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 .
Status of the Claims
Claim 4 was cancelled in a previous communication. Claims 2 and 8 have been cancelled. Claims 1, 3, 5-7 and 9-11 are pending. Claims 9-11 have been withdrawn.
Claims 1, 3 and 5-7 are currently under examination.
All rejections not reiterated have been withdrawn.
Information Disclosure Statement
Initialed and dated copies of Applicants’ information disclosure statements (IDS)
filed on 10/09/2025 and 01/08/2026 are attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure
statement has been considered by the examiner.
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 1-3, 5, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Dees et al. (US8974363B2, Published 03/10/2015; cited in the IDS filed 03/24/23).
The claims are examined in view of the elected species rose Bengal disodium and Staphylococcus aureus.
Applicant’s Invention
The applicant’s claims are drawn to a method of treating a Gram-positive bacteria that are drug-susceptible and/or drug-resistant that comprises the steps of: a) contacting said Gram-positive bacteria with an aqueous pharmaceutical composition containing a rose Bengal disodium (RB) dissolved or dispersed therein at a concentration of about 0.2 to about 3.1 μg/mL; and b) irradiating those contacted bacteria with light of the wavelength about 500 nm to about 600 nm for a time period of about 1 to about 10 minutes to provide a light dose of about 1.4 to about 3.6 J/cm2.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1 and 7, Dees teaches a preferred embodiment of this method of treatment or medical use, applicants have found that application of an aqueous solution containing Rose Bengal at a concentration of approximately 1 to 10 micromolar or greater to antibiotic resistant (i.e., drug resistant) Staphylococcus aureus (i.e., gram-positive bacteria), various other gram-positive bacteria (column 13, lines 30-36). Dees also teaches wherein said halogenated xanthene comprises disodium Rose Bengal (claim 1, column 18, line 66-67). Dees further teaches by illumination of continuous or pulsed green light in the 500-600 band (i.e., wavelength) (column 13, lines 39-40). Dees also teaches activation may occur, following application of the medicament to tissue, upon exposure of such tissue to light at intensities of 10 mW/cm2 or less and at doses of 10 J/cm2 or less (column 9, lines 55-61).
Regarding claim 3, Dees teaches the method of application of an aqueous solution containing Rose Bengal at a concentration of approximately 1 to 10 micromolar or greater to antibiotic resistant Staphylococcus aureus (i.e., gram-positive bacteria) (column 13, lines 30-36).
Regarding claim 5, Dees teaches that the medicaments disclosed herein are broadly applicable to improved treatment of various conditions related to microbial or parasitic infection of humans or animals (i.e., mammalian), wherein the medicament can be applied directly to, or substantially proximal to, tissues to be treated (column 13, lines 12-17). The term “ microbial infection” refers to the presence of bacteria on a tissue and therefore cell of humans or animals (mammalian).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Dees does not specifically teach a concentration of about 0.2 to about 3.1µg/mL and irradiating the bacteria for a time period of about 1 to about 10 minutes to provide a light dose of about 1.4 to about 3.6 J/cm2. Dees also does specifically teach irradiating the bacteria for a time period of about 2 to about 5 minutes to provide a light dose of about 1.4 to about 3.6 J/cm2.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-143)
The claims are considered prima facie obvious to one of ordinary skill in the art at the time of filing because Dees teaches the claimed elements. It would have been prima facie obvious at the time of filing to contact staphylococcus aureus with an aqueous composition containing Rose Bengal disodium and irradiating the bacteria with light because it leads to substantial or complete eradication of such microbes, with little or no side effects in surrounding tissues (column 13, lines 40-42). With regards to the concentration of about 0.2 to about 3.1 µg/mL, Dees teaches an aqueous solution containing Rose Bengal at a concentration of approximately 1 to 10 micromolar or greater. The range of the prior art overlaps with the range of instant claim 1. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05 (I).
With regards to irradiating the bacteria for a time period of 1 to about 10 minutes and 2 to about 5 minutes, to provide a light dose of about 0.7 to about 7.2 J/cm2 and 1.4 to about 3.6 J/cm2 as required by instant claims 1 and 7, Dees teaches intensities of 10 mW/cm2 or less and at doses of 10 J/cm2 or less. So it would have been a matter of routine for one of ordinary skill in the art at the time of filing to calculate the number of minutes required for any given wattage of the light source. The ranges in the prior art that one would arrive at using approximately the intensities of 10 mW/cm2 or less and at doses of 10 J/cm2 or less would implicitly lead you to the amount of time of the instant claims. One milliwatt is equal to 0.6 joules/minute, so it would have been matter of routine for one of ordinary skill in the art to calculate the minutes with the information from the prior art and the ranges are implicitly taught in the prior art.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Dees et al. (US8974363B2, Published 03/10/2015; cited in the IDS filed 03/24/23) as applied to claims 1, 3, 5, and 7 above in view of Perez-Laguna et al (Photodiagnosis and Photodynamic Therapy, Published March 2018, Volume 21, Pages 211-216; cited in the IDS filed 03/24/23).
Applicant’s Invention
Dees render obvious all the limitations of instant claim 1. Applicant’s claim 6 further adds the limitation wherein said gram-positive bacteria are present as a biofilm.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding 6, Dees teaches the method of application of an aqueous solution containing Rose Bengal at a concentration of approximately 1 to 10 micromolar or greater to antibiotic resistant Staphylococcus aureus (i.e., gram-positive bacteria) (column 13, lines 30-36).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Dees does not teach wherein the gram-positive bacteria are present as a biofilm.
In the analogous art of antimicrobial photodynamic activity, Perez-Laguna teaches antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy to antibiotics especially against superficial infections caused by bacteria involved in multidrug resistance processes (abstract). Perez-Laguna also teaches comparing the efficacy of aPDT using the photosensitizer Rose Bengal (RB), combined or uncombined with gentamicin (GN), against Staphylococcus aureus. Different concentrations of RB (ranging from 0.03 to 64 μg/ml) were added to S. aureus in water suspensions or forming biofilms in the absence or presence of GN (abstract). Perez-Laguna also teaches in biofilm state, the bacteria are attached to a substratum, interface, or to each other and are embedded in a matrix of extracellular polymeric substance which isolates and protects them. As a result, biofilm-associated infections lead to chronic diseases because the host immune response is largely ineffective and are difficult to treat with antibiotics (Introduction second paragraph).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to irradiate the gram-positive bacteria present as a biofilm in Dees’ method for photodynamic treatment of disease. Dees teaches contacting gram-positive bacteria containing a Rose Bengal disodium and then irradiating the contacted gram-positive bacteria with light. One having ordinary skill in the art would have understood in view of Perez-Laguna that biofilm-associated infections lead to chronic diseases because the host immune response is largely ineffective and are difficult to treat with antibiotics (Introduction second paragraph). It would have been prima facie obvious at the time of filing to irradiate gram-positive bacteria present as a biofilm in Dees’ method because Dees teaches the improved treatment of various conditions related to microbial or parasitic infection of humans or animals, wherein the medicament can be applied directly to, or substantially proximal to, tissues to be treated (column 13, lines 12-17), and Perez-Laguna teaches biofilm-associated infections lead to chronic diseases because the host immune response is largely ineffective and are difficult to treat with antibiotics (Introduction second paragraph). It would have been obvious because antimicrobial photodynamic therapy gives the advantage of eliminating microorganisms independently of their antimicrobial resistance pattern and is also effective against microorganisms in the biofilm state. Moreover, the advantages include the low probability of the occurrence of side effects and the convenient cost of treatment. The skilled artisan would have had a reasonable expectation of success because Perez-Laguna teaches a nearly identical compound which is effective against biofilms.
Response to Arguments
Applicant's arguments filed 04/22/2025 have been fully considered but they are not persuasive.
On pages 7-9 of Applicants remarks, Applicants argue that Dees states that the treatment of Staphylococcus aureus was done by illumination with approximately 10-200 J/cm2 in the 500-600 nm band. This is particularly intense light and is significantly greater and more intense than the light used in the claimed invention of about 1.4 to about 3.6 J/cm2. Therefore, one skilled in the art would find no suggestion in Dees that treatment of Gram-positive bacteria that are drug-susceptible and/or drug-resistant with rose Bengal would be successful at the low illumination intensity of the claimed method. Applicants further argue that the claimed method is very effective in killing such Gram-positive bacteria. This highly successful result in a low intensity light dose is unexpected over prior disclosures which required significantly more intense light. The result is a much better and advantageous method of treatment. Applicants also argue that there is no support in Dees that less than 10 J/cm2 can be used as the “or less” for this light intensity is only mentioned once in Dees.
These arguments are not persuasive. The examiner points out that in the first section in column 9, Dees teaches the individual dose of the light at 10 J/cm2 or less, whiles the section in column 13, 10 to 200 J/cm2, is referring to the total administration of the doses in entirety, therefore, 10 J/cm2 or less taught in column 9 is referring to an individual dose, whereas 10 to 200 J/cm2 taught in column 13 is referring to the total administration amount which can encompass multiple doses to achieve up to 200 J/cm2 for total administration. Therefore, the two sections are connected, clear, and not contradictory sections. The examiner further point out that that in the second section, column 13, after teaching the use of 10 to 200 J/cm2, the next sentence states that “The present invention, however, is not limited to this preferred embodiment, as other medicaments disclosed herein can also be used.” Therefore, applicants are relying on a preferred embodiment wherein Dees also teaches in the first section in column 9 that the individual dose of the light can be at 10 J/cm2 or less.
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed."). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." Id. at 554, 31 USPQ2d at 1132.). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Insomuch as this may be an assertion of unexpected results, please refer to MPEP 716.02(b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims. The examiner points out that applicant not has met the burden to show how their instantly claimed ranges are tied to any allegedly unexpected property. Therefore the claims are considered prima facie obvious for the reasons set forth in the rejection. Applicant’s comments about Dees’ recitation of “or less” is of no real help are noted. The examiner disagrees because 10 mW/cm2 or less and at doses of 10 J/cm2 or less can only be interpreted to mean anything less than 10 mW/cm2 and 10 J/cm2, which includes applicant’s claimed range of the light dose. Please see above regarding the burden on Applicant to establish that a claimed range is critical to an unexpectedly superior property.
On page 9 of Applicants remarks, Applicants argue that Parez-Laguna et al. disclosures do not overcome the deficiencies of Dees towards the present claims.
The Examiner points out that Parez-Laguna was only relied on for the rejection of claim 6 for the teaching of the gram-positive bacteria being present as a biofilm and not for the irradiation doses which were already taught in Dees.
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 1, 3, 5, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. US8974363B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the application claims render obvious the instant claims.
Inter alia the ‘363 patent embraces a medicament consisting of a hydrophilic vehicle containing a halogenated xanthene wherein said halogenated xanthene comprises disodium rose Bengal. The invention of the ‘363 patent is considered to embrace a method of treatment or medical use, applicants have found that application of an aqueous solution containing Rose Bengal at a concentration of approximately 1 to 10 micromolar or greater to antibiotic resistant (i.e., drug resistant) Staphylococcus aureus (i.e., gram-positive bacteria), various other gram-positive bacteria (column 13, lines 30-36). The ‘363 specification further teaches by illumination of continuous or pulsed green light in the 500-600 band (i.e., wavelength) (column 13, lines 39-40). The ‘363 patent also embraces the method of improved treatment of various conditions related to microbial or parasitic infection of humans or animals, wherein the medicament can be applied directly to, or Substantially proximal to, tissues to be treated (column 13, lines 12-17).
With regards to the concentration of the instant claims, the ‘363 patent embraces the same compound, so it would be obvious to optimize the amount of concentration to achieve the desired effects of killing the gram-positive bacteria. With regards to the time period of irradiating those contacted bacteria, the ‘363 patent embraces the method of irradiating the bacteria with intensities of 10 mW/cm2 or less and at doses of 10 J/cm2 or less (column 9, lines 55-61). One milliwatt is equal to 0.6 joules/minute, so it would have been a matter of routine for one of ordinary skill in the art to calculate the minutes with the information from the ‘363 patent and the ranges are implicitly taught in the ‘363 patent.
The examiner has relied upon the specification to delineate the scope of the invention embraced by the US8974363B2 application/patent, consistent with the decision in Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co. U.S. Court of Appeals Federal Circuit, 95 USPQ2d 1797.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. US8974363B2 as applied to claims 1-3, 5, and 7 above in view of Perez-Laguna et al (Photodiagnosis and Photodynamic Therapy, Published March 2018, Volume 21, Pages 211-216; cited in the IDS filed 03/24/23).
The relevant limitations of the ‘363 patent are set forth above.
The ‘363 patent does not teach wherein said gram-positive bacteria are present as a biofilm. However Perez-Laguna teaches antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy to antibiotics especially against superficial infections caused by bacteria involved in multidrug resistance processes (abstract). Perez-Laguna also teaches in biofilm state the bacteria are attached to a substratum, interface, or to each other and are embedded in a matrix of extracellular polymeric substance which isolates and protects them. As a result, biofilm-associated infections lead to chronic diseases because the host immune response is largely ineffective and are difficult to treat with antibiotics (Introduction second paragraph). It would have been obvious to irradicate the gram-positive bacteria which is present as a biofilm because antimicrobial photodynamic therapy gives the advantage of eliminating microorganisms independently of their antimicrobial resistance pattern and is also effective against microorganisms in the biofilm state. Moreover, the advantages include the low probability of the occurrence of side effects and the convenient cost of treatment.
Response to Arguments
Applicant's arguments filed 01/30/2026 with respect to the nonstatutory double patenting rejection have been fully considered but they are not persuasive.
On page 9 of Applicants remarks, Applicants argue that the claims of the present application do not recite the same features as Dees. Further, as explained above, the claims of the present application are patentably distinct over Dees.
Applicants argument have been noted. The rejection is maintained in the absence of a terminal disclaimer for the reasons set forth in the rejection and the reasons in the response to arguments set forth above.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617 /ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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