and an antibiotic agent (paragraph 0007). A ROS target modulator compound could be an inhibitor of NADH dehydrogenase such as dicumarol (paragraph 0014). Any of the major classes of antibiotic agents in which bactericidal activity is potentiated or enhanced by inhibiting ROS production can be used with the ROS target modulators such as erythromycin (paragraph 0200). Therapeutic formulations of one or more ROS target modulator compounds with/without an antibiotic agent can be prepared by mixing an antibiotic agent and/or ROS target modulator compound having the desired degree of purity with one or more pharmaceutically acceptable carriers, excipients or stabilizers (paragraph 0302). The pharmaceutical composition may be administered as tablets and capsules in which case solid pharmaceutical excipients are used. The tablets can be coated (paragraph 0313). The composition may be administered as an inhalation mixture (paragraph 0324). Other examples of administration are creams, ointments, and lozenges (paragraph 0306).
Collins does not exemplify a composition containing both dicumarol and erythromycin.
It would have been prima facie obvious to select a composition comprising both dicumarol and erythromycin before the effective filing date of the claimed invention to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select a composition containing both dicumarol and erythromycin because Collins teaches a pharmaceutical composition containing both a ROS target modulator and an antibiotic in which the bactericidal activity is enhanced by ROS production. One of ordinary skill in the art would have a reasonable expectation of success because Collins further teaches that dicumarol is a ROS target modulator and erythromycin is an antibiotic in which the bactericidal activity is enhanced by ROS production.
Regarding claims 1, 3, 10, 23, and 24, it is noted that the prior art does not exemplify the composition can be used in the manner instantly claimed, for antagonizing a first bacterium that is a commensal species and not antagonizing the antibacterial effect of at least one macrolide antibiotic on a second bacterium that is a pathogenic bacterium. However, the cited recitations are considered an “intended use” of the claimed composition. The “intended use” of the claimed composition does not patentably distinguish the composition, per se, since the composition would be capable of performing the intended use. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Claims 15, 20-22, 27-29 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Pruteanu et al (EP 3524237 A1, published 08/14/2019, see IDS dated 11/06/2022) and Collins et al (US 2015/0071904 A1, published 03/12/2015, see PTO-892).
Pruteanu is drawn to the repurposing of compounds for the treatment of infections and for modulating the composition of the gut microbiome (title). Pruteanu teaches that dicumarol is a compound for use in the modification of the growth of bacterial cells (claim 1). The bacterial cells are selected from Gram-positive bacteria, Gram-negative bacteria, Streptococcus, Staphylococcus, and Bacteroides (claim 2). The dicumarol may be administered to a human to modify the growth of bacterial cells in said subject wherein modifying the growth of bacterial cells results in the prevention and/or treatment of a disease (claim 3). Pruteanu teaches that the disease may be dysbiosis (claim 4). Pruteanu teaches that dicumarol may be used in a pharmaceutical composition for use in the prevention and/or treatment of a disease in a subject and/or in the modification of the composition of the microbiome of subject. The pharmaceutical composition may also contain a pharmaceutically acceptable additive, carrier, diluent, solvent, filter, lubricant, excipient, binder, and/or stabilizer (claim 14). Pruteanu tested the inhibitory effect of dicumarol and found that it was not specifically inhibitory to P. vulgatus and was inhibitory to streptococcus parasanguinis and streptococcus salivarius (Table 7, page 36).
Pruteanu does not teach the combined administration of dicumarol and a macrolide. Pruteanu does not teach the specific pathogenic bacterium S. aureus or S. pneumoniae as recited in claim 25. Pruteanu does not teach the functional limitation of dicumarol antagonizing an antibacterial effect of a macrolide in a commensal species and not antagonizing the macrolide antibacterial effect on a pathogenic species.
The teachings of Collins are discussed above.
Collins further teaches the bacterial infection involves one or more of E. coli, Streptococcus pneumoniae, or Staphylococcus aureus (paragraph 0052). One of the key advantages of the method, uses and compositions of Collins is the ability of producing marked anti-bacterial effects in a human subject having a bacterial infection and thereby increasing bacterial sensitivity and susceptibility to a variety of antibiotic classes, as well as reducing toxicities and adverse effects. In some embodiments the dosage of the antibiotic administered may be reduced relative to the normally administered dosage (paragraph 0294).
It would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Pruteanu and Collins before the effective filing date of the claimed invention by modifying the method for treating dysbiosis with a composition containing dicumarol taught by Pruteanu to also co-administer erythromycin as taught by Collins to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the method for treating dysbiosis with a composition containing dicumarol taught by Pruteanu by co-administering erythromycin because Collins teaches the co-administration of dicumarol and erythromycin for improved anti-bacterial effect. One of ordinary skill in the art would have a reasonable expectation of success because Pruteanu teaches that dicumarol may be used to treat dysbiosis and can inhibit Streptococcus and Staphylococcus, which are pathogenic bacteria, but not inhibit P. vulgatus, which is a commensal bacteria, and Collins teaches that dicumarol may be used to improve the anti-bacterial effect of erythromycin towards the pathogenic bacterium S. aureus or S. pneumoniae. Additionally, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Therefore, although the functional limitation is not directly taught by Pruteanu or Collins, the combination of Pruteanu and Collins suggests that the combination of dicumarol and erythromycin to treat abnormalities in the gut microbiome, such as dysbiosis. The administration of the combination would naturally lead to the claimed results arising from the structural properties of dicumarol and erythromycin.
Response to Arguments
Applicant's arguments filed 11/20/2025 have been fully considered but they are not persuasive.
Regarding the rejection of claims 1 and 23-25 under 35 U.S.C. 102(a)(1) as being anticipated by Pruteanu, applicant argues that Pruteanu does not anticipate all the limitations of instant claims 1 and 23-25 such as dicumarol’s use in treating dysbiosis and for use in antagonizing the antibacterial effect of at least one macrolide antibiotic in at least one bacterium selected from commensal species and not antagonizing the antibacterial effect of the at least one macrolide antibiotic in at least one second bacterium selected from pathogenic bacteria. The argument is not persuasive. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The intended use limitations of instant claims 1 and 23-25 do not structurally limit the compound, dicumarol. As Pruteanu discloses dicumarol, it therefore anticipates instant claims 1 and 23-25.
Regarding the rejection of claims 1, 3, 10, 11, 23-25, and 26 under 35 U.S.C. §103 as being unpatentable over Collins, applicant argues that Collins teaches dicumarol and erythromycin from a large number of ROS target modulators and antibiotics, respectively, and therefore, one of ordinary skill in the art would have no reason to specifically select dicumarol and erythromycin out of the respective lists of ROS target modulators and antibiotic agents for combination. Applicant also argues that Collins does not teach the mode of action of dicumarol and erythromycin for antagonizing the antibacterial effect of erythromycin in a commensal species and not antagonizing the antibacterial effect of erythromycin in a pathogenic bacterium. The argument is not persuasive. Collins teaches the method of inhibiting a bacterial infection comprising administering to a subject a pharmaceutical composition comprising a ROS target modulator and antibiotic agent and further teaches that the target modulator can be dicumarol and the antibiotic can be erythromycin. Although Collins does not exemplify the compounds dicumarol and erythromycin, Collins teaches a finite list that explicitly discloses dicumarol as a target modulator and erythromycin as an antibiotic. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solution of compounds that can be administered with a reasonable expectation of success. Regarding the mode of action, the instant claims 1, 3, 10, 11, 23-25, and 26 are compound and composition claims, therefore the intended use is not limiting. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding the rection of instant claims 15, 20-22, and 27-29 under 35 U.S.C. §103 as being unpatentable over Pruteanu and Collins, applicant argues that Pruteanu does not teach the combined administration of dicumarol and a macrolide for use in treating dysbiosis, wherein dicumarol antagonizes the antibacterial effect of the macrolide antibiotic in a commensal species and does not antagonize the antibacterial effect of the macrolide antibiotic in a pathogenic bacterium. Applicant further argues that Collins does not cure the deficiency of Pruteanu. The argument is not persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Pruteanu teaches that dicumarol may be used to tread dysbiosis and Collins teaches that a macrolide such as erythromycin antibacterial effect may be enhanced by inhibiting ROS production with a compound such as dicumarol. Therefore, it would be obvious to one of ordinary skill in the art to combine the administration of erythromycin and dicumarol for the treatment of dysbiosis.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA LYNN SCHACHERMEYER whose telephone number is (703)756-5337. The examiner can normally be reached Monday thru Friday, alternate Fridays off, 7:30AM-5PM 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, Scarlett Goon can be reached on (571) 270-5241. 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.
/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693 /SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693