DETIALED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 16 March 2026 has been entered.
Status of the Application
2. Claims 18-19 and 23-26 are pending and subject to examination on the merits.
Priority
3. Acknowledgement is made of applicant’s claim for foreign priority based on an application filed in AU AU2019903801 on 09 October 2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 16 March 2026 has been considered by the examiner. See initialed and signed PTO/SB/08’s.
Claim Interpretation
5. Claims 18, 23, and 24 have embedded within them, a product by process limitation. Therefore, Claim 18 and 23-24 are interpreted as a method for wound debridement, by administering to a subject a composition comprising one or more cysteine proteases with proteolytic activity that has been enhanced and/or stabilized, wherein the composition is obtained or obtainable by a method comprising contacting a protease with cysteine, wherein an active site cysteine is reduced, and combining the protease and a non-covalently bound carbomer. Therefore, the claim limitations of the first wherein clause of claim 18 and claims 23-24 will be searched to the extent required by product by process claims.
BIOGEN MA INC., v. EMD SERONO, INC., PFIZER INC., No. 19-1133 (Fed. Cir. 2020)
There is no logical reason why the nesting of a product-by-process limitation within a method of treatment claim should change how novelty of that limitation is evaluated……….The nesting of the product-by-process limitation within a method of treatment claim does not change the proper construction of the product-by-process limitation itself.
Maintained/Modified Rejection—necessitated by claim amendments
Claim Rejections - 35 USC § 103
6. 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.
7. 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.
8. Claim(s) 18-19 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al (Shi et al., 2016, US 20160008293 A1—cited previously), as evidenced by Alpha Chemistry (Alpha Chemistry, 2026, downloaded from < https://www.alfa-chemistry.com/resources/comprehensive-guide-to-carbomer-structure-functions-and-applications-in-pharmaceuticals-and-cosmetics.html> on 16 July 2026 as a PDF—cited herein) and Patel et al (Patel et al., 2011, BioProcess International—cited previously). Claim 18, 23-24, and 26, drawn to a method for the debridement of wounds by topically (claim 19) administering to a subject a composition comprising one or more cysteine proteases with proteolytic activity that has been enhanced and/or stabilized, wherein the composition is obtained or obtainable by a method comprising contacting a protease, specifically papain (claim 26), with cysteine, wherein an active site cysteine is reduced, removing substantially all oxygen gas from the area by degassing (claims 23-24) and combining the protease and a carbomer or a pharmaceutical formulation (claim 25) comprising the composition, wherein the composition or pharmaceutical formulation does not need to be reconstituted from a lyophilized form prior to use, Shi et al. teaches a method of treating wounds with a dissolvable, gel-forming film that releases enzyme actives into the wound site upon dissolving (paragraph 0003), wherein the gel-forming film has a water content of less than 15% w/w (higher than a lyophilized product) and forms a hydrogel when contacted with water for the uniform delivery of enzymes (abstract). Shi et al. continues to teach that the composition of its present invention can form hydrogels containing enzymes (paragraph 0039), and one of the enzymes suggested for release is papain, since there is historical utilization of papain (a cysteine protease) in wound debridement (paragraph 0044). Specifically, Shi et al. lists carbomer as an ingredient in the hydrogel-enzyme composition for wound debridement (p. 10, Example 2, Table 4), where said carbomer can interact with proteins via non-covalent binding, as evidenced by Alfa Chemistry (p. 8, Question 7). Regarding claim 19, drawn to the composition of claim 18 being applied topically, Shi et al. teaches the use of their dissolvable gel-forming films containing enzyme in would debridement, e.g. topical application (paragraph 0060). Regarding claim 25, drawn to the presence of a pharmaceutically acceptable excipient, Shi et al. teaches the use of hydrophilic rheological modifying agents, which are excipients, including PEG and other glycol-based materials, to vary the viscosity of the hydrogel (paragraph 0048).
Shi et al. does not teach one or more cysteine proteases which is in a reduced state.
Patel et al teaches the stabilization of proteolytic activity of cysteine proteases by the addition of antioxidants and metal chelating agents to prevent oxidation in protein formulations, wherein said antioxidants are chemical “sacrificial targets” with a strong tendency to oxidize, consuming chemical species that promote oxidation, and cysteine as a free amino acid may act as an effective antioxidant (p. 25, column 1, paragraph 3). Patel et al. continues to teach that protein stabilization is necessary because many physical and chemical factors can affect the quality and stability of biopharmaceutical products, and further that proteins are considerably larger molecular entities with inherent physiochemical complexities and can be sensitive to slight changes in solution chemistry (p. 20, column 1, paragraph 1 and column 2, paragraph 1).
Therefore, it would be obvious to combine the cysteine protease preparation methods of Patel et al. with the carbomer delivery composition of Shi et al. to treat wounds as taught by Shi et al. (paragraph 0005 and 0006) and to prevent the oxidation of cysteine by the addition of the antioxidant, cysteine, to protect the quality and overall stability of the biopharmaceutical product as taught by Patel et al. One would be motivated to combine the teachings of Patel et al. and Shi et al. to arrive at the instant claims because proteolytic enzymes can be used in wound debridement, facilitating the healing process, as taught by Shi et al. (paragraph 0006). Further, one would be motivated to add a reducing agent to the cysteine protease to ensure product safety and efficacy as taught by Patel et al (p. 20, column 1, paragraph 1). There would be a reasonable expectation of success, yielding no surprising results when combining the teachings of Shi et al. with Patel et al. because Shi et al. teaches the addition of a cysteine protease, papain, to carbomer to treat wounds, and Patel et al. teaches the addition of glutathione, a reducing agent, to enzymes to ensure their protection against degradation due to oxidation.
Applicant’s Arguments and Examiner’s Rebuttal:
The applicant traverses the previous rejection of record of Claims 18-19 and 23-25 over Shi et al. (Shi et al., 2016, 20160008293—cited previously) and Patel et al (Patel et al., 2011, BioProcess Ineternational—cited previously).
First, the applicant argues that Patel et al. fails to teach the present claims, specifically that Patel et al. does not teach cysteine proteases that are enhanced or stabilized. Rather, the applicant argues that Patel et al. teaches the stabilization of biotherapeutic proteins. The examiner agrees insofar that the Patel et al. teachings are not directed specifically to cysteine proteases; however, Patel et al. does teach the stabilization of therapeutic proteins and different methods are achieving stability, including utilizing cysteine as a free amino acid as an effective antioxidant (p. 25, 1st column), which necessarily would result in a reduced cysteine protease in the composition. Again it is noted, given parts (i)-(iii) of claim 18 are product by process limitations, and thus, the means to achieve a reduced state need not be the same. However, the examiner respectfully disagrees that the generic term, “biotherapeutic protein,” does not include cysteine proteases because as mentioned in the above rejection, papain, a cysteine protease, is conventionally used as a “biotherapeutic protein” for the debridement of wounds.
Second, the applicant argues that the proteins that are stabilized by Patel et al. have no proteolytic activity. The examiner respectfully disagrees. Patel et al. teaches general strategies to stabilize general proteins. There is no mention of one class of proteins over another. There may be examples embedded in the teachings, but again, there are no limiting examples and given Patel is a secondary reference, the teachings are in combination with Shi et al. who do teach cysteine proteases.
Third, the applicant argues that the only mention of proteases in the Patel et al. teachings is that of contaminants, and therefore, Patel et al. teaches against the use of proteases. The examiner respectfully disagrees with this assessment. Patel et al. mentions a common issue in protein purification of the presence of host cell proteases and the need to inhibit them to ensure the purification of a protein of interest (See Ryan and Henehan, 2013, Current Protocols in Protein Science—cited herein). This is a common issue in protein biology and does not constitute a teaching away or against the use of proteases as taught.
Fourth, the Applicant argues that the carbomer in combination with Bromelain teaches away from the use of carbomer. The examiner disagrees. The MPEP states that “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)… Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).” (See MPEP 2123 (II).
In the instant case, Shi et al. do not discredit, criticize, or otherwise discourage the use of carbomer. They simply state the other formulations performed in this particular assay better (Fig. 3), and at timepoint 25 of Fig. 4, there appears to be no difference between any of the formulations, since the error bars all overlap. Additionally, the bromelain gel was the only one that contained carbomer, and since it was the only one that contained carbomer, it is unclear that the gel failed because the carbomer or because of the other formulations. The examiner finds this line of reasoning unclear since there is no direct comparison with only carbomer being the differing trait between gels.
Last, the applicant argues that the formulation demonstrates unexpected and surprising results. However, the examiner respectfully disagrees. The general method of the claims is obviated by the above teachings of Shi et al. and Patel et al; therefore, as claimed, the method’s results would be expected and not surprising, since this result would be an inherent feature of the method itself.
The examiner does not find the arguments presented by the applicant persuasive, and for these reasons, the rejections of record above apply.
Conclusion
9. All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
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