DETAILED ACTION
Receipt is acknowledged of applicant’s Amendment/Remarks filed 8/19/2026.
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 8/19/2026 has been entered.
Status of the Claims
Claims 1-22, 29, 30, 32 and 34 are cancelled. No claims are amended or newly added. Accordingly, claims 23-28, 31, 33 and 35-44 remain pending in the application and are currently under examination.
Response to Declaration under 37 CFR 1.132
The Declaration under 37 CFR 1.132 filed 8/19/2026 is insufficient to overcome the rejection of claims 23-28, 31, 33, 35 and 39-44 under 35 USC 103 based upon Onsoyen and Shi ‘857 or rejection of claims 36 and 37 under 35 USC 103 based upon Onsoyen, Shi ‘857 and Sigma Aldrich as set forth in the last Office action for the following reasons:
The Declaration states that the research and development effort that led to Shi ‘857 was undertaken specifically to solve problems in enzymatic wound debridement, that is, the digestion and removal of eschar and other necrotic tissue from chronic and other wounds requiring debridement (para. 10). The Declaration also states that the “acute wounds” statement in [0054] of Shi ‘857 reflects standard, generic language of the type commonly included in patent specifications to describe a broad universe of wound types potentially amenable to topical treatment in general terms, and does not reflect any wound type, clinical indication, or use that was actually tested, investigated, or specifically intended by the inventors in developing the claimed film technology (para. 11). The Declaration further states that every formulation, dosing regimen, and experimental result reported in Shi ‘857 was directed to, and consistent with, the debridement of necrotic tissue (para. 11).
In response, it is acknowledged that Shi ‘857 explicitly states, “A wide variety of wounds can be treated with the films of the present invention. Examples include burns, acute wounds, or chronic wounds”. A reference is relevant for all that it contains and disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (MPEP 2123). While the Declaration attempts to explain that “acute wounds” were not intended to be within the scope of the invention of Shi ‘857, retroactively redefining a term or intended scope of a reference is not permissible. While Shi ‘857 teaches wound debridement of necrotic tissue from chronic wounds, Shi ‘857 also teaches treatment of acute wounds with the inventive films. Accordingly, the teachings of “acute wounds” in Shi ‘857 is relevant to the rejection and cannot be overcome by attempting to retroactively redefine a term or intended scope of Shi ‘857.
The Declaration further points to excerpts of Shi ‘857 that the technical problem the invention is designed to solve is around necrotic tissue, the working examples are to treating necrotic tissue, etc. (paras. 14-21). The Declaration asserts that a POSITA would understand that treating wounds having necrotic tissue is to which the invention’s methods are directed (paras. 14-21). The Declaration further states that a POSITA would understand the single reference to “acute wounds” in [0054] as an unsupported, isolated statement inconsistent with Shi ‘857’s actual technical disclosure would not have relied on the isolated statement as a basis for using Shi ‘857’s carrier system in the manner recited in pending claim 23 (paras. 22-30).
In response, a reference is relevant for all that it contains and disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (MPEP 2123). While Shi ‘857 teaches wound debridement of necrotic tissue from chronic wounds, Shi ‘857 also teaches treatment of acute wounds with the inventive films. Accordingly, a person of ordinary skill in the art would understand that treating acute wounds with the inventive films was contemplated by Shi ‘857 even if a particular embodiment or example is undisclosed. MPEP 716.07 and 2121 also state that prior art is presumed to be operable/enabling and it is the burden of applicant to rebut the presumption of operability by a preponderance of the evidence. It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker (MPEP 716.07). Further, if a patent teaches or suggests the claimed invention, an affidavit or declaration by patentee that they did not intend the disclosed invention to be used as claimed by applicant is immaterial (MPEP 716.07). The Declaration does not provide the requisite evidence that Shi ‘857 includes inoperable/non-enabling disclosure. Thus, the teachings of “acute wounds” in Shi ‘857 positively suggests the inventive films can be utilized for the treatment of acute wounds and, as such, said teaching is relevant to the rejection.
Maintained Rejections
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 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.
Claims 23-28, 31, 33, 35 and 39-44 stand rejected under 35 U.S.C. 103 as being unpatentable over Onsoyen et al. (USPN 8,680,072 B2, Mar. 25, 2014, hereafter as “Onsoyen”) in view of Shi et al. (WO 2014/150857 A1, Sep. 25, 2014, hereafter as “Shi ‘857”) as evidenced by Ather et al. (“Wound management and dressings”, Advanced Textiles for Wound Care, edited by S. Rajendran, Woodhead Publishing, 2009, pp. 3-19; hereafter as “Ather”).
The instant invention is drawn to a method of treating a surface on or within a surgical wound infected or contaminated with a bacterial biofilm, the method comprising administering to the surface a composition comprising thermolysin and a pharmaceutical carrier comprising two or more water-soluble cellulose ethers and a hydrophilic rheological modifying agent, wherein the surface on or within the surgical wound does not include necrotic tissue and is not in need of debridement, and wherein the bacterial biofilm is reduced or eliminated.
Regarding instant claims 23-28, Onsoyen teaches a method for combating biofilm said method comprising contacting a biofilm with an alginate oligomer, wherein the biofilm may be on an animate surface including internal body surfaces (e.g., oral cavity, the peritoneum, middle ear, urinary tract, vascular intima, conjunctiva, corneal tissue, respiratory tract, lung tissue, heart valves, gastrointestinal tract, skin, interior wounds and chronic wounds) or an inanimate surface including catheters (e.g., central venous and urinary catheters), prosthetic devices (e.g., heart valves, artificial joints), stents, pacemakers, etc. (abstract; col. 13, line 37- col. 14, line 11 and col. 14, lines 37-47). Onsoyen teaches that both chronic and acute wounds may be sites of biofilm infection (col. 3; lines 40-42). Onsoyen also teaches that the invention has the ability to treat and prevent biofilm and infection of wounds and is also effective in the promotion of healing of acute and chronic wounds (col. 17; lines 56-60). Onsoyen teaches that “combating biofilm” means “to include any effect in disrupting, reducing, or breaking down biofilm” and “encompasses the prevention of formation of a biofilm, the elimination of a biofilm, a reduction in biofilm size...” (col. 11, lines 5-25). Onsoyen further teaches the inclusion of other biofilm disrupting agent including proteases, e.g., metalloproteases and cites EP0590746 (incorporated by reference) for a list of suitable proteases (col. 21, lines 34-39). EP0590746 teaches the particular protease/metalloprotease, thermolysin (page 3, line 39). Onsoyen further teaches suitable pharmaceutically acceptable carriers including celluloses (col. 22, line 45). Onsoyen also teaches various suitable pharmaceutically acceptable carrier forms including suspensions, emulsions, solutions, aerosols (solid and liquid), sprays, ointments, powders, creams, gels, patches, etc. (col. 22, line 45 – col. 23, line 60). Additionally, Onsoyen does not require that the wound includes necrotic tissue or is in need of debridement (col. 14, lines 34-36; col. 22, lines 43-44).
While Onsoyen is silent to a particular embodiment drawn to a method of treating a surface on or within a surgical wound infected or contaminated with a bacterial biofilm, the method comprising administering to the surface a composition comprising the particular biofilm disrupting agent, thermolysin, 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 include thermolysin with a reasonably expectation of success because Onsoyen and EP0590746 (incorporated by reference) teach that proteases and in particular, thermolysin, is a suitable biofilm disrupter (MPEP 2144.07). A skilled artisan would reasonably expect a method for combating a biofilm, said method comprising applying to a surface on or within a surgical wound infected/contaminated with said biofilm a composition comprising an alginate oligomer and thermolysin.
Onsoyen is silent to a pharmaceutical carrier comprising two or more water-soluble cellulose ethers and a hydrophilic rheological modifying agent (instant claim 23), wherein the two or more water-soluble cellulose ethers comprises hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose (instant claim 43) and wherein the hydrophilic rheological modifying agent comprises polyethylene glycol (instant claim 44).
Shi ‘857 teaches a gel-forming film comprising a water-soluble cellulose ether, a hydrophilic rheological modifying agent, and an active proteolytic enzyme (e.g., thermolysin) or other drug substance for the purpose of treating wounds (abstract; [0002] and [0006]). Shi ‘857 teaches the particular cellulose ethers, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), or hydroxypropylmethylcellulose (HPMC), or any combination thereof or the combination of all of said cellulose ethers ([0007]). Shi ‘857 teaches the particular rheological modifying agent, polyethylene glycol ([0013]). Shi ‘857 further teaches particular embodiments comprising HEC and HPMC, polyethylene glycol and thermolysin ([0048]-[0050]; Tables 2-3 and 5). Shi ‘857 also teaches that the films achieve delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes (abstract). Shi ‘857 teaches that a wide variety of wounds can be treated including acute wounds and chronic wounds ([0054]). Shi teaches that presence of eschar and other necrotic tissue in a wound can impede the healing process, causing the wound to become a slow-healing or "chronic" wound ([0003]).
Additionally, acute wounds are understood in the art as “a recent wound that has yet to progress though the sequential stages of wound healing” and “is a result of an incision or trauma and heals in a timely and orderly manner” whereas chronic wounds are known as “wounds that fail to heal in an anticipated time frame and orderly fashion and often recur… venous leg ulcers, pressure ulcers and diabetic foot ulcers are some examples of chronic wounds as evidenced by Ather at sections 1.2.1-1.2.2.
Onsoyen and Shi ‘857 are both drawn to treating wounds including acute wounds (i.e, wounds that do not include necrotic tissue and are not in need of debridement) comprising administering a composition comprising thermolysin, thus, 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 include a particular formulation comprising a pharmaceutical carrier comprising two or more water-soluble cellulose ethers selected from HEC, HPC, and HPMC and a hydrophilic rheological modifying agent such as polyethylene glycol in the invention of Onsoyen, as suggested by Shi ‘857, with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Shi ‘857 teaches such a formulation comprising thermolysin is effective in achieving delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes for the purpose of treating wounds.
Regarding instant claims 31 and 33, Onsoyen teaches that the bacterial biofilm can contain gram positive or gram negative bacteria (col. 11, lines 50-55) and exemplifies the particular bacteria, Staphylococcus aureus and Pseudomonas aeruginosa (Examples).
Regarding instant claim 35, Onsoyen further cites EP0590746, incorporated by reference, which teaches that the proteases (e.g., thermolysin) are added in amounts that are effective to inhibit or remove a biofilm (page 4, lines 14-15). EP0590746 states that the precise dosage per se is not critical and may vary widely, but in general, 0.0001 U/mL to 100 U/mL wherein U is units of activity is suitable (page 4, lines 15-21).
Regarding instant claim 39, Onsoyen teaches that the alginate oligomers can be used in conjunction or in combination with an anti-microbial agent and particularly an antibiotic (col. 19, lines 52-56).
Regarding instant claim 40, Onsoyen, as discussed above, teaches various suitable pharmaceutically acceptable carrier forms including suspensions, emulsions, solutions, aerosols (solid and liquid), sprays, ointments, powders, creams, gels, patches, etc. (col. 22, line 45 – col. 23, line 60) and Shi ‘293 teaches a gel-forming film (abstract).
Regarding instant claim 41, it is noted that the claim includes the transitional phrase, “consisting essentially of”. For the purposes of searching for and applying prior art, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consisting essentially of” is construed as equivalent to “comprising”. It appears that the basic and novel characteristic of the claimed invention is compositions comprising thermolysin reduce or eliminate bacterial biofilms on surfaces ([0011] of instant specification). However, the method of the prior art does not appear to materially change the characteristics of Applicant’s invention. If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of “consisting essentially of”, Applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of Applicant’s invention. See MPEP 2111.03(III).
Regarding instant claim 42, it is noted the use of the transitional phrase, “consists of”. Onsoyen, as discussed above, teaches that the only required ingredient is an alginate oligomer and suggests the inclusion of thermolysin. Because no other ingredients are required, Onsoyen meets the limitations of the claim.
Thus, the teachings of Onsoyen in view of Shi ‘857 render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 8/19/2026, regarding the 103 rejection over Onsoyen and Shi ‘857 have been fully considered but they are not persuasive.
Applicant argues that Dr. Jovanovic, a named co-inventor of Shi ‘857 with first-hand, personal knowledge of its development, testifies that the research and development effort underlying Shi ‘857 was undertaken specifically to solve problems in enzymatic wound debridement, i.e., the digestion and removal of the eschar and other necrotic tissue, and was motivated by known shortcoming of existing debriding products (Declaration at para. 3). Dr. Jovanovic confirms that the statement in [0054] of Shi ‘857 – “[a] wide variety of wounds can be treated with the films of the present invention. Examples include burns, acute wounds, or chronic wounds” – reflects standard, generic language commonly included in patent specification to describe a broad universe of potentially treatable wound types in general terms, and does not reflect any wound type, indication, or use that was actually tested, investigated, or specifically invented by the inventors (Declaration at para. 11). Remarks, pages 5-6.
In response, it is respectfully submitted that it is acknowledged that Shi ‘857 explicitly states, “A wide variety of wounds can be treated with the films of the present invention. Examples include burns, acute wounds, or chronic wounds” [0054]. A reference is relevant for all that it contains and disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (MPEP 2123). While the Declaration attempts to explain that “acute wounds” were not intended to be within the scope of the invention of Shi ‘857, retroactively redefining a term or intended scope of a reference is not permissible. The intention of the inventors in Shi ‘857 is immaterial. If a patent teaches or suggests the claimed invention, an affidavit or declaration by patentee that they did not intend the disclosed invention to be used as claimed by applicant is immaterial (MPEP 716.07). The disclosure of the reference and what it suggests to a person of ordinary skill in the art is what is relevant to a prima facie case. While Shi ‘857 teaches wound debridement of necrotic tissue from chronic wounds, Shi ‘857 also teaches treatment of acute wounds with the inventive films. Accordingly, the teachings of “acute wounds” in Shi ‘857 is relevant to the rejection and cannot be overcome by attempting to retroactively redefine a term or intended scope of Shi ‘857.
Applicant argues that the Jovanovic Declaration also sets forth an independent technical analysis, from the perspective of a POSITA, confirming that Shi ‘857’s disclosure, considered as a whole, is directed exclusively to the enzymatic digestion of necrotic tissue and points to several excerpts of Shi ‘857. Remarks, pages 6-7.
In response, it is respectfully submitted that a reference is relevant for all that it contains and disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (MPEP 2123). While Shi ‘857 teaches wound debridement of necrotic tissue from chronic wounds and, admittedly, there is a heavy emphasis on treating necrotic tissue, nonetheless, Shi ‘857 also teaches treatment of acute wounds with the inventive films. Contrary to applicant’s assertions, it cannot be concluded that Shi ‘857 is directed exclusively to the enzymatic digestion of necrotic tissue. Such a conclusion is contradictory to the broader teachings of Shi ‘857. Accordingly, a person of ordinary skill in the art would understand that treating acute wounds with the inventive films was contemplated and suggested by Shi ‘857 even though no example as such is disclosed.
Applicant argues that a POSITA would understand that thermolysin, once active in a wound environment, will act indiscriminately on any accessible substrate proteins presenting the recognized residues, whether in necrotic or viable tissue. Applicant also asserts that Shi ‘857’s own formulation choices confirm that its carrier system is engineered to maximize, not limit proteolytic exposure; the specification teaches high enzyme loadings of 5 to 15% w/w, with worked examples at approximately 5% to nearly 12% w/w together with a carrier engineered to a viscosity that keeps the enzyme-laden hydrogel in continuous contact with the wound bed, and a therapeutic regimen of repeated reapplication continued until debridement is complete. Applicant asserts that this design contrasts with the antibiofilm mechanism of Onsoyen, which acts at the level of the biofilm matrix or embedded microbial cells without requiring digestion of the underlying host tissue, whereas Shi ‘857 achieves its entire measured effect through tissue-protein digestion. Remarks, pages 7-9.
In response, it is respectfully submitted that while Shi’857 teaches particular embodiments and examples related to treating wounds in need of debridement, Shi ‘857’s also provides broader teachings that applicant appears to be disregarding. A reference is relevant for all that it teaches (MPEP 2123). For example, Shi ‘857 teaches:
[0002] The invention generally relates to methods and compositions useful for treating wounds with a dissolvable, gel-forming film that releases enzyme actives onto the wound site upon dissolving.
[0006] The inventors provide a dissolvable, gel-forming film for delivering active agents, such as those used to treat wounds. The film is solid and non-flowable, but has the ability to dissolve upon contact with water or other aqueous medium (e.g., buffer or saline solution or from the wound itself) to form a hydrogel that remains on the wound, as described herein. This film solves the problems of (1) balancing enzyme activity and stability in a formulation that provides optimal conditions for enzyme function and (2) non-uniform delivery of the semisolid product, resulting in poor dose control. By way of example, a dissolvable, gel-forming film comprising a water-soluble ether, a hydrophilic rheological modifying agent, and a proteolytic enzyme (e.g., thermolysin) is provided. Such a composition is easily applied to a wound as a dry film, which is then dissolved with water or other aqueous medium to form a hydrogel and release the enzymes and/or other drug substances in active form and uniformly to the wounded area.
[0011] The dissolvable, gel-forming film may contain any weight percent of the proteolytic enzyme that one of ordinary skill in the art would choose to achieve a desired result. In some embodiments, the weight percent is not less than 0.1% of the dry weight of the film and does not decrease by more than 10% when stored at room temperature (defined as 20°C to 25 °C) for 24 months. In some embodiments, the film may contain a proteolytic enzyme in crystalline form. Emphasis added.
[0014] The dissolvable, gel- forming film may comprise any percentage of proteolytic enzyme. For example, the film may comprise 5 to 15% w/w of the proteolytic enzyme. In some aspects, the film comprises 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15%>, or any percentage derivable therein, w/w of the proteolytic enzyme. In some embodiments, the film may comprise a proteolytic enzyme in crystalline form. Emphasis added.
[0021] The terms "inhibiting," "reducing," "treating," or any variation of these terms, includes any measurable decrease or complete inhibition to achieve a desired result. For example, in certain embodiments, "treating" refers to a reduction in eschar on a wound. Similarly, the term "effective" means adequate to accomplish a desired, expected, or intended result. Emphasis added.
[0035] The inventors provide a dissolvable, gel-forming film for delivering active agents, such as those used to treat wounds. This film solves the problems of (1) balancing enzyme activity and stability in a formulation that provides optimal conditions for enzyme function and (2) non-uniform delivery of the semisolid product, resulting in poor dose control. By way of example, a dissolvable, gel-forming film comprising a water-soluble ether, a hydrophilic rheological modifying agent, and a proteolytic enzyme (e.g., thermolysin) is provided. Such a composition is easily applied to a wound as a dry film, which is then dissolved to form a hydrogel and to release the enzymes and/or other drug substances in active form and uniformly to the wounded area.
[0054] A wide variety of wounds can be treated with the films of the present invention. Examples include burns, acute wounds, or chronic wounds. Non-limiting examples of chronic wounds include diabetic foot ulcers, venous leg ulcers, arterial leg ulcers, decubitus ulcers, stasis ulcers, dermal ulcers, burns, and pressure ulcers.
MPEP 2123 also states that 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. When taken as a whole, Shi ‘857 suggests treating wounds, including acute wounds that do not include necrotic tissue and are not in need of debridement, with a composition comprising thermolysin and a carrier comprising two or more water-soluble cellulose ethers and a hydrophilic rheological modifying. Both Onsoyen and Shi ‘857 teach methods of treating acute wounds comprising administering thermolysin and that acute wounds encompass incision/surgical wounds. Additionally, Onsoyen teaches that celluloses are suitable carriers and Shi ‘857 teaches the specific celluloses, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), or hydroxypropylmethylcellulose (HPMC), or any combination thereof or the combination of all of said cellulose ethers. As such, both references teach that celluloses are suitable for the same purpose. Thus, contrary to applicant’s assertions, one of ordinary skill would look to Shi ‘857 to modify the teachings of Onsoyen. For these reasons, applicant’s argument is unpersuasive.
Applicant reiterates their position discussed in their Response filed 12/23/2025 that a POSITA would not have been motivated to modify Onsoyen’s antibiofilm composition to incorporate Shi ‘857’s carrier system because doing so would fundamentally alter Shi’ 857’s principle of operation. Applicant also reiterates that a POSITA would have no reasonable expectation of success. Applicant further states that Shi ‘857 does not disclose or suggest a lower enzyme concentration, shorter residence time, modified carrier rheology, or any other adjustment that would be needed to adapt its necrotic-tissue-digesting film for use on a viable surgical tissue. Applicant asserts that the prior art does not provide an indication of which parameters are critical nor direction as to which choices are likely to succeed in the claimed context. Remarks, pages 9-10.
In response, it is respectfully submitted that for the same reasons as discussed in the Office Action dated 5/19/2026 and the additional reasons discussed above as it relates to the Jovanovic Declaration, applicant’s argument is unpersuasive. The examiner’s position from said Office Action dated 5/19/2026 is reiterated below:
While the teachings of Shi ‘857 emphasize treating chronic wounds and appears to be a preferred embodiment, Shi ‘857 also teaches, “A wide variety of wounds can be treated with the films of the present invention. Examples include burns, acute wounds, or chronic wounds” ([0054]). Acute wounds are understood in the art as “a recent wound that has yet to progress though the sequential stages of wound healing” and “is a result of an incision or trauma and heals in a timely and orderly manner” whereas chronic wounds are known as “wounds that fail to heal in an anticipated time frame and orderly fashion and often recur… venous leg ulcers, pressure ulcers and diabetic foot ulcers are some examples of chronic wounds as evidenced by Ather at sections 1.2.1-1.2.2. MPEP 2123 states that references are relevant as prior art for all they contain including nonpreferred embodiments and that disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. MPEP 2123 also states that 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. Shi ‘857’s teachings encompass the treatment of acute wounds which are understood in the art as to heal in a timely and orderly manner which suggests that acute wounds are not necrotic and thereby do not require debridement. Both Onsoyen and Shi ‘857 teach methods of treating acute wounds comprising administering thermolysin and that acute wounds encompass incision/surgical wounds. Additionally, Onsoyen teaches that celluloses are suitable carriers and Shi ‘857 teaches the specific celluloses, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), or hydroxypropylmethylcellulose (HPMC), or any combination thereof or the combination of all of said cellulose ethers. 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 include the claimed celluloses in the biofilm combating composition of Onsoyen, as suggested by Shi ‘857, with a reasonable expectation of success because both references teach that celluloses are suitable for the same purpose, that is, to treat acute wounds. Furthermore, one of ordinary skill in the art would have been motivated make such a modification because Shi ‘857 teaches such a formulation comprising thermolysin is effective in achieving delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes for the purpose of treating wounds.
Additionally, contrary to applicant’s assertions that Shi ‘857’s teachings are narrow and directed to chronic wounds in need of debridement, Shi ‘857 provides broad teachings with respect to viscosity, film thickness, rate of dissolution, weight percent of proteolytic enzyme, concentration of water-soluble cellulose ether(s), amount of rheological modifying agent, etc. ([0007]-[0014]). It should be noted that the rejected claims do not require any of these elements nor has applicant/specification expressed that said elements are critical to the invention. Claims 36 and 37 are the only claims that include a thermolysin concentration, however said claims are rejected over Onsoyen, Shi ‘857 and Sigma Aldrich (see below) and are not relevant to the instant rejection. Further, applicant appears to be arguing that Shi ‘857 provides an inoperable/non-enabling disclosure for the acute wound embodiment. MPEP 716.07 and 2121 state that prior art is presumed to be operable/enabling and it is the burden of applicant to rebut the presumption of operability by a preponderance of the evidence. It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker (MPEP 716.07). It is also important to note that the expectation of success need only to be reasonable, not absolute (MPEP 2143.02). Applicant has not met their burden in providing the requisite evidence that Shi ‘857 includes an inoperable/non-enabling acute wound embodiment. The teachings of “acute wounds” in Shi ‘857 positively suggests the inventive films can be utilized for the treatment of acute wounds and, as such, said teaching is relevant to the rejection. Taken together, Onsoyen and Shi ‘857 provide the requisite teachings and motivation to arrive at the claimed invention and provide a prima facie case of obviousness. Applicant’s argument is unpersuasive.
Thus, for the above reasons, said rejection is maintained.
Claims 36 and 37 stand rejected under 35 U.S.C. 103 as being unpatentable over Onsoyen et al. (USPN 8,680,072 B2, Mar. 25, 2014, hereafter as “Onsoyen”) in view of Shi et al. (WO 2014/150857 A1, Sep. 25, 2014, hereafter as “Shi ‘857) as evidenced by Ather et al. (“Wound management and dressings”, Advanced Textiles for Wound Care, edited by S. Rajendran, Woodhead Publishing, 2009, pp. 3-19; hereafter as “Ather”), as applied to claim 23 above, and further in view of Sigma Aldrich’s product sheet for thermolysin (Jun. 29, 2015 via the Wayback machine; hereafter as “Sigma Aldrich”).
The instant claims are described above.
Onsoyen and Shi ‘857 teach the elements discussed above including amounts of proteases (e.g., thermolysin) that are effective to inhibit or remove a biofilm (EP0590746 at page 4, lines 14-15 incorporated by reference in Onsoyen) and that the precise dosage per se is not critical and may vary widely, but in general, 0.0001 U/mL to 100 U/mL wherein U is units of activity is suitable (page 4, lines 15-21).
Onsoyen and Shi ‘857 are silent to the particular concentration of thermolysin as being 0.00001 mg/mL to 10 mg/mL or 0.0001 mg/mL to 10 mg/mL (instant claims 36 and 37).
Sigma Aldrich teaches that thermolysin powder is supplied having 30-350 units/mg protein (title).
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 optimize the amount of thermolysin in Onsoyen/Shi ‘857 by way of routine experimentation and arrive at a concentration of 0.00001 mg/mL to 10 mg/mL or 0.0001 mg/mL to 10 mg/mL with a reasonable expectation of success because the prior art teaches that there is a wide variation of activity (30-350 units) per mg and a skilled artisan would have modified the amount of thermolysin until an optimal biofilm inhibiting/removing effect was achieved. One of ordinary skill would have reasonably expected a composition comprising an optimized amount of thermolysin effective in disrupting biofilms.
Thus, the combined teachings of Onsoyen, Shi ‘857 and Sigma Aldrich render the instant claims prima facie obvious.
Response to Arguments
Applicant's arguments, filed 8/19/2026, regarding the 103 rejection over Onsoyen, Shi ‘857 and Sigma Aldrich have been fully considered but they are not persuasive.
Applicant relies on the same arguments as presented for the 103 rejection over Onsoyen and Shi ‘857. Remarks, page 10.
For the same reasons as discussed above, Applicant’s arguments are not persuasive.
Applicant also argues, as previously stated in the Response filed 12/23/2025, that the cited references do not provide sufficient guidance for a POSITA to arrive at the claimed thermolysin concentration ranges without undue experimentation and no evidence of record establishes that the claimed ranges wound have been obvious to optimize through routine experimentation alone. Remarks, page 10.
As explained in the Office Action dated 5/19/2026, Onsoyen and Shi ‘857 teach amounts of proteases (e.g., thermolysin) that are effective to inhibit or remove a biofilm (EP0590746 at page 4, lines 14-15 incorporated by reference in Onsoyen) and that the precise dosage per se is not critical and may vary widely, but in general, 0.0001 U/mL to 100 U/mL wherein U is units of activity is suitable (page 4, lines 15-21). The references, as discussed above, also teach/suggest treating acute wounds/non-necrotic tissue. Sigma Aldrich additionally teaches that thermolysin powder is supplied having 30-350 units/mg protein (title). MPEP 2144.05 states,
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."
The references teach the general conditions of the claim and a skilled artisan would have been able to determine within the disclosed ranges of the prior art the optimal concentration(s) of thermolysin by way of routine experimentation. Further, applicant appears to be asserting that the claimed range is critical. If so, applicant’s attention is directed to MPEP 716.02(d)(II) and 2144.05(III)(A). At this time, no evidence has been provided that demonstrates criticality of the claimed range. Thus, Applicant’s arguments are found unpersuasive.
For these reasons, said rejection is maintained.
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 23-28, 31, 33 and 35-44 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7, 9-15 of U.S. Patent No. 11,628,207 B2 in view of Shi et al. (WO 2014/150857 A1, Sep. 25, 2014, hereafter as “Shi ‘857) and Onsoyen et al. (USPN 8,680,072 B2, Mar. 25, 2014, hereafter as “Onsoyen”).
The instant claims are described above.
The patented claims are drawn to a) a method of reducing or eliminating a bacterial biofilm on a biological surface, the method comprising administering to the biological surface a composition consisting of thermolysin and a pharmaceutically acceptable carrier, wherein the biological surface does not include necrotic tissue and is not in need of debridement, wherein the thermolysin is the only active ingredient in the composition that reduces or eliminates the biofilm, b) a method of reducing or eliminating a bacterial biofilm on a biological surface, the method comprising administering to the biological surface a composition consisting essentially of thermolysin and a pharmaceutically acceptable carrier, wherein the biological surface does not include necrotic tissue and is not in need of debridement, wherein the thermolysin is the only active ingredient in the composition that reduces or eliminates the biofilm, c) a method of treating a wound, mucous membrane lesion, or skin lesion infected or contaminated with a bacterial biofilm, the method comprising topically administering to the wound, mucous membrane lesion, or skin lesion a composition consisting of thermolysin and a pharmaceutically acceptable carrier, wherein the bacterial biofilm is reduced or eliminated, and wherein the wound, mucous membrane lesion, or skin lesion does not include necrotic tissue and is not in need of debridement, wherein thermolysin is the only active ingredient in the composition that reduces or eliminates the biofilm, and d) a method of treating a wound, mucous membrane lesion, or skin lesion infected or contaminated with a bacterial biofilm, the method comprising topically administering to the wound, mucous membrane lesion, or skin lesion a composition consisting essentially of thermolysin and a pharmaceutically acceptable carrier, wherein the bacterial biofilm is reduced or eliminated, and wherein the wound, mucous membrane lesion, or skin lesion does not include necrotic tissue and is not in need of debridement, wherein thermolysin is the only active ingredient in the composition that reduces or eliminates the biofilm. The patented claims further recite that the bacterial biofilm is a gram-positive bacterial biofilm or a gram-negative biofilm, the concentration of thermolysin is from 0.0001 mg/mL to 10 mg/mL, the biological surface is a skin lesion, a mucous membrane lesion, an internal organ, a body cavity, an oral cavity, a bone tissue, a muscle tissue, a nerve tissue, an ocular tissue, a urinary tract tissue, a lung tissue, a trachea tissue, a sinus tissue, an ear tissue, a dental tissue, a gum tissue, a nasal tissue, a vascular tissue, a cardiac tissue, an epithelium tissue, an epithelial lesion, a vaginal tissue, or a peritoneal tissue, and the pharmaceutically acceptable carrier comprises a lotion, solution, suspension, liquid, emulsion, cream, gel, hydrogel, ointment, paste, aerosol spray, aerosol foam, non-aerosol spray, non-aerosol foam, film, powder, or sheet. It is noted that the patent defines “wound” to include acute wounds including surgical wounds (col. 6, lines 22-24 and col. 11, lines 17-62).
The patent does not recite, a pharmaceutical carrier comprising two or more water-soluble cellulose ethers and a hydrophilic rheological modifying agent (instant claim 23), wherein the two or more water-soluble cellulose ethers comprises hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose (instant claim 43) and wherein the hydrophilic rheological modifying agent comprises polyethylene glycol (instant claim 44).
Shi ‘857 teaches a gel-forming film comprising a water-soluble cellulose ether, a hydrophilic rheological modifying agent, and an active proteolytic enzyme (e.g., thermolysin) or other drug substance for the purpose of treating wounds (abstract; [0002] and [0006]). Shi ‘857 teaches the particular cellulose ethers, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), or hydroxypropylmethylcellulose (HPMC), or any combination thereof or the combination of all of said cellulose ethers ([0007]). Shi ‘857 teaches the particular rheological modifying agent, polyethylene glycol ([0013]). Shi ‘857 further teaches particular embodiments comprising HEC and HPMC, polyethylene glycol and thermolysin ([0048]-[0050]; Tables 2-3 and 5). Shi ‘857 also teaches that the films achieve delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes (abstract). Shi ‘857 teaches that a wide variety of wounds can be treated including acute wounds and chronic wounds ([0054]). Shi teaches that presence of eschar and other necrotic tissue in a wound can impede the healing process, causing the wound to become a slow-healing or "chronic" wound ([0003]).
The patent and Shi ‘857 are both drawn to treating acute (non-necrotic or in need of debridement) wounds comprising administering a thermolysin composition, thus, 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 include a particular formulation comprising a pharmaceutical carrier comprising two or more water-soluble cellulose ethers selected from HEC, HPC, and HPMC and a hydrophilic rheological modifying agent such as polyethylene glycol in the patent as suggested by Shi ‘857 with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Shi ‘857 teaches such a formulation comprising thermolysin is effective in achieving delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes for the purpose of treating acute wounds.
The patented claims do not recite non-biological surfaces.
Onsoyen teaches a method for combating biofilm said method comprising contacting a biofilm with an alginate oligomer, wherein the biofilm may be on an animate surface including internal body surfaces (e.g., oral cavity, the peritoneum, middle ear, urinary tract, vascular intima, conjunctiva, corneal tissue, respiratory tract, lung tissue, heart valves, gastrointestinal tract, skin, interior wounds and chronic wounds) or an inanimate surface including catheters (e.g., central venous and urinary catheters), prosthetic devices (e.g., heart valves, artificial joints), stents, pacemakers, etc. (abstract; col. 13, line 37- col. 14, line 11 and col. 14, lines 37-47). Onsoyen further teaches the inclusion of other biofilm disrupting agent including proteases, e.g., metalloproteases and cites EP0590746 (incorporated by reference) for a list of suitable proteases (col. 21, lines 34-39). EP0590746 teaches the particular protease/metalloprotease, thermolysin (page 3, line 39).
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 include nonbiological surfaces such as catheters, prosthetic devices, stents, pacemakers, etc. with a reasonable expectation of success because Onsoyen teaches biofilm disrupting compositions that can contain thermolysin are effective on both biological surfaces and nonbiological surfaces.
Thus, the subject matter of the instant claims is unpatentable over the subject matter of the patented claims in view of Shi ‘857 and Onsoyen.
Claims 23-28, 31, 33, 35-37 and 39-44 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 12-14 of U.S. Patent No. 11,413,300 B2 in view of Shi et al. (WO 2014/150857 A1, Sep. 25, 2014, hereafter as “Shi ‘857) and Onsoyen et al. (USPN 8,680,072 B2, Mar. 25, 2014, hereafter as “Onsoyen”).
The instant claims are described above.
The patented claims are drawn to a method of treating a biological surface infected or contaminated with a bacterial biofilm or reducing or eliminating a bacterial biofilm on a biological surface, the method comprising administering to the biological surface a composition comprising a combination of thermolysin and gentamicin (antibacterial) or a salt form thereof, wherein the concentrations of thermolysin and gentamicin in the composition are at amounts effective to reduce or eliminate the bacterial biofilm on the biological surface. The patented claims further recites the concentration of thermolysin is 0.1 to 1% w/w, inclusion of a carrier such as a lotion, solution, suspension, liquid, emulsion, cream, gel, ointment, paste, aerosol spray, aerosol foam, non-aerosol spray, non-aerosol foam, film, or sheet, the bacterial biofilm comprises gram-positive and/or gram-negative bacterial species, chronic wounds, and biological surfaces including an internal organ, a body cavity, an oral cavity, a bone tissue, a muscle tissue, a nerve tissue, an ocular tissue, a urinary tract tissue, a lung tissue, a trachea tissue, a sinus tissue, an ear tissue, a dental tissue, a gum tissue, a nasal tissue, a vascular tissue, a cardiac tissue, an epithelium tissue, an epithelial lesion, a vaginal tissue, or a peritoneal tissue. It is noted that the patent defines “wound” to include acute wounds including surgical wounds (col. 15, lines 1-3, col. 24, lines 48-50 and col. 25, lines 4-5).
The patent does not recite, a pharmaceutical carrier comprising two or more water-soluble cellulose ethers and a hydrophilic rheological modifying agent (instant claim 23), wherein the two or more water-soluble cellulose ethers comprises hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose (instant claim 43) and wherein the hydrophilic rheological modifying agent comprises polyethylene glycol (instant claim 44).
Shi ‘857 teaches a gel-forming film comprising a water-soluble cellulose ether, a hydrophilic rheological modifying agent, and an active proteolytic enzyme (e.g., thermolysin) or other drug substance for the purpose of treating wounds (abstract; [0002] and [0006]). Shi ‘857 teaches the particular cellulose ethers, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), or hydroxypropylmethylcellulose (HPMC), or any combination thereof or the combination of all of said cellulose ethers ([0007]). Shi ‘857 teaches the particular rheological modifying agent, polyethylene glycol ([0013]). Shi ‘857 further teaches particular embodiments comprising HEC and HPMC, polyethylene glycol and thermolysin ([0048]-[0050]; Tables 2-3 and 5). Shi ‘857 also teaches that the films achieve delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes (abstract). Shi ‘857 teaches that a wide variety of wounds can be treated including acute wounds and chronic wounds ([0054]). Shi teaches that presence of eschar and other necrotic tissue in a wound can impede the healing process, causing the wound to become a slow-healing or "chronic" wound ([0003]).
The patent and Shi ‘857 are both drawn to treating acute (non-necrotic or in need of debridement) wounds comprising administering a thermolysin composition, thus, 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 include a particular formulation comprising a pharmaceutical carrier comprising two or more water-soluble cellulose ethers selected from HEC, HPC, and HPMC and a hydrophilic rheological modifying agent such as polyethylene glycol in the patent as suggested by Shi ‘857 with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Shi ‘857 teaches such a formulation comprising thermolysin is effective in achieving delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes for the purpose of treating acute wounds.
The patented claims do not recite non-biological surfaces.
Onsoyen teaches a method for combating biofilm said method comprising contacting a biofilm with an alginate oligomer, wherein the biofilm may be on an animate surface including internal body surfaces (e.g., oral cavity, the peritoneum, middle ear, urinary tract, vascular intima, conjunctiva, corneal tissue, respiratory tract, lung tissue, heart valves, gastrointestinal tract, skin, interior wounds and chronic wounds) or an inanimate surface including catheters (e.g., central venous and urinary catheters), prosthetic devices (e.g., heart valves, artificial joints), stents, pacemakers, etc. (abstract; col. 13, line 37- col. 14, line 11 and col. 14, lines 37-47). Onsoyen further teaches the inclusion of other biofilm disrupting agent including proteases, e.g., metalloproteases and cites EP0590746 (incorporated by reference) for a list of suitable proteases (col. 21, lines 34-39). EP0590746 teaches the particular protease/metalloprotease, thermolysin (page 3, line 39).
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 include nonbiological surfaces such as catheters, prosthetic devices, stents, pacemakers, etc. with a reasonable expectation of success because Onsoyen teaches biofilm disrupting compositions that can contain thermolysin are effective on both biological surfaces and nonbiological surfaces.
Thus, the subject matter of the instant claims is unpatentable over the subject matter of the patented claims in view of Shi ‘857 and Onsoyen.
Claims 23-28, 31, 33, 35-37 and 39-44 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-14 of U.S. Patent No. 11,957,698 B2 in view of Shi et al. (WO 2014/150857 A1, Sep. 25, 2014, hereafter as “Shi ‘857) and Onsoyen et al. (USPN 8,680,072 B2, Mar. 25, 2014, hereafter as “Onsoyen”).
The instant claims are described above.
The patented claims are drawn to a composition comprising a combination of 0.1 to 1% (w/w) thermolysin and 0.1 to 1% (w/w) gentamicin or a salt form thereof based on the total weight of the composition, and a pharmaceutically acceptable carrier suitable for application to a biological surface, wherein the composition is capable of reducing or eliminating a bacterial biofilm on a biological surface when the composition is in direct contact with the biological surface. The patented claims further recite the inclusion of a carrier such as a lotion, solution, suspension, liquid, emulsion, cream, gel, ointment, paste, aerosol spray, aerosol foam, non-aerosol spray, non-aerosol foam, film, or sheet, the bacterial biofilm comprises gram-positive and/or gram-negative bacterial species, acute wounds, and biological surfaces including an internal organ, a body cavity, an oral cavity, a bone tissue, a muscle tissue, a nerve tissue, an ocular tissue, a urinary tract tissue, a lung tissue, a trachea tissue, a sinus tissue, an ear tissue, a dental tissue, a gum tissue, a nasal tissue, a vascular tissue, a cardiac tissue, an epithelium tissue, an epithelial lesion, a vaginal tissue, or a peritoneal tissue, and the composition comprises a water-soluble cellulose ether. It is noted that the patent defines “wound” to include acute wounds including surgical wounds (col. 15, lines 19-21, col. 25, lines 4-6 and 27-28).
The patent does not recite, a pharmaceutical carrier comprising two or more water-soluble cellulose ethers and a hydrophilic rheological modifying agent (instant claim 23), wherein the two or more water-soluble cellulose ethers comprises hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose (instant claim 43) and wherein the hydrophilic rheological modifying agent comprises polyethylene glycol (instant claim 44).
Shi ‘857 teaches a gel-forming film comprising a water-soluble cellulose ether, a hydrophilic rheological modifying agent, and an active proteolytic enzyme (e.g., thermolysin) or other drug substance for the purpose of treating wounds (abstract; [0002] and [0006]). Shi ‘857 teaches the particular cellulose ethers, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), or hydroxypropylmethylcellulose (HPMC), or any combination thereof or the combination of all of said cellulose ethers ([0007]). Shi ‘857 teaches the particular rheological modifying agent, polyethylene glycol ([0013]). Shi ‘857 further teaches particular embodiments comprising HEC and HPMC, polyethylene glycol and thermolysin ([0048]-[0050]; Tables 2-3 and 5). Shi ‘857 also teaches that the films achieve delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes (abstract). Shi ‘857 teaches that a wide variety of wounds can be treated including acute wounds and chronic wounds ([0054]). Shi teaches that presence of eschar and other necrotic tissue in a wound can impede the healing process, causing the wound to become a slow-healing or "chronic" wound ([0003]).
The patent and Shi ‘857 are both drawn to treating acute wounds (non-necrotic and not needing debridement) comprising administering a thermolysin composition, thus, 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 include a particular formulation comprising a pharmaceutical carrier comprising two or more water-soluble cellulose ethers selected from HEC, HPC, and HPMC and a hydrophilic rheological modifying agent such as polyethylene glycol in the patent as suggested by Shi ‘857 with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Shi ‘857 teaches such a formulation comprising thermolysin is effective in achieving delivery of stable proteolytic enzymes to the desired site of action in a manner that provides uniform delivery of the enzymes for the purpose of treating acute wounds.
The patented claims also do not recite non-biological surfaces.
Onsoyen teaches a method for combating biofilm said method comprising contacting a biofilm with an alginate oligomer, wherein the biofilm may be on an animate surface including internal body surfaces (e.g., oral cavity, the peritoneum, middle ear, urinary tract, vascular intima, conjunctiva, corneal tissue, respiratory tract, lung tissue, heart valves, gastrointestinal tract, skin, interior wounds and chronic wounds) or an inanimate surface including catheters (e.g., central venous and urinary catheters), prosthetic devices (e.g., heart valves, artificial joints), stents, pacemakers, etc. (abstract; col. 13, line 37- col. 14, line 11 and col. 14, lines 37-47). Onsoyen further teaches the inclusion of other biofilm disrupting agent including proteases, e.g., metalloproteases and cites EP0590746 (incorporated by reference) for a list of suitable proteases (col. 21, lines 34-39). EP0590746 teaches the particular protease/metalloprotease, thermolysin (page 3, line 39).
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 include nonbiological surfaces such as catheters, prosthetic devices, stents, pacemakers, etc. with a reasonable expectation of success because Onsoyen teaches biofilm disrupting compositions that can contain thermolysin are effective on both biological surfaces and nonbiological surfaces.
While the patent does not recite the limitations, “a method of treating a surface… comprising administering to the surface”, the patent recites “the composition is capable of reducing or eliminating a bacterial biofilm on a biological surface when the composition is in direct contact with the biological surface”. Thus, 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 include the method of using the composition comprising applying said composition with a reasonable expectation of success because the patent recites that contact of the composition with the biological surface would accomplish treatment/reduction/elimination of a bacterial biofilm on a biological surface including acute surgical wounds.
Thus, the subject matter of the instant claims is unpatentable over the subject matter of the patented claims in view of Shi ‘857 and Onsoyen.
Response to Arguments
Applicant's arguments, filed 8/19/2026, regarding the double patenting rejections over USPN 11,628,207 in view of Shi ‘857 and Onsoyen; USPN 11,413,300 in view of Shi ‘857 and Onsoyen; and USPN 11,957,698 in view of Shi ‘857 and Onsoyen have been fully considered but they are not persuasive.
Applicant asserts that the pending claims are patentable over Shi ‘857 and Onsoyen for the same reasons as discussed in the 103 rejections above. Remarks, pages 10-11.
In response, it is respectfully submitted that for the same reasons as discussed above, applicant’s arguments regarding Shi ’857 and Onsoyen are not persuasive.
Thus, the double patenting rejections are still applicable.
Conclusion
All claims have been rejected; no claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CASEY HAGOPIAN whose telephone number is (571)272-6097. The examiner can normally be reached on M-F 9:00 am - 5:00 pm.
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Casey S. Hagopian
Examiner, Art Unit 1617
/CARLOS A AZPURU/Primary Examiner, Art Unit 1617
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