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 1-20 are pending.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 3/2/2026 has been entered.
Response to Preliminary Amendment and Arguments
1. Applicant Arguments, filed 3/2/2026, at p. 7, 2d paragraph, appears to traverse the Patent Board Decision, mailed 12/30/2025, (hereinafter “Decision”), regarding the claim 1 limitation “to cause extracellular matrix crosslinking throughout the wound.” which states
The Decision at p. 12, 2d paragraph, states: “Appellant argues that, because the chromophore in Loupis' method is not used ‘to cause extracellular matrix crosslinking through the wound’ as recited in claim 1, Loupis' method does not require direct contact between the chromophore and the surface of the wound. Id. [Appel Br.7] at 8-9.
The Board, then states:
We are not persuaded for the reasons discussed above. That is, Loupis teaches that photodynamic therapy for wound healing, which requires direct application of a photosensitive agent (e.g, a chromophore) to the target skin, is known in the art. Loupis 23:3-5. Loupis further teaches that use of chromophores as a catalyst for photo-polymerization is also known. Id. at 36:23-24. Thus, Loupis renders the method of claim 1 obvious without rendering its own method unsatisfactory for its intended purpose. See, e.g., In re Fulton, 391 F.3d at 1200 (explaining that the question for obviousness is "whether there is something in the prior art as a whole to suggest the desirability, and thus the obviousness, of making [claimed] combination, not whether there is something in the prior art as a whole to suggest that the combination is the most desirable combination available") (internal quotation marks and citation omitted).
Decision at p. 12.
Thus the Applicant Arguments continue to urge, in prosecution, a claim limitation that was fully considered by Board of Appeals in the Decision, and has not been further amended.
Claim Interpretation
Newly amended claim 1 contains the limitation “immediately after application, illuminating the wound . . . .” There is no limiting definition of “immediately” in the instant Specification and no duration of time specified for “immediately.” Therefore, the claim term, as defined in the dictionary is used to interpret the claim limitation:
PNG
media_image1.png
373
671
media_image1.png
Greyscale
IMMEDIATELY Definition & Meaning - Merriam-Webster, accessed 15 Mar 2026.
Claim Rejections - 35 USC § 112
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 1 and its dependent claims 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.
The term “immediately” in claim 1 is a relative term which renders the claim indefinite. The term “immediately” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Reply, filed 3/2/2026, at p. 6, paragraph, 2, argues that photodynamic therapy requires a wait time of 1-72 hours to allow internalization of photosensitizer into cells, thereby distinguishing the claims from the teachings of Loupis. Thus, in consideration of the Reply, the term “immediately” can be taken to have a numerical time component. However, there is no limiting definition of “immediately” in the instant Specification and no duration of time specified for “immediately.”
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.
1. Claim(s) 1-16 and 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loupis et al., 2015 (WO 2015/000058 A1), of record.
Loupis at para [0243], states that the first or second chromophore can be activated by ambient light which may originate from the sun or other light sources or without a visible source, which suggests immediate illumination. Loupis at [0299] states that a layer of biophotonic composition was topically applied to a wound of a patient and illuminated for 5 minutes with a blue LED light, which suggests straightway application of light without a meaningful interval of time.
Claims 1-16 and 18-19 are directed to a method for improving secondary intention healing of an epithelial tissue wound, the method comprises delivering an activating agent to a surface of the wound by painting, brushing, spraying, dripping or injecting, wherein the wound is an open wound without its edges brought together, irradiating the wound with an electromagnetic radiation source, and activating the activating agent to cause extracellular matrix crosslinking throughout the wound. Claim 2 specifies the step of delivering includes topically applying the activating agent to the surface of the wound. Claim 3 specifies the step of applying includes using an applicator to apply the activating agent to the wound, and the application is one of sponge, a brush, a cotton tip, and a needle. Claims 4-5 specify the step of irradiating is performed for a duration between about one minute to about thirty minutes and less than about five minutes, respectively. Claims 6-7 specify the step of irradiating is performed using the electromagnetic radiation source having a wavelength between about 350 nm to about 800 nm and between about 400 nm to about 700 nm, respectively. Claim 8 specifies the activating agent is Rose Bengal (elected species). Claim 9 specifies the step of irradiating includes using one of a laser, a lamp, a light-emitting diode, and a light-emitting diode array. Claim 10 specifies the wound contains a tissue graft. Claims 11 specifies the wound is a full thickness skin wound. Claim 12 specifies the wound is a partial thickness skin wound. Claim 13 specifies the step of irradiating is performed at an irradiance of less than about one W/cm2. Claim 14 further comprises repeating the steps of delivering, irradiating and activating periodically until the wound is closed. Claim 15 further comprises repeating the steps of delivering, irradiating and activating periodically until the wound is fully healed. Claim 16 further comprises applying a tissue graft to the wound after the step of delivering, irradiating and activating. Claim 18 further comprises selecting one from a group consisting of cells and growth factors, and applying the selection to the wound after the steps of delivering, irradiating and activating. Claim 19 specifies the cells include epithelial cells.
Regarding claims 1-2 and 8, Loupis teaches Non-healing wounds means wounds that do not heal in an orderly set of stages and a predictable amount of time and rate in the way that most normally-healing wounds heal, and non-healing wounds include incompletely healed wounds, delayed healing wounds, impaired wounds, difficult to heal wounds and chronic wounds. A non-healing wound may include 1) a prolonged inflammatory phase, 2) a slow forming extracellular matrix, and/or 3) a decreased rate of epithelialization or closure (e,g, p. 26, lines 13-21). A biophotonic composition comprising at least a first chromophore and a gelling agent to render the biophotonic composition resistant to leaching. The first chromophore is a fluorescent chromophore, such as Xanthene dye or Rose Bengal (e.g. claims 1, 37-39). Loupis teaches a method for promoting and/or stimulating repair, or increasing the rate of repair, in non-healing wounds, comprising applying topically a biophotonic composition to a non-healing wound, and illuminating said biophotonic composition with light having a wavelength that overlaps with an absorption spectrum of the first chromophore (e.g. claims 96-97). A method for stimulating and/or promoting repair at the center and/or edge of a non- healing wound, comprising applying topically a biophotonic composition to a non- healing wound, and illuminating said biophotonic composition with light having a wavelength that overlaps with an absorption spectrum of the first chromophore (e.g. claim 98). The stimulated repair is delayed at the edge compared to the center (e.g. claim 99), or the stimulated repair is increased at the center compared to the edge (e.g. claim 100).
Regarding claim 3, Loupis teaches the biophotonic composition may be applied to or impregnated into a material such as a pad, dressing, a woven or non-woven fabric. The composition can be applied to a substrate, such as a sponge (e.g. p. 10, lines 10-18). Regarding claims 4-5, Loupis teaches the biophotonic composition is illuminated for any time period per treatment in which the biophotonic composition is activated, for example, about 1 minute to about 30 minutes, preferably less than about 5 minutes (e.g. p. 14, lines 9-15).
Regarding claims 6-7, Loupis teaches the first chromophore absorbs or emits light at a wavelength of 200-600 nm, 400-800 nm, or 400-600 nm (e.g. p. 8, lines 6-15).
Regarding claim 9, Loupis teaches the "actinic light" or "light" is intended to mean light energy emitted from a specific light source (e.g. lamp, LED, or laser) (e.g. p. 25, lines 19-22).
Regarding claims 10, 12 and 18-19, Loupis teaches prior to undergoing the biophotonic treatment, the patient underwent multiple surgical procedure and wound healing treatment including split thickness skin grafting (e.g. page 76, line 28, to page 77, line 3). The split thickness skin grafting is a tissue graft and it is in contrast to a full thickness skin graft. Therefore, the wound is a partial thickness skin wound. Further, the split thickness skin graft would contain cells, such as epithelial cells.
Regarding claim 11, Loupis teaches the biophotonic compositions and methods for treating and/or promoting healing Grade I-IV ulcers. The Grade IV wound is full- thickness wounds (e.g. page 57, lines 11-18).
Regarding claim 13, Loupis teaches the biophotonic composition is illuminated with light having a power density of less than about 150 mW/Cm2, which is less than one W/cm2.
Regarding claim 14-15, Loupis teaches the method for biophotonic treatment of non-healing wounds can be applied in or on the wound daily, or once, twice, three times, four times, five times or six times a week, or at any other frequency (e.g. p. 15, lines 21- 23). Regarding claim 16, Loupis teaches all wounds responded to the biophotonic method and composition by progressing to granulation, and as of the end of the case study period, 8 wounds were completely closed without surgical intervention. Two additional patients progressed to wound closure through surgery (skin graft) (e.g. p. 76, lines 12-19).
Regarding claim 18, Loupis teaches additional components may be included or used in combination with the biophotonic compositions. Such additional components include growth factors, which may be applied to the wound, skin or mucosa in a topical fashion (e.g. p. 45, line 25 to page 46, line 4).
Loupis teaches a kit comprising a first composition comprising the oxygen releasing agent and a second composition comprising a first chromophore in the gelling agent (e.g., p. 61, lines 21-23). The kit includes a first container comprising a first composition comprising the oxygen-releasing agent, and a second container comprising a second composition comprising at least one chromophore. Exemplary containers include syringes, vials or pouches. The first and second compositions may be included within the same container and the container may be a dual-chamber syringe where the contents of the chambers mix on expulsion of the compositions from the chambers (e.g., p. 62, lines 20-28).
Loupis does not specifically teach delivering an activating agent to the surface of the wound by painting, brushing, spraying, dripping or injecting.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to deliver an activating agent to the surface of the wound by injecting because Loupis teaches a kit comprising a first container comprising a first composition comprising the oxygen-releasing agent, and a second container comprising a second composition comprising at least one chromophore. The first and second compositions may be included within the same container and the container may be a dual-chamber syringe where the contents of the chambers mix on expulsion of the compositions from the chambers. It was well known in the art that a syringe is used to inject the content in the syringe onto target site. Since the first and second compositions are in the same syringe, it would be obvious to one of ordinary skill in the art that the mixed compositions in the syringe would be injected and delivered to the surface of the wound and there is reasonable expectation of success to do so. One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to promote and/or stimulate repair, or increase the rate of repair, in non-healing wounds or to stimulate and/or promote repair at the center and/or edge of a non-healing wound as taught by Loupis with reasonable expectation of success.
2. Claim(s) 1-16 and 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loupis et al., 2015 (WO 2015/000058 A1), of record, in view of Kislev, Hanoch, 2008 (WO 2008/065652 A2), of record.
Loupis at para [0243], states that the first or second chromophore can be activated by ambient light which may originate from the sun or other light sources or without a visible source, which suggests immediate illumination. Loupis at [0299] states that a layer of biophotonic composition was topically applied to a wound of a patient and illuminated for 5 minutes with a blue LED light, which suggests straightway application of light without a meaningful interval of time.
Claims 1-16 and 18-19 are directed to a method for improving secondary intention healing of an epithelial tissue wound, the method comprises delivering an activating agent to a surface of the wound by painting, brushing, spraying, dripping or injecting, wherein the wound is an open wound without its edges brought together, irradiating the wound with an electromagnetic radiation source, and activating the activating agent to cause extracellular matrix crosslinking throughout the wound. Claim 2 specifies the step of delivering includes topically applying the activating agent to the surface of the wound. Claim 3 specifies the step of applying includes using an applicator to apply the activating agent to the wound, and the application is one of sponge, a brush, a cotton tip, and a needle. Claims 4-5 specify the step of irradiating is performed for a duration between about one minute to about thirty minutes and less than about five minutes, respectively. Claims 6-7 specify the step of irradiating is performed using the electromagnetic radiation source having a wavelength between about 350 nm to about 800 nm and between about 400 nm to about 700 nm, respectively. Claim 8 specifies the activating agent is Rose Bengal (elected species). Claim 9 specifies the step of irradiating includes using one of a laser, a lamp, a light-emitting diode, and a light-emitting diode array. Claim 10 specifies the wound contains a tissue graft. Claims 11 specifies the wound is a full thickness skin wound. Claim 12 specifies the wound is a partial thickness skin wound. Claim 13 specifies the step of irradiating is performed at an irradiance of less than about one W/cm2. Claim 14 further comprises repeating the steps of delivering, irradiating and activating periodically until the wound is closed. Claim 15 further comprises repeating the steps of delivering, irradiating and activating periodically until the wound is fully healed. Claim 16 further comprises applying a tissue graft to the wound after the step of delivering, irradiating and activating. Claim 18 further comprises selecting one from a group consisting of cells and growth factors, and applying the selection to the wound after the steps of delivering, irradiating and activating. Claim 19 specifies the cells include epithelial cells.
Regarding claims 1-2 and 8, Loupis teaches Non-healing wounds means wounds that do not heal in an orderly set of stages and a predictable amount of time and rate in the way that most normally-healing wounds heal, and non-healing wounds include incompletely healed wounds, delayed healing wounds, impaired wounds, difficult to heal wounds and chronic wounds. A non-healing wound may include 1) a prolonged inflammatory phase, 2) a slow forming extracellular matrix, and/or 3) a decreased rate of epithelialization or closure (e,g, p. 26, lines 13-21). A biophotonic composition comprising at least a first chromophore and a gelling agent to render the biophotonic composition resistant to leaching. The first chromophore is a fluorescent chromophore, such as Xanthene dye or Rose Bengal (e.g. claims 1, 37-39). Loupis teaches a method for promoting and/or stimulating repair, or increasing the rate of repair, in non-healing wounds, comprising applying topically a biophotonic composition to a non-healing wound, and illuminating said biophotonic composition with light having a wavelength that overlaps with an absorption spectrum of the first chromophore (e.g. claims 96-97). A method for stimulating and/or promoting repair at the center and/or edge of a non- healing wound, comprising applying topically a biophotonic composition to a non- healing wound, and illuminating said biophotonic composition with light having a wavelength that overlaps with an absorption spectrum of the first chromophore (e.g. claim 98). The stimulated repair is delayed at the edge compared to the center (e.g. claim 99), or the stimulated repair is increased at the center compared to the edge (e.g. claim 100).
Regarding claim 3, Loupis teaches the biophotonic composition may be applied to or impregnated into a material such as a pad, dressing, a woven or non-woven fabric. The composition can be applied to a substrate, such as a sponge (e.g. p. 10, lines 10-18).
Regarding claims 4-5, Loupis teaches the biophotonic composition is illuminated for any time period per treatment in which the biophotonic composition is activated, for example, about 1 minute to about 30 minutes, preferably less than about 5 minutes (e.g. p. 14, lines 9-15).
Regarding claims 6-7, Loupis teaches the first chromophore absorbs or emits light at a wavelength of 200-600 nm, 400-800 nm, or 400-600 nm (e.g. p. 8, lines 6-15).
Regarding claim 9, Loupis teaches the "actinic light" or "light" is intended to mean light energy emitted from a specific light source (e.g. lamp, LED, or laser) (e.g. p. 25, lines 19-22).
Regarding claims 10, 12 and 18-19, Loupis teaches prior to undergoing the biophotonic treatment, the patient underwent multiple surgical procedure and wound healing treatment including split thickness skin grafting (e.g. page 76, line 28, to page 77, line 3). The split thickness skin grafting is a tissue graft and it is in contrast to a full- thickness skin graft. Therefore, the wound is a partial thickness skin wound. Further, the split thickness skin graft would contain cells, such as epithelial cells.
Regarding claim 11, Loupis teaches the biophotonic compositions and methods for treating and/or promoting healing Grade I-IV ulcers. The Grade IV wound is full- thickness wounds (e.g. page 57, lines 11-18).
Regarding claim 13, Loupis teaches the biophotonic composition is illuminated with light having a power density of less than about 150 mW/Cm2, which is less than one W/cm2.
Regarding claim 14-15, Loupis teaches the method for biophotonic treatment of non-healing wounds can be applied in or on the wound daily, or once, twice, three times, four times, five times or six times a week, or at any other frequency (e.g. p. 15, lines 21- 23).
Regarding claim 16, Loupis teaches all wounds responded to the biophotonic method and composition by progressing to granulation, and as of the end of the case study period, 8 wounds were completely closed without surgical intervention. Two additional patients progressed to wound closure through surgery (skin graft) (e.g. p. 76, lines 12-19).
Regarding claim 18, Loupis teaches additional components may be included or used in combination with the biophotonic compositions. Such additional components include growth factors, which may be applied to the wound, skin or mucosa in a topical fashion (e.g. p. 45, line 25 to page 46, line 4).
Loupis teaches a kit comprising a first composition comprising the oxygen releasing agent and a second composition comprising a first chromophore in the gelling agent (e.g., p. 61, lines 21-23). The kit includes a first container comprising a first composition comprising the oxygen-releasing agent, and a second container comprising a second composition comprising at least one chromophore. Exemplary containers include syringes, vials or pouches. The first and second compositions may be included within the same container and the container may be a dual-chamber syringe where the contents of the chambers mix on expulsion of the compositions from the chambers (e.g., p. 62, lines 20-28).
Loupis does not specifically teach delivering an activating agent to the surface of the wound by painting, brushing, spraying, dripping or injecting.
Kislev teaches electromagnetic radiation absorbing nanoparticles operable for generating excited species when exposed to electromagnetic radiation in the microwave range, and methods for treatments based on controlled generation of excited species (e.g., Abstract). A method for treating a wound, comprising administering an absorbing nanoparticle to the wound region, and applying microwave radiation to said nanoparticle to induce formation of ROS (reactive oxygen species), or further comprising applying ultrasound radiation to form microbubble (e.g., claims 48-49). The nanoparticles are released locally with a suitable catheter equipped with a shaft carrying an array of needles in its distal end. Sliding the needles injects the nanoparticles throughout the infarcted myocardium volume, and the nanoparticles diffuse through the damaged myocardium tissue interstitium using ultrasound enhanced diffusion (e.g., p. 42, line 33 to page 43, line 6).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to deliver an activating agent to the surface of the wound by injecting because Loupis teaches a method for promoting and/or stimulating repair, or increasing the rate of repair, in non-healing wounds, comprising applying topically a biophotonic composition to a non-healing wound, and illuminating said biophotonic composition with light having a wavelength that overlaps with an absorption spectrum of the first chromophore, and a dual-chamber syringe for the administration of the first and second composition within the syringe. Kislev teaches a method for treating a wound, comprising administering an electromagnetic radiation absorbing nanoparticle to the wound region, and applying microwave radiation to said nanoparticle to induce formation of ROS (reactive oxygen species), and the nanoparticles are released locally with a suitable catheter equipped with a shaft carrying an array of needles in its distal end to inject the nanoparticles throughout the infarcted myocardium volume. Both Loupis and Kislev teach treating a wound with an active agent and an electromagnetic radiation. Loupis teaches a dual-chamber syringe for the administration of the first and second composition within the syringe, and Kislev teaches the nanoparticles can be injected locally to the infarcted myocardium volume by using a catheter carrying an array of needles. It would be obvious for one of ordinary skill in the art to inject the compositions taught by Loupis with the catheter carrying an array of needles as taught by Kislev in order to optimize the administration efficiency of the compositions to the wound for treating the non-healing wounds with reasonable expectation of success.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to promote and/or stimulate repair, or increase the rate of repair, in non-healing wounds or to stimulate and/or promote repair at the center and/or edge of a non-healing wound as taught by Loupis with reasonable expectation of success.
3. Claim(s) 1, 16-17 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loupis et al., 2015 (WO 2015/000058 A1), of record, in view of Austen et al., 2015 (US 20150134049 A1, IDS), of record.
Claims 1, 16-17 and 20 are directed to a method for improving secondary intention healing of an epithelial tissue wound, the method comprises delivering an activating agent to a surface of the wound by painting, brushing, spraying, dripping or injecting, wherein the wound is an open wound without its edges brought together, irradiating the wound with an electromagnetic radiation source, and activating the activating agent to cause extracellular matrix crosslinking throughout the wound. Claim 16 further comprises applying a tissue graft to the wound after the step of delivering, irradiating and activating. Claim 17 further comprises delivering the activating agent to the tissue graft, and irradiating the tissue graft with the electromagnetic radiation source. Claim 20 further comprises treating the wound with one of stromal vascular fraction, platelet rich plasma, fibrin, platelet-derived growth factor, TFG-beta, fibroblast growth factor, and epidermal growth factor after the steps of delivering, irradiating and activating.
Loupis teaches "Non-healing wounds" means wounds that do not heal in an orderly set of stages and a predictable amount of time and rate in the way that most normally-healing wounds heal, and non-healing wounds include incompletely healed wounds, delayed healing wounds, impaired wounds, difficult to heal wounds and chronic wounds. A non-healing wound may include 1) a prolonged inflammatory phase, 2) a slow forming extracellular matrix, and/or 3) a decreased rate of epithelialization or closure (e,g, p. 26, lines 13-21). A biophotonic composition comprising at least a first chromophore and a gelling agent to render the biophotonic composition resistant to leaching. The first chromophore is a fluorescent chromophore, such as Xanthene dye or Rose Bengal (e.g. claims 1, 37-39). Loupis teaches a method for promoting and/or stimulating repair, or increasing the rate of repair, in non-healing wounds, comprising applying topically a biophotonic composition to a non-healing wound, and illuminating said biophotonic composition with light having a wavelength that overlaps with an absorption spectrum of the first chromophore (e.g. claims 96-97). A method for stimulating and/or promoting repair at the center and/or edge of a non-healing wound, comprising applying topically a biophotonic composition to a non-healing wound, and illuminating said biophotonic composition with light having a wavelength that overlaps with an absorption spectrum of the first chromophore (e.g. claim 98). The stimulated repair is delayed at the edge compared to the center (e.g. claim 99), or the stimulated repair is increased at the center compared to the edge (e.g. claim 100).
Loupis does not specifically teach delivering the activating agent to the tissue graft, and irradiating the tissue graft with the electromagnetic radiation source, or treating the wound with one of stromal vascular fraction, platelet rich plasma, fibrin, platelet- derived growth factor, TFG-beta, fibroblast growth factor, and epidermal growth factor after the steps of delivering, irradiating and activating.
Austin at para [004] teaches cross-linking to be a part of normal wound healing. Austen at para [0096], [0112] teaches a photoactive agent that interacts with tissue, including extracellular matrix alterations upon photoactivation.
Austen teaches a method of preparing a non-adhesive tissue surface within a human subject by exposing an intact, non-proliferative, internal tissue surface located proximal to an incision in a human subject to a tissue structure stabilizing agent (TSSA) to promote cross-linking of proteins within the surface of the tissue, thereby preparing a non-adhesive tissue surface within the human subject. The tissue surface is located within a tissue such as connective, epithelial and muscle tissues etc. (e.g. [0010], [0011], claims 1-3). The tissue surface comprises previously grafted tissue (e.g. claim 4) (For claim 10). The TSSA is applied topically to the tissue surface and the TSSA is a photoactive agent or a chemical cross-linking compound (e.g. [0012], [0013], claims 5 and 7) (For claims 1-2). The TSSA is a photoactive agent and the method further comprises the step of irradiating the tissue surface at an irradiance of less than about 1 W/cm2 and the photoactive agent is Rose Bengal (RB) (e.g. [0014], claims 8-9 and 11- 12) (For claims 8 and 13). The irradiance is provided for a period between about 1 minute and 30 minutes or for less than about 5 minutes (e.g. [0015], claims 13-14) (For claims 4-5). Photoactive agents can be brushed, dripped or sprayed onto, or injected into, tissue surface prior to the application of electromagnetic energy and the electromagnetic radiation can be at an appropriate wavelength, energy and duration to cause passivation of the tissue surface. The wavelength can be from about 350 nm to about 800 nm, preferably from about 400 nm to about 700 nm, and the energy can be less than about 1 W/cm2 (e.g. [0099]) (For claims 3, 6-7 and 13). Suitable sources of electromagnetic energy can include lasers, lamps, light emitting diodes or other sources of electromagnetic radiation (e.g. [0101]) (For claim 9). Specific clinical applications also include passivation of tissue grafts and/or surgical sites to prevent contracture, scar contracture, capsular contracture around implants (e.g. [0110]). The passivated tissue graft refers to a tissue graft treated with a TSSA. Grafts thus passivated may be implanted into a subject to prevent or reduce stenosis in the subject (e.g. [0078]). Passivation of tissue prior to therapeutic use can be conducted according to the methods described herein to prepare improved tissue for therapeutic use (e.g. [0117]). Rose Bengal can be brushed onto tissue surfaces of a tissue prior to the application of electromagnetic energy, followed by irradiation at a irradiance of less than 1 W/cm2. Rose Bengal can be topically applied to a tissue graft and irradiating the tissue at an irradiance of less than about 1 W/cm2 (e.g. [0118]) (For claims 16-17). Tissue graft is prepared for implantation in a subject and the tissue graft comprises a tissue selected from the group consisting of vein, artery, bone, skin, muscle and cardiac tissue (e.g. [0034]) (For claims 18-19). A rabbit model for capsular contraction was developed. One model received Fibrin Glue+RB+532 nm light. Fibrin is known to produce a fibrotic reaction in the model. The pockets treated with PTP prior to fibrin glue application had less infiltrates. These cells also appear contained under layers of presumably, cross- linked collagen (e.g. [0121]) (For claim 20). The skin graft and cardiac tissue would contain epithelial cells and smooth muscle cells, respectively (For claims 18-19).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to deliver the activating agent to the tissue graft, and irradiating the tissue graft with the electromagnetic radiation source because Austen teaches passivation of tissue graft with a TSSA such as Rose Bengal, and Rose Bengal can be topically applied to a tissue graft and irradiating the tissue at an irradiance of less than about 1 W/cm2, wherein the tissue graft is prepared for implantation in a subject. Both Loupis and Austen teach applying skin graft to the wound, and since Austen teaches Rose Bengal can be topically applied to a tissue graft and irradiating the tissue at an irradiance of less than about 1 W/cm2, wherein the tissue graft is prepared for implantation in a subject, it would be obvious for one of ordinary skill in the art to deliver the activating agent to the tissue graft taught by Loupis, and irradiating the tissue graft with the electromagnetic radiation source in order to optimize the healing effect and efficiency in non-healing wounds with reasonable expectation of success. Further, Austen teaches fibrin is known to produce a fibrotic reaction in the model and teaches treating rabbit model with Fibrin Glue+RB+532 nm light. It would be obvious for one of ordinary skill in the art to further treating the wound with fibrin in order to optimize the effect of wound-healing or to optimize the healing effect and efficiency in non-healing wounds with reasonable expectation of success.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to promote and/or stimulate repair, or increase the rate of repair, in non-healing wounds or to stimulate and/or promote repair at the center and/or edge of a non-healing wound as taught by Loupis with reasonable expectation of success.
4. Claim(s) 1, 16-17 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Loupis et al., 2015 (WO 2015/000058 A1), of record, in view of Kislev, Hanoch, 2008 (WO 2008/065652 A2), of record, as applied to claims 1-16 and 18-19 above, and further in view of Austen et al., 2015 (US 20150134049 A1, of record, IDS).
Claims 1, 16-17 and 20 are directed to a method for improving secondary intention healing of an epithelial tissue wound, the method comprises delivering an activating agent to a surface of the wound by painting, brushing, spraying, dripping or injecting, wherein the wound is an open wound without its edges brought together, irradiating the wound with an electromagnetic radiation source, and activating the activating agent to cause extracellular matrix crosslinking throughout the wound. Claim 16 further comprises applying a tissue graft to the wound after the step of delivering, irradiating and activating. Claim 17 further comprises delivering the activating agent to the tissue graft, and irradiating the tissue graft with the electromagnetic radiation source. Claim 20 further comprises treating the wound with one of stromal vascular fraction, platelet rich plasma, fibrin, platelet-derived growth factor, TFG-beta, fibroblast growth factor, and epidermal growth factor after the steps of delivering, irradiating and activating.
The teachings of Loupis and Kislev are as discussed above. Loupis and Kislev do not specifically teach delivering the activating agent to the tissue graft, and irradiating the tissue graft with the electromagnetic radiation source, or treating the wound with one of stromal vascular fraction, platelet rich plasma, fibrin, platelet-derived growth factor, TFG-beta, fibroblast growth factor, and epidermal growth factor after the steps of delivering, irradiating and activating.
Austen teaches a method of preparing a non-adhesive tissue surface within a human subject by exposing an intact, non-proliferative, internal tissue surface located proximal to an incision in a human subject to a tissue structure stabilizing agent (TSSA) to promote cross-linking of proteins within the surface of the tissue, thereby preparing a non-adhesive tissue surface within the human subject. The tissue surface is located within a tissue such as connective, epithelial and muscle tissues etc. (e.g. [0010], [0011], claims 1-3). The tissue surface comprises previously grafted tissue (e.g. claim 4) (For claim 10). The TSSA is applied topically to the tissue surface and the TSSA is a photoactive agent or a chemical cross-linking compound (e.g. [0012], [0013], claims 5 and 7) (For claims 1-2). The TSSA is a photoactive agent and the method further comprises the step of irradiating the tissue surface at an irradiance of less than about 1 W/cm2 and the photoactive agent is Rose Bengal (RB) (e.g. [0014], claims 8-9 and 11- 12) (For claims 8 and 13). The irradiance is provided for a period between about 1 minute and 30 minutes or for less than about 5 minutes (e.g. [0015], claims 13-14) (For claims 4-5). Photoactive agents can be brushed, dripped or sprayed onto, or injected into, tissue surface prior to the application of electromagnetic energy and the electromagnetic radiation can be at an appropriate wavelength, energy and duration to cause passivation of the tissue surface. The wavelength can be from about 350 nm to about 800 nm, preferably from about 400 nm to about 700 nm, and the energy can be less than about 1 W/cm2 (e.g. [0099]) (For claims 3, 6-7 and 13). Suitable sources of electromagnetic energy can include lasers, lamps, light emitting diodes or other sources of electromagnetic radiation (e.g. [0101]) (For claim 9). Specific clinical applications also include passivation of tissue grafts and/or surgical sites to prevent contracture, scar contracture, capsular contracture around implants (e.g. [0110]). The passivated tissue graft refers to a tissue graft treated with a TSSA. Grafts thus passivated may be implanted into a subject to prevent or reduce stenosis in the subject (e.g. [0078]). Passivation of tissue prior to therapeutic use can be conducted according to the methods described herein to prepare improved tissue for therapeutic use (e.g. [0117]). Rose Bengal can be brushed onto tissue surfaces of a tissue prior to the application of electromagnetic energy, followed by irradiation at a irradiance of less than 1 W/cm2. Rose Bengal can be topically applied to a tissue graft and irradiating the tissue at an irradiance of less than about 1 W/cm2 (e.g. [0118]) (For claims 16-17). Tissue graft is prepared for implantation in a subject and the tissue graft comprises a tissue selected from the group consisting of vein, artery, bone, skin, muscle and cardiac tissue (e.g. [0034]) (For claims 18-19). A rabbit model for capsular contraction was developed. One model received Fibrin Gluc+RB+532 nm light. Fibrin is known to produce a fibrotic reaction in the model. The pockets treated with PTP prior to fibrin glue application had less infiltrates. These cells also appear contained under layers of presumably, cross- linked collagen (e.g. [0121]) (For claim 20). The skin graft and cardiac tissue would contain epithelial cells and smooth muscle cells, respectively (For claims 18-19).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to deliver the activating agent to the tissue graft, and irradiating the tissue graft with the electromagnetic radiation source because Austen teaches passivation of tissue graft with a TSSA such as Rose Bengal, and Rose Bengal can be topically applied to a tissue graft and irradiating the tissue at an irradiance of less than about 1 W/cm2, wherein the tissue graft is prepared for implantation in a subject. Both Loupis and Austen teach applying skin graft to the wound, and since Austen teaches Rose Bengal can be topically applied to a tissue graft and irradiating the tissue at an irradiance of less than about 1 W/cm2, wherein the tissue graft is prepared for implantation in a subject, it would be obvious for one of ordinary skill in the art to deliver the activating agent to the tissue graft taught by Loupis, and irradiating the tissue graft with the electromagnetic radiation source in order to optimize the healing effect and efficiency in non-healing wounds with reasonable expectation of success. Further, Austen teaches fibrin is known to produce a fibrotic reaction in the model and teaches treating rabbit model with Fibrin Glue+RB+532 nm light. It would be obvious for one of ordinary skill in the art to further treating the wound with fibrin in order to optimize the effect of wound-healing or to optimize the healing effect and efficiency in non-healing wounds with reasonable expectation of success. One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to promote and/or stimulate repair, or increase the rate of repair, in non-healing wounds or to stimulate and/or promote repair at the center and/or edge of a non-healing wound as taught by Loupis with reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
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, James (Doug) Schultz, can be reached at (571) 272-0763. 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.
MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631