DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
The amendment of 05/20/2026 has been entered. Claims 1 and 3-20 are currently pending in this US patent application and were examined on their merits.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1 and 3-20 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. patent application publication 2009/0263468 filed by McAnulty et al., published 10/22/2009, in view of US patent application publication 2003/0198632 filed by Shi et al., published 10/23/2003.
Please note that this rejection has been slightly augmented to incorporate discussion of the newly added limitation to amended claim 1 in the response of 05/20/2026. However, because the basis of the rejection is unchanged, the rejection has been maintained.
McAnulty teaches methods and compositions for the modulation of wound healing (see entire document, including page 1, paragraph 0002). The methods comprise applying to a wound on a subject an article comprising a matrix formed from a biocompatible material containing at least one wound active agent (page 7, paragraph 0035; cf. claim 16). The matrix may be at least partially PEGylated (page 7, paragraph 0035; cf. claims 8-9) and may be contained within a sterile package (page 7, paragraph 0035; cf. claim 15). The wound active agent may be a protease, such as papain or collagenase (page 19, paragraph 0141; cf. claims 1 and 3-5; the Examiner notes that the existence of a protein in an aqueous solution as either solubilized, suspended, or a mixture of both would depend on the identity of the protein and its concentration and that any protein in a composition containing water would intrinsically contain at least one solubilized protein molecule and one suspended protein molecule; the Examiner further notes that McAnulty teaches that the term “aqueous solutions” includes solutions, suspensions, and dispersions [page 9, paragraph 0064]; the Examiner further notes that any such matrix containing a protease could be interpreted as an “active phase” as recited in instant claim 1). The matrix may contain hydroxyethylcellulose (page 27, paragraph 0177; cf. claims 1 and 7). The matrix may be a hydrogel (page 28, paragraph 0180; cf. claim 1; the Examiner notes that hydrogels intrinsically contain water; the Examiner further notes that a hydrogel matrix containing hydroxyethylcellulose is intrinsically an “aqueous continuous phase containing water gelled with a nonionic cellulose ether” because the water is gelled and hydroxyethylcellulose is present, satisfying “with” as recited, and the presence of the protease within the matrix would intrinsically be “an active phase dispersed in the continuous phase”). Compositions applied to wounds may contain phosphate buffered saline and be at a pH of 7.6 (page 31, paragraph 0208; cf. claims 8 and 11-12). The compositions may be used on all types of wounds (page 30, paragraph 0197), including chronic wounds (page 9, paragraph 0068; cf. claim 18), burns, and ulcers (page 30, paragraph 0197; cf. claim 19).
However, McAnulty does not teach the stability limitations recited in instant claims 1, 13, and 14, that the protease is thermolysin, or the protease concentration recited in claim 1.
Shi teaches that papain is a commonly used debridement enzyme but it is nonspecific, has stability issues, and has a characteristic odor (see entire document, including page 1, paragraph 0005). Thermolysin, in contrast, has higher collagenolysis and fibrolysis activity than papain and is highly thermostable, allowing it to be stored at room temperature with a longer shelf life (pages 1-2, paragraph 0013; cf. claim 6). Thermolysin preparations can be in the form of gels (page 2, paragraph 0013). Thermolysin preparations can be used to debride necrotic tissue in chronic wounds (page 2, paragraph 0014; cf. claims 17 and 20). An aqueous thermolysin cream containing 1% thermolysin and methylparaben as a preservative showed a decline in thermolysin activity of only ~15% upon storage at room temperature for three months (page 2, paragraphs 0019-0021; Figure 4; cf. claims 1, 10, and 13-14).
While McAnulty does not teach that the proteolytic enzyme in the method of applying hydrogel matrices containing hydroxyethylcellulose and papain to any wounds, including chronic wounds, burns, and ulcers, rendered obvious by their teachings is thermolysin, it would have been obvious to one of ordinary skill in the art to do so because Shi teaches that thermolysin is more effective at debriding wounds than papain and is more stable. One of ordinary skill in the art would have a reasonable expectation that incorporating the thermolysin of Shi in the hydrogel matrix of McAnulty would successfully result in the increased stability of the composition and the ability to more effectively debride wounds, including chronic wounds containing necrotic tissue.
While McAnulty and Shi do not teach the specific stability limitations recited in claims 1 and 13-14, the Examiner notes that it is well-known in the art that the stability of an enzyme is strongly influenced by the concentrations and identities of the other components of the enzyme-containing composition, which would have been within the realm of routine experimentation. Generally, differences in concentration 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05 part II A. It would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal concentrations of the ingredients of the thermolysin-containing hydrogel, such as salts and buffers, because the concentrations of the ingredients in an enzyme composition are art-recognized, result-effective variables known to affect the stability of the enzyme, which would have been optimized in the art to provide the desired level of stability.
Therefore, claims 1 and 3-20 are rendered obvious by McAnulty in view of Shi and are rejected under 35 U.S.C. 103(a).
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant has traversed the above rejection of the claims under 35 U.S.C. 103(a) as being unpatentable over McAnulty in view of Shi. Applicant states that McAnulty does not teach a single embodiment in which an aqueous hydrogel is gelled with HEC or a reason to select HEC from the list of 13 polymers in paragraph 0177. Applicant states that the Examiner has combined different embodiments in paragraphs 0141, 0177, and 0180 of McAnulty without providing a reason why one of ordinary skill in the art would do so (remarks, pages 4-5). This argument has been fully considered but has not been found persuasive.
The Examiner notes that instant claim 1 recites that the hydrogel “comprises an aqueous continuous phase comprising water gelled with a nonionic cellulose ether” (emphasis added). The open-ended nature of this limitation does not preclude the inclusion of additional ingredients in the hydrogel, such as proteins. This limitation also does not in any way preclude the hydrogel from having multiple layers. All that is required by this limitation is a phase that is a hydrogel containing water and a nonionic cellulose ether, which are all taught by McAnulty. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Regarding Applicant’s assertion that the cited portions of McAnulty represent separate embodiments and Applicant’s assertion that one of ordinary skill in the art would not have been motivated to select HEC from a list of 13 polymers, the Examiner notes that references are prior art for all they contain, not merely for preferred embodiments. See MPEP § 2123. McAnulty in no way teaches, suggests, implies, or makes any sort of intimation whatsoever that its embodiments can somehow not be combined together. Any combination of any of the elements recited by McAnulty would be obvious to one of ordinary skill in the art because McAnulty suggests all of them for the modulation of wound healing. One of ordinary skill in the art would be motivated to select any of the polymers suggested by McAnulty because McAnulty suggests all of them for forming a composition for the modulation of wound healing.
Applicant states that McAnulty does not teach the “affirmatively recited formulation architecture” in amended claim 1 in which an active phase is dispersed within an aqueous continuous phase comprising water gelled with a nonionic cellulose ether or the gelling of water with hydroxyethyl cellulose (remarks, page 6). This argument has been fully considered but has not been found persuasive.
The Examiner notes that the instant claims require the application to a surface of a composition the following ingredients: 1) a hydrogel comprising an aqueous continuous phase comprising “water gelled with a nonionic cellulose ether” (the Examiner notes that the wording of this limitation requires only that the hydrogel comprise a) water that has been gelled and b) a nonionic cellulose ether because if both a) and b) are present in the composition, they are “with” each other), and 2) an active phase that comprises a certain amount of protease and is “dispersed in the continuous phase.” The claim does not require that the active phase be in contact with the gelled water or with the nonionic cellulose ether, nor does the claim require that the “active phase” and the “continuous phase” have any structural distinction from one another. McAnulty suggests all of these limitations, as discussed extensively above. As such, McAnulty suggests the “affirmatively recited formulation architecture” that is present in Applicant’s claim. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant states Shi does not cure the alleged deficiencies of McAnulty (remarks, page 6). This argument has been fully considered but has not been found persuasive because the Examiner does not agree with Applicant’s assertions of McAnulty’s deficiencies.
Applicant states that the Office has not sufficiently articulated reasons why a hydrogel comprising a protease in the specifically recited concentration range would have been obvious and that the unpredictability of enzyme stability in light of the ingredients of an enzyme-containing composition undermines the applicability of In re Aller in the instant case. Applicant states that Shi teaches a cream, which is different from a hydrogel, and teaches only a single concentration instead of the instantly recited concentration range. Applicant states that their specification confirms that the claimed formulation is not a mere optimization of known variables because the specific thermolysin/HEC hydrogel of paragraphs 0057-0064 of the instant specification as filed unexpectedly retained activity after room-temperature storage (remarks, pages 7-8). These arguments have been fully considered but have not been found persuasive.
The Examiner notes that, as discussed above, Shi teaches a concentration of thermolysin in a composition that falls within Applicant’s claimed concentration range, which is sufficient for prima facie obviousness over the range (see MPEP § 2144.05). Regarding the alleged unpredictability of the stability of an enzyme in a formulation, the Examiner notes that obviousness under 35 U.S.C. 103 does not require an absolute certainty of success but, rather, a reasonable expectation of success. Given the extraordinarily routine nature of performing enzyme assays on enzyme-containing formulations (regardless of whether they are hydrogels or creams or any other form factor) to determine the effects of various components of the formulation on the activity and stability of the enzyme, the Examiner does not concur with Applicant’s assertion that In re Aller is not applicable to the instant case but, rather, maintains that the routine nature of such optimization and the known sensitivity of enzymes to other compounds strongly supports the idea that such optimization would have been routine to one of ordinary skill in the art.
The Examiner further notes that the specific embodiment of a highly specific hydrogel comprising thermolysin and HEC recited in paragraphs 0057-0064 of the instant specification is significantly narrower than the hydrogel comprising a protease and a nonionic cellulose ether recited in instant claim 1. The specific structure of the formulation of paragraphs 0057-0064 of the instant specification, which it appears Applicant is arguing is responsible for the allegedly unexpected stability of the formulation, is not recited in or required by the instant claims. As such, these results are not commensurate in scope with the instant claims. See MPEP § 716.02(d).
Therefore, the Examiner has maintained the rejections presented above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau, can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 07/19/2026
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