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, 3-8, 10-16 and 18-22 are pending and under current examination. Applicants' arguments and amendments filed 07/28/2023, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claim(s) 1, 5, 6, 8-9, 14, and 18-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frank et al. (Povidone-Iodine use in sinonasal and oral cavities: A review of safety in the COIVD-19 era) as evidenced by Kochelek (Misleading math: kill claims and log reduction).
Frank et al. teach providing 5% PVP-I (iodophor) in both nostrils twice daily for 5 days eradicated methicillin resistant staphylococcus aureus (MRSA) and reduced rate of methicillin-sensitive staphylococcus aureus (MSSA) by 94% in human patients who were positive for MSSA or MRSA, see Results section titled Sinonasal PVP-I Uses and Safety. Thus, Frank et al. anticipates a duration of at least 3 days and no longer than 15 days and administering no more than 6 times daily. Since the MRSA of patients who tested positive in the nostrils was eradicated this meets the limitation of reducing a first bacterial load of MRSA to a second bacterial load of zero as MRSA infection is prevented. The MRSA and MSSA of Frank et al. is prior to orthopedic surgery and since there is no discussion of a viral infection or pneumonia in these patients, the MRSA infection which is prevented is not viral or bacterial pneumonia but rather a surgical site infection including sepsis, see Results section titled Sinonasal PVP-I Uses and Safety. Since the MRSA is eradiated (i.e. complete kill) in the nose it would necessarily follow that the migration of bacteria is reduced in lung or anywhere since it is entirely eradicated. As evidenced by Kochelek, eradicated MRS reduces bacteria by at least 6 log/ml CF because a greater than or equal to 6 log reduction is reducing bacteria by 99.99%.
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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.
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) 1, 3-8, 10-14, 18-19 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al. (United States Patent Publication 20180207122-see IDS filed 1/10/2024) in view of Frank et al. (Povidone-Iodine use in sinonasal and oral cavities: A review of safety in the COIVD-19 era) and Infection control (3M launches Skin and Nasal Antiseptic for Preoperative Use- see IDS filed 1/10/2024) as evidenced by evidenced by Kochelek (Misleading math: kill claims and log reduction).
Scholz et al. teach disinfecting nasal tissue by applying an antiseptic composition comprising iodine or iodophor or a combination thereof, see claim 19. Subjects include humans, see paragraph [0080] and [0484]. The iodine or iodophor provides available iodine of preferably at least 0.25%, with see paragraph [0168] and claim 19. Scholz et al. teach that the antiseptic incudes polyvinylpyrrolidone iodine iodophor (PVP-I) which can be present at greater than 1% by weight, see paragraphs [0166]-[0167]. The composition remains at the site of application for at least 4 hours or 8 hours, see paragraph [0120]. The composition can be applied multiple times over one or more days, see paragraph [00117] and [0378]. The application can be made once or 2-4 times, see paragraph [0378]. Film forming polymers can be used to retain the active antimicrobial component at the afflicted site for longer period of time, see paragraph [0328]. The antimicrobial composition achieves at least a 4 log reduction in bacteria, see paragraph [0051] and can decolonize nasal cavities, or the oral cavity, see paragraph [0111]. Since the antiseptic composition decolonizes and provides a log reduction of bacteria, this meets reducing a first bacterial load to a second bacterial load which is lower. As the composition of Scholz can prevent microbes such as bacteria, it can prevent infection of internal cavities, see paragraph [0002],[0021] and [0088]. Since the bacterial infection can be prevented there would be no migration to external locations of the bacteria being treated. The method includes treating which improves clinical symptoms of a condition or decolonization which does not cause immediate clinical symptom. Since the composition treats conditions to improve clinical symptoms, the bacteria is suggested in Scholz to impart symptoms and be treated. The composition treats otitis media or sinusitis, see paragraph [0356]. Otitis media is not a bacterial pneumonia or post bacterial pneumonia infection. The method prevents infections caused by microorganisms including e. coli and Streptococcus pneumoniae, Escherichia and Staphylococcus aureus, see paragraphs [0021],[0089] and [0092], [0108]-[0109]. Since the treatment prevents microorganisms, pneumonia and bacteremia are necessarily prevented. The infection includes colonization of Staphylococcus aureus in the nares and thus is not a post viral or bacterial pneumonia infection. The application of the antiseptic composition occurs before an infection as Scholz teaches prevention of infections. The antiseptic can be delivered to an already infected or at risk nasal tissue, see paragraph [0376] thus can also occur after infection of microbes. The bacteria being treated include Streptococcus spp, and Staphylococcus aureus see paragraphs [0057] and [0071]. A hydroxycarboxylic acid can be included at least 1% by weight and include up to 99% by weight which meets the at least 2.5% in instant claim 22. The thickener can be present at 0.5% by weight which meets the at least 0.25% in instant claim 22, see paragraph [0319]. Surfactants can be present in at least 0.1% by weight rendering obvious instant claim 22 to at least 0.1% by weight see paragraph [0252]. Scholz et al. teach that the antiseptic provides at least a 4 log reduction of initial inoculum of 1-3x 107 CFU/mL or at least 6 log against microorganisms after a 5 min exposure time, see paragraphs [0071] and [0115] and claim 24. Scholz et al. teach that the microorganisms being treated include Psuedomonas aeruginosa or methicillin resistant Staphylococcus aureus, see paragraph [0092]. Scholz teaches that their composition provides complete prevention or elimination of bacteria to prevent time to infection of internal cavities such as the lung, see paragraph [0088]. The composition provides at least a 4 log 10 reduction of bacteria, however prevention of bacteria infection would provide at least a 6 log reduction because as evidenced by Kochelek, a greater than or equal to 6 log reduction is reducing bacteria by 99.99%. Therefore, prevention or eradication of the bacteria would at least be a 6 log reduction of bacteria.
Scholz suggests administering 2-4 times over one or more days. Scholz does not teach at least 3 days up to 15 days and applying the antiseptic composition before the first bacterial load is present or up to 25 hours before bacterial load is present.
Frank et al. teach placing PVP-I in both nostrils twice daily for 5 days completely eradicates MRSA and reduces rate of infection by 94%, see Sinonasal PVP-I uses and safety under results. In another study, PVP-I solution is administered 12 hours prior to surgery decreased the number of patients that get colonized with MRSA 4 hours after treatment, see results. A randomized trial provide PVP-I 2 hours prior to surgery and noted significant decrease in the number of patients with MRSA 4 hours after treatment.
According to Infection Control, nasal antiseptic is designed to be applied before surgery to reduce S. aureus colonization in the nares post-surgery. The antiseptic is PVP-I. Staphylococcus aureus is the leading cause of surgical site infections with approximately 80 percent of S. aureus infections caused by the patient’s own nasal flora. The nasal antiseptic helps to reduce risk of infection including MRSA, see pages 1-3.
It would have therefore been prima facie obvious before the effective filing date of the claimed invention to administer the PVP-I of Scholz et al. at least 12 hours before surgery which is before infection can occur because such administration of PVP-I acts to prevent the colonization of MRSA during surgery as Frank et al. teach complete eradication of MRSA. Since 80 percent of S. aureus infections are the result of the patient’s’ nasal flora one of ordinary skill in the art would have been motivated to administer the PVP-I of Scholz at least 12 hours before surgery to reduce colonization of S. aureus. It would have additionally been prima face obvious to one of ordinary skill in the art to administer the PVP-I of Scholz at an interval of twice daily for five days to completely eradicate MRSA from the nostrils of patients because PVP-I is taught by Frank et al. to be administered twice daily for 5 days to eradicate MRSA.
Claim(s) 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al. (United States Patent Publication 20180207122-see IDS filed 1/10/2024) in view of Frank et al. (Povidone-Iodine use in sinonasal and oral cavities: A review of safety in the COIVD-19 era) and Infection control (3M Launches Skin and Nasal Antiseptic for Preoperative Use-see IDS filed 1/10/2024) as evidenced by Kochelek (Misleading math: kill claims and log reduction) as applied to all claims above, and further in view of Goodall et al. (United States Patent Publication 20200316109).
The teachings of Scholz et al., Frank et al. and Infection Control are discussed above. Neither Scholz et al., Frank et al. nor Infection Control expressly teach that the antiseptic is applied to the nose and/or mouth a least 4 hours after a first bacterial load or at least 24 hours after.
Goodall et al. teach administering PVP-I can be intranasally administered 24 hours after first symptoms of a cold appear, see paragraph [0054]-[0056]. PVP-I is known to eradicate antibiotic resistant bacteria from nasal passages, see paragraph p[0089]. The treatment alleviates illnesses such as otitis media or sinusitis , see paragraphs [0028] and [0050]. Treatment encompasses 4 times a day spray for no longer than 5 days, see paragraphs [0133]-[0134].
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide the intranasal treatment of PVP-I taught in Scholz et al. after a least 24 hours when exhibiting symptoms. One of ordinary skill in the art would have been motivated to do so because Goodall et al. teach that PVP-I can be intranasally administered 24 hours after illness including cold and that PVP-I is useful in eradicating anti-biotic resistant bacteria from the nasal passages.
There would have been a reasonable expectation of success because both Scholz and Goodall teach administering PVP-I to the nasal passage.
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al. (United States Patent Publication 20180207122-see IDS filed 1/10/2024) in view of Frank et al. (Povidone-Iodine use in sinonasal and oral cavities: A review of safety in the COIVD-19 era) and Infection Control Today (3M Launches Skin and Nasal Antiseptic for Preoperative Use-see IDS filed 1/10/2024) and Kochelek (Misleading math: kill claims and log reduction) as applied to claims 1, 3-8, 10-14, 18-19 and 22 above, and further in view of Hoekstra et al. (Povidone-iodine ointment demonstrates in vitro efficacy against biofilm formation).
The teachings of the modified Scholz et al. are discussed above.
Neither Scholz et al., Frank et al. nor Infection Control today teach a bacterial load of at least 10,000 CFU per milliliter (cfu/mL) with a second bacterial load of no greater than 100 CFU per milliliter. This is interpreted as a reduction in bacterial load after administration of the antiseptic from over 10,000 cfu/mL to no greater than 100cfu/mL.
However, Hoekstra et al. teach PVP-I inoculated with P. aeruginosa and MRSA with an initial concentration of 5x107, see preparation of inoculum and biofilm formation section under methods. Treatment with PVP-I showed a greater than 5 log reduction against MRSA, see Candida albicans/MRSA biofilms section on page 3. PVP-I displayed a greater than 6 log reduction against Pseudomonas aeruginosa, see page 3 results at Pseudomonas aeruginosa biofilms section. A 6 log reduction is 5x107/106 which is equivalent to 50 cfu (5x101).
Thus, it would have been prima facie obvious to utilize the PVP-I of Scholz et al. to achieve a greater than 6 log reduction against bacteria including Pseudomonas aeruginosa because Hoekstra teaches the superior biocidal activity of PVP-I in which there is a starting inoculum of 5x107 wherein there can be a log6 reduction in Pseudomonas aeruginosa resulting in 50 cfu.
There would have been a reasonable expectation of success because Scholz et al. teach at least 6 log against microorganisms after a 5 min exposure time, see paragraphs [0071] and [0115] and that the microorganism being treated include Psuedomonas aeruginosa or MRSA (methicillin resistant Staphylococcus aureus, see paragraph [0092].
Response to Remarks
Applicants argue that Frank does not teach in vivo therapeutic results such that a bacterial load is reduced by at least 2 log CFU/ml relative to saline. Applicants argue that Frank does not disclose any migration of bacteria. The present invention shows that nasals passages treated with Nasla Prep 25 hours prior to infection had fewer than 1% of the bacteria than that of a saline group thus showing a marked reduction in migration.
Applicants arguments are considered unpersuasive because Frank teaches the complete eradication of MRSA after administration to the nasal passageway which is the same administration method as claimed. A complete eradiation of bacteria would as evidenced by Kochelek result in at least a log 6 reduction of bacteria. The prior art teaches administering the composition via the same route the nasal passageway. [T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
Applicants argue that Scholz does not teach a reduction of bacteria in the lung or blood by at least 2 log CFU/ml. Applicants argue that a prevention of bacteria does not establish a prima facie reason of obviousness because a reduction in bacteria does not provide the reduction in migration to the reduced downstream locations of at leat 2 log CFU/mL. Applicants point to the specification showing that the 25 hours prior to administration provided a 2.69 log reduction whereas the 6 hours prior and 35 hours post groups did not uniformly track towards stronger protection.
Applicants arguments are considered unpersuasive because the examiner takes the position if bacteria after administration via the same route to the nasal passage way is eradicated or completely prevented there is no migration of bacteria as there is a complete kill of bacteria. Furthermore, Scholz et al. specifically teaches prevention of infections. The composition of Scholz provides at least a 4 log 10 reduction of bacteria, however prevention of bacterial infection would provide at least a 6 log reduction because as evidenced by Kochelek, a greater than or equal to 6 log reduction is reducing bacteria by 99.99%. Therefore, prevention or eradication of the bacteria would at least be a 6 log reduction of bacteria because prevention of infections means that the bacteria does not have the chance to travel as it is eradicated. Frank et al. teach placing PVP-I in both nostrils twice daily for 5 days completely eradicates MRSA. If the bacteria is completely eradicated after administration to the nose then it would not be given the chance to travel to secondary sites or become septic. Accordingly, Applicants remarks are considered unpersuasive.
Conclusion
Currently, no claims are allowed and all claims are rejected. b
Applicant’s arguments/remarks are considered unpersuasive and the amendments to the claims necessitated new grounds of rejections. 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 extension fee 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH ALAWADI whose telephone number is (571)270-7678. The examiner can normally be reached Monday-Friday 10:00am-6:30pm EST.
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/SARAH ALAWADI/Primary Examiner, Art Unit 1619
