DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Priority to US 63/694,835, filed 9/14/2024, is acknowledged.
Claim Status
Claims 1-20, filed 6/17/2026, are pending. Claims 1-20 are under examination.
Maintained Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4, 8, 9, and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over León-López et al. (León-López,et al. Molecules 24.22: 4031 (2019)) in view of Mayandi et al. (Mayandi, Venkatesh, et al. ACS applied materials & interfaces 12.14: 15989-16005 (2020)) as evidenced by Daneault et al. (Daneault, et al. Critical Reviews in Food Science and Nutrition 57.9: 1922-1937 (2017)).
León-López discloses antibacterial hydrogels for wound healing comprising hydrolyzed collagen: “Hydrogels prepared with chitosan and fish HC showed antibacterial activity against Escherichia coli, Staphylococcus aureus, pro-cell proliferation and migration, and wound healing
efficiency.” (León-López,et al., page 9, para. 1).
León-López does not disclose polylysine at a weight % of 0.01 to 50%. However, Mayandi discloses that ε-polylysine is an effective antimicrobial agent:” The emergence of antibiotic-resistance bacteria, together with an increased frequency of application of topical biocides, which are toxic to dermal cells, creates a need for new antimicrobial agents with improved cell selectivity. (26,27) Among polymers of various structural diversity that target the cytoplasmic membrane of bacteria, εPL displayed superior selectivity in targeting microbial membrane over mammalian cell membrane both in vitro and in vivo. Thus, we investigated the antimicrobial properties of εPL against a panel of antibiotic-resistant and antibiotic susceptible pathogens. The panel includes 185 pathogens that include MRSA, vancomycin-resistant Enterococcus faecium (VRE), carbapenem-resistant Enterobacteriaceae (CRE), colistin-resistant E. coli, multi-drug resistant P. aeruginosa, and fluconazole-resistant Candida spp. For a number of Gram-negative and Gram-positive strains, the MIC values ranged from 8 to 32 μg/mL with an MIC90 value of 32 μg/mL (Figure1A). Mean MIC values against various bacteria and yeasts strains are shown in Table S1. When compared to bacteria, higher mean MICs was observed for Candida strains, suggesting the possible role played by the thick chitin cell wall in protecting the cytoplasmic membrane from the cationic polymer.” (Mayandi et al., page 15991, col. 1, para. 1).
Mayandi discloses a 10% w/w ε-polylysine composition:” A homogeneous gelatin solution (10% w/v) was prepared in 90% TFE containing εPL (10% w/w of gelatin) and dopamine hydrochloride (2% w/w of gelatin) and incubated overnight with gentle stirring. The concentration of εPL was chosen so that the crosslinked mats displayed ≥4 log10 decrease in the viability of bacterial strains after 24 h exposure.” (Mayandi et al., page 16000, col. 2, para. 2).
Daneault discloses that gelatin and hydrolyzed collagen have the same composition:
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(Daneault et al., page 1924, Fig. 2).
Mayandi discloses that the crosslinking of gelatin occurs at -NH2 and -C=O moieties of gelatin and εPL :“The origin of increased C═N bonds and decreased C═O bonds could be explained by the generation of additional aldimine bonds (C═N bonding) upon (i) reaction of the −C═O functional groups of dopamine and −NH2 functional groups of gelatin upon crosslinking and (ii) covalent interaction of −NH2 and −C═O moieties of εPL with gelatin and dopamine. (49)”. (Mayandi et al., page 15993, col. 2, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the hydrolyzed collagen of León-López with the polylysine molecule disclosed by Mayandi to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to combine hydrolyzed collagen with ε-polylysine both because compositions have antimicrobial properties and MPEP 2144.06(I) states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would also be motivated to add additional antimicrobial activity to the wound treatment disclosed by León-López to further preclude infection at a wound being treated by said treatment.
A person of ordinary skill in the art would have a reasonable expectation of success because Mayandi discloses the crosslinking of ε-polylysine to gelatin at a concentration that reads on the claimed concentration. Daneault discloses that gelatin and hydrolyzed collagen have the same composition and Mayandi discloses that the crosslinking occurs at the molecular level occurs at -NH2 and -C=O moieties. A person of ordinary skill in the art would reasonably expect the same chemistry to occur with both gelatin and hydrolyzed collagen because they have the same composition and therefore an extremely similar number of available -NH2 and -C=O moieties.
Consequently, claim 1 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 2, claim 1 is obvious as described above. Claim 2 recites the case wherein the range of polylysine is 0.05%-25 wt% of the composition. Mayandi discloses a 10% w/w ε-polylysine composition:” A homogeneous gelatin solution (10% w/v) was prepared in 90% TFE containing εPL (10% w/w of gelatin) and dopamine hydrochloride (2% w/w of gelatin) and incubated overnight with gentle stirring. The concentration of εPL was chosen so that the crosslinked mats displayed ≥4 log10 decrease in the viability of bacterial strains after 24 h exposure.” (Mayandi et al., page 16000, col. 2, para. 2).
Consequently, claim 2 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 4, claim 1 is obvious as described above. Claim 4 recites the case wherein the polylysine comprises ε-polylysine. Mayandi discloses a 10% w/w ε-polylysine composition:” A homogeneous gelatin solution (10% w/v) was prepared in 90% TFE containing εPL (10% w/w of gelatin) and dopamine hydrochloride (2% w/w of gelatin) and incubated overnight with gentle stirring. The concentration of εPL was chosen so that the crosslinked mats displayed ≥4 log10 decrease in the viability of bacterial strains after 24 h exposure.” (Mayandi et al., page 16000, col. 2, para. 2). Consequently, claim 4 in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 8, claim 1 is obvious as described above. Claim 8 recites a level of antimicrobial activity. MPEP 2112.01(II) states: “Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.” The obvious composition of claim 1 necessarily possesses the claimed properties. Consequently, claim 8 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 recites the case wherein the composition enhances a natural regeneration process. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.” The obvious composition of claim 1 necessarily possesses the claimed properties. Consequently, claim 9 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Claim 15 recites several forms the composition may exist in. León-López discloses that hydrolyzed collagen, when combined with other biopolymers, may take on the form of foams and films: “It is necessary to combine it with other biopolymers [26,75]. HC presents several advantages compared to native collagen. Some of them consist in higher therapeutic loading, cost-effectiveness and not requiring a multistep extraction procedure, highly digestible and is easily absorbed and distributed in the human body [75,76]. Furthermore, it exhibits lower viscosity in aqueous solution, neutral odor, colorlessness, transparency, emulsification and stabilization, foam forming, film forming, wettability, solubility, dispersibility, powder compressibility, carrier substance and low allergenicity [65,77].” (León-López et al., page 4, para. 2). Consequently, claim 15 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 16, claim 1 is obvious as described above. Mayandi discloses contacting burned tissue with εPL gelatin: “Burns treated with εPL_Gel_pDA displayed early signs of wound contraction and re-epithelialization and better cosmetic outcome in comparison to silver dressings. In clinical practice, the BWAT score is considered decisive as it provides information on wound status and continuity of care for the patients. Instead of considering all possible parameters, wound edge (1, invisible and 5, well defined), granulation tissue (1, intact skin and 5, none), and epithelialization (1, intact surface and 5, <25% wound covered), which best describe the wound status, are compared. The higher the overall score, the more critical is the wound status.” (Mayandi et al., page 15994, col. 2, para. 3).
Mayandi further discloses that bacterial load was reduced: “Together with the microbiology data, these results suggest the presence of critically colonized wounds that warrant antimicrobial treatment. (52) The bacterial populations began to decrease upon treatment with the antimicrobial dressings (Figure7D). For Aquacel Ag treated burns, there was no significant decrease in bacterial populations even after day 32 post-inoculation as the average inoculum remained similar (6.6 ± 0.4 log10) as the initial inoculum. However, three of the five infected burns treated with εPL_Gel_pDA dressings did not contain detectable colonies (>2 log10 decrease from initial inoculum), confirming that the treatment resulted in a substantial decrease in bacterial populations at the wound sites. A similar reduction in bacterial bioburden was observed when the efficacy of εPL_Gel_pDA dressing was compared with untreated burns (Figure S9E). These results demonstrate that the nanofiber dressings decreased the bacterial bioburden while accelerating the wound closure in critically colonized Pseudomonas infections.” (Mayandi et al., page 15999, col. 1, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to treat tissue with the composition of León-López and Mayandi, which comprises polylysine, to achieve the antimicrobial benefits as described by León-López and Mayandi to treat wound such as burns.
A person of ordinary skill in the art would be motivated to employ this method in any situation where the antimicrobial properties of HC and polylysine as described by León-López and Mayandi would be beneficial for target tissue, such as wound/burn recovery.
A person of ordinary skill in the art would have a reasonable expectation of success because Mayandi discloses that the composition successfully assists in healing and improves bacterial load, as described above.
Consequently, claim 16 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. Claim 17 recites the case where the tissue is impaired tissue. Impaired tissue is defined by the specification at para. [0056]: “Examples of tissue defects (e.g., impaired tissue) that can be treated by the hydrolyzed collagen-based compositions described herein include, but are not limited to, surgical incision sites, lesions, fissures, fistulas and diverticula.”
The tissue described above by Mayandi is burned tissue. A person of ordinary skill in the art would reasonably consider this to be impaired tissue. Consequently, claim 17 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 18, claim 16 is obvious as described above. Mayandi discloses the case wherein the polylysine is ε-polylysine: “Burns treated with εPL_Gel_pDA displayed early signs of wound contraction and re-epithelialization and better cosmetic outcome in comparison to silver dressings. In clinical practice, the BWAT score is considered decisive as it provides information on wound status and continuity of care for the patients. Instead of considering all possible parameters, wound edge (1, invisible and 5, well defined), granulation tissue (1, intact skin and 5, none), and epithelialization (1, intact surface and 5, <25% wound covered), which best describe the wound status, are compared. The higher the overall score, the more critical is the wound status.” (Mayandi et al., page 15994, col. 2, para. 3).
Consequently, claim 18 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 19, claim 16 is obvious as described above. Claim 19 recites the case wherein the composition exhibits a certain antimicrobial efficacy. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.” The obvious composition employed by the method of claim 16 necessarily possesses the claimed properties. Consequently, claim 19 is obvious in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Regarding claim 20, claim 16 is obvious as described above. Claim 20 recites the case wherein the composition enhances a natural regeneration process. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.” The obvious composition employed by the method of claim 16 necessarily possesses the claimed properties. Consequently, claim 20 is obvious in view of Mayandi et al. as evidenced by Daneault et al. and rejected.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over León-López et al. (León-López,et al. Molecules 24.22: 4031 (2019)) in view of Mayandi et al. (Mayandi, Venkatesh, et al. ACS applied materials & interfaces 12.14: 15989-16005 (2020)) as evidenced by Daneault et al. (Daneault, et al. Critical Reviews in Food Science and Nutrition 57.9: 1922-1937 (2017)) as applied to claim 1 above, and further in view of Liu et al. (Liu, Fang, et al. "Preparation and antibacterial properties of ε-polylysine-containing gelatin/chitosan nanofiber films." International journal of biological macromolecules 164: 3376-3387.(2020)).
Regarding claim 3, claim 1 is obvious as described above. León-López and Mayandi do not disclose a polylysine wt-% 0.1% to 2%. However, Liu discloses a composition wherein the gelatin to polylysine ratio is 6:0.0625, which results in a wt-% of 0.01%. This composition is able to inhibit the growth of bacteria: “The results of inactivation of six different food pathogens, including E. coli S7, K. pneumoniae B6, S. enteritidis H4, Pseudomonas aeruginosa M5, S. aureus G1, and L. monocytogenes L1 by the prepared nanofiber films are shown in Fig. 8. All the prepared nanofiber films showed effective bactericidal activities to the six foodborne pathogens. The bacterial counts for the six pathogens after treated with the nanofiber films of G/C/P (6:1:0.0625) and G/C/P (6:1:0.125) were significant lower than those samples treated with nanofiber films of G/C (6:1) when the treatment time was up to 120 min (Fig. 8), which indicating that the addition of ε-PL can increase the antibacterial activity of the G/C nanofiber films.” (Liu et al, page 3383, col. 1, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use polylysine wt-% between those of Liu and Mayandi with the composition of León-López and Mayandi to arrive at the claimed invention.
A person of ordinary skill the art would try the range of 0.1%-2% polylysine as routine optimization because this range lies between two values known to be effective in the prior art: 10% and 0.01%.
Liu establishes that the concentration of polylysine influences the bacterial inhibitory effect of a given gelatin composition:
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(Liu et al., page 3383, Fig. 8).
A higher concentration of polylysine is shown to reduce bacterial counts more. Therefore, this is a results effective variable to be optimized.
A person of ordinary skill in the art would have a reasonable expectation of success for a similar reason: the range of 0.1%-2% is bracketed by a lower and higher value that both are effective.
Consequently, claim 3 is obvious over León-López,et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1 above, and further in view of Liu et al. and rejected.
Claims 5, 6, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over León-López et al. (León-López,et al. Molecules 24.22: 4031 (2019)) in view of Mayandi et al. (Mayandi, Venkatesh, et al. ACS applied materials & interfaces 12.14: 15989-16005 (2020)) as evidenced by Daneault et al. (Daneault, et al. Critical Reviews in Food Science and Nutrition 57.9: 1922-1937 (2017)) as applied to claim 1 above, and further in view of Zheng, et al. (Zheng, et al. Bioactive Materials 6.7: 1878-1909 (2021)) and Kim et al. (Kim, et al. Biomacromolecules 19.7: 2483-2495 (2018)).
Regarding claim 5, claim 1 is obvious as described above. León-López and Mayandi do not disclose α-polylysine. However, Zheng et al. discloses that α-polylysine also has antibacterial properties: “PLL-derived polymers, being positively charged under physiological conditions, have been explored as antibacterial agents with promising antibacterial activity. PLLs are frequently conjugated with hydrophobic polypeptides or other hydrophobic blocks to balance the cationic/hydrophobic components for optimized antibacterial activity (Fig. 2). L-Phenylalanine, L-alanine, and L-leucine are representative hydrophobic amino acid residues which are employed to conjugate with PLLs for antibacterial applications.” (Zheng et al., page 1880, col. 2, para. 2).
Furthermore, Kim et al. discloses that α-polylysine and ε-polylysine have the same functional groups available for crosslinking:
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Kim et al. (page 2484, Fig. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute α-polylysine for ε-polylysine as disclosed by Zheng and Kim in the compositions of León-López and Mayandi to arrive at the claimed invention.
A person of ordinary skill in the art would be substituting of one known element for another to obtain predictable results, since both α-polylysine and ε-polylysine are antibacterial (Zheng et al., page 1880, col. 2, para. 2). Furthermore, both have the same available functional group as disclosed by Kim (Kim et al. page 2484, Fig. 1).
These similarities in structure also provide a person of ordinary skill in the art a reasonable expectation of success when making the substitution because both α-polylysine and ε-polylysine are antibacterial (Zheng et al., page 1880, col. 2, para. 2) and both have the same available functional group as disclosed by Kim (Kim et al. page 2484, Fig. 1).
Consequently, claim 5 is obvious over León-López,et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1 above, and further in view of Zheng, et al. and Kim et al. and rejected.
Regarding claim 6, claim 1 is obvious as described above. Claim 6 recites the case wherein the polylysine comprises both α-polylysine and ε-polylysine. As described above, both α-polylysine and ε-polylysine are antibacterial (Zheng et al., page 1880, col. 2, para. 2) and both have the same available functional group as disclosed by Kim (Kim et al. page 2484, Fig. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use a combination of α-polylysine and ε-polylysine in the composition of León-López and Mayandi. This is a case of combining prior art elements according to known methods to yield predictable results because in combination, each element merely performs the same function as it does separately. Furthermore, MPEP 2144.06(I) states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Consequently, claim 6 is obvious over León-López,et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1 above, and further in view of Zheng, et al. and Kim et al. and rejected.
Regarding claim 7, claim 6 is obvious as described above. Claim 7 further recites the case wherein the mixture of α-polylysine and ε-polylysine ranges from 1:5 to 5:1.
MPEP 2144.06(I) states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Furthermore, such a range of ratios could be achieved through routine optimization as described by MPEP 2144.05(II)(A): “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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).”
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use a combination of α-polylysine and ε-polylysine in a range from 1:5 to 5:1 in the composition of León-López and Mayandi. Specifically, the combination range 1:1 is within the disclosed range and it would have been obvious for a person of ordinary skill in the art to try a 1:1 combination and optimize from that starting point as part of routine optimization.
Consequently, claim 7 is obvious over León-López,et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1 above, and further in view of Zheng, et al. and Kim et al. and rejected.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over León-López et al. (León-López,et al. Molecules 24.22: 4031 (2019)) in view of Mayandi et al. (Mayandi, Venkatesh, et al. ACS applied materials & interfaces 12.14: 15989-16005 (2020)) as evidenced by Daneault et al. (Daneault, et al. Critical Reviews in Food Science and Nutrition 57.9: 1922-1937 (2017)) as applied to claim 1, further in view of Chinatangkul et al. (Chinatangkul, et al. International journal of pharmaceutics 562: 258-270 (2019)).
Regarding claim 10, claim 1 is obvious as described above. León-López and Mayandi do not disclose a laurate ester at 0.1%-5% wt-%. However, Chinatangkul the usage of monolaurin, a laurate ester, for antimicrobial purposes:
“Monolaurin (ML) is a monoester form of lauric acid (C12), which is a medium-chain fatty acid found naturally in human breast milk, coconut oil and palm kernel oil (Lieberman et al., 2006). ML is considered non-toxic and Generally Recognized As Safe (GRAS) (Lieberman et al., 2006). In the US, it has been used as a food emulsifier to prevent microbial growth in the manufacture of food products (Nobmann et al., 2009). Regarding previous studies, ML has a broad-spectrum antimicrobial effect against gram-positive bacteria, especially Staphylococcus aureus, which is the most frequent cause of superficial skin infections, and also has antifungal activity against Candida albicans, an opportunistic fungal pathogen normally found on the skin and in mucous membranes, including those of the mouth, pharynx, gastro-intestinal and genito-urinary tracts (Schlievert and Peterson, 2012, Seleem et al., 2016).” (Chinatangkul et al., page 259, col. 1, para. 2).
Chinatangkul also discloses a monolaurin wt-% of 5% in Table 1 for use in wound healing. (Chinatangkul et al., page 259, Table1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to further add monolaurin at a wt-% of 5% as disclosed by Chinatangkul to the composition of León-López and Mayandi to arrive at the claimed invention.
Monolaurin also has antimicrobial effects as discussed above. The composition of León-López and Mayandi also has antimicrobial effects: “The resulting product is commonly called hydrolyzed collagen (HC). It is composed of small peptides with low molecular weight 3–6 KDa [43,44,45,46]. Its solubility and functional activity (antioxidant, antimicrobial) are related to the type and degree of hydrolysis as well as the type of enzyme used in the process.” (León-López, page 9, para. 1).
MPEP 2144.06(I) states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
Furthermore, the Chinatangkul discloses the concentration of 5% wt-%, which reads on the claimed concentration range. Chinatangkul discloses that this concentration of monolaurin is effective in the role of antimicrobial (Chinatangkul et al., page 268, Fig. 9) and therefore a person of ordinary skill in the art would have a reasonable expectation of success.
Consequently, claim 10 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1, further in view of Chinatangkul et al. and rejected.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over León-López et al. (León-López,et al. Molecules 24.22: 4031 (2019)) in view of Mayandi et al. (Mayandi, Venkatesh, et al. ACS applied materials & interfaces 12.14: 15989-16005 (2020)) as evidenced by Daneault et al. (Daneault, et al. Critical Reviews in Food Science and Nutrition 57.9: 1922-1937 (2017)) as applied to claim 1, further in view of Nangare et al. (Nangare, et al. "Pharmaceutical applications of citric acid." Future Journal of Pharmaceutical Sciences 7.1: 54. (2021)).
Regarding claim 11, claim 1 is obvious as described above. León-López and Mayandi do not disclose a chelating agent as claimed in claim 11. However, Nangare discloses citric acid as a chelator: “Additionally, it is also used as a regular ingredient for cosmetic pH-adjustment and as a metallic ion chelator in antioxidant systems.” (Nangare, page 2, col. 1, para. 1). Nangare also discloses that “As per literature, CA is a multifunctional, non-toxic, ready to use, and economical monomer used for pharmaceutical applications.” (Nangare, page 3, col. 1, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the composition of León-López and Mayandi with the citric acid chelator of Nangare to arrive at the claimed invention. A person of ordinary skill in the art would include a metal chelator to sequester harmful metal ions and would use citric acid because it is non-toxic and ready to use as described by Nangare. Consequently, claim 11 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1, further in view of Nangare et al. and rejected.
Claims 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over León-López et al. (León-López, et al. Molecules 24.22: 4031 (2019)) in view of Mayandi et al. (Mayandi, Venkatesh, et al. ACS applied materials & interfaces 12.14: 15989-16005 (2020)) as evidenced by Daneault et al. (Daneault, et al. Critical Reviews in Food Science and Nutrition 57.9: 1922-1937 (2017)) as applied to claim 1, further in view of Maxson et al. (Maxson, et al. Stem cells translational medicine 1.2: 142-149. (2012)).
Regarding claim 12, claim 1 is obvious as described above. León-López and Mayandi do not disclose an anti-inflammatory agent. However, Maxson discloses: “Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC), which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat. In addition to multilineage differentiation capacity, MSCs regulate immune response and inflammation and possess powerful tissue protective and reparative mechanisms, making these cells attractive for treatment of different diseases. The beneficial effect of exogenous MSCs on wound healing was observed in a variety of animal models and in reported clinical cases. Specifically, they have been successfully used to treat chronic wounds and stimulate stalled healing processes.” (Maxson et al, page 142, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the mesenchymal stem cells of Maxson with the composition of León-López and Mayandi to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to make this combination to improve the healing properties of the composition and would have a reasonable expectation of success because Maxson discloses several instances of the usage of mesenchymal stem cells for wound healing (Maxson et al., page 145, Table 1). Furthermore, MPEP 2144.06(I) states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
Consequently, claim 12 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1, further in view of Maxson et al. and rejected.
Regarding claim 13, claim 1 is obvious as described above. León-López and Mayandi do not disclose a stem cell component. However, Maxson discloses: “Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC), which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat. In addition to multilineage differentiation capacity, MSCs regulate immune response and inflammation and possess powerful tissue protective and reparative mechanisms, making these cells attractive for treatment of different diseases. The beneficial effect of exogenous MSCs on wound healing was observed in a variety of animal models and in reported clinical cases. Specifically, they have been successfully used to treat chronic wounds and stimulate stalled healing processes.” (Maxson et al, page 142, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the mesenchymal stem cells of Maxson with the composition of León-López and Mayandi to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to make this combination to improve the healing properties of the composition and would have a reasonable expectation of success because Maxson discloses several instances of the usage of mesenchymal stem cells for wound healing (Maxson et al., page 145, Table 1). The composition of León-López is also used for wound healing. Furthermore, MPEP 2144.06(I) states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
Consequently, claim 13 is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1, further in view of Maxson et al. and rejected.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over León-López et al. (León-López,et al. Molecules 24.22: 4031 (2019)) in view of Mayandi et al. (Mayandi, Venkatesh, et al. ACS applied materials & interfaces 12.14: 15989-16005 (2020)) as applied to claim 1, further in view of Suflet et al. (Suflet, et al. Digest Journal of Nanomaterials and Biostructures 6.2: 653-661. (2011)).
Regarding claim 14, claim 1 is obvious as described above. León-López and Mayandi do not disclose a polysaccharide. However, Suflet discloses that hydrolyzed collagen and polysaccharides can be combined to from useful hollow microcapsules for drug encapsulation: “
These hollow microcapsules obtained from LbL deposition of hydrolyzed collagen and a biodegradable polysaccharide can be used in future studies for encapsulation of active principle for medical and pharmaceutical application.” (Suflet, et al., page 660, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the polysaccharides of Suflet with the composition of León-López and Mayandi to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to make this combination to create the hollow microcapsules as disclosed by Suflet and would have a reasonable expectation of success because Liu shows that this combination successfully produces microcapsules (Suflet et al., page 658, Figure 6). Consequently, claim is obvious over León-López et al. in view of Mayandi et al. as evidenced by Daneault et al. as applied to claim 1, further in view of Suflet et al. and rejected.
Response to Arguments
Applicant's arguments filed 6/17/2026 have been fully considered but they are not persuasive.
Claims 1, 2, 4, 8, 9, and 15-20:
Regarding Mayandi and polylysine, Applicant asserts that: “In analyzing the antimicrobial activity, Mayandi relates to the polylysine-gelatin- polydopamine crosslinked dressing at 2 mg/mL polylysine retaining antimicrobial activity of 2 - 4 log kill of planktonic P. aeruginosa, which is substantially less than polylysine alone at 2 mg/mL providing 6 log kill of the more robust biofilm P. aeruginosa. See id. at 15990, Fig 1 D, 15994, Table 1. In other words, the incorporation of polylysine into a crosslinked complex reduced the antimicrobial activity of the resulting composition.
Based on Mayandi, in which the incorporation of polylysine into a crosslinked complex results in the depletion of polylysine's antimicrobial activity in the crosslinked complex of gelatin and polydopamine, Mayandi teaches away from incorporating polylysine in a potentially even more neutralizing environment, such that of hydrolyzed collagen such that a person of ordinary skill in the art, at the time of the effective filing date of the present application, would have found no teaching or suggestion to have found it obvious to combine Leon-Lopez and Mayandi to arrive at the instantly-claimed subject matter. Therefore, the instant claims are nonobvious and allowable over Leon-Lopez and Mayandi.” (Applicant Reply, page 7, para. 4).
This assertion is addressed by MPEP 2145(X)(D)(1): “A prior art reference that "teaches away" from the claimed invention is a significant factor to be considered in determining obviousness. However, "the nature of the teaching is highly relevant and must be weighed in substance. 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, 553, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)”
The composition of Mayandi may possess less antimicrobial activity than pure polylysine, but this does not constitute a teaching away because the composition still has antimicrobial activity. Furthermore, a person of ordinary skill in the art may knowingly accept the reduced in activity in exchange for having the polylysine in a deliverable form, in this case gelatin. This situation constitutes a tradeoff, which is not a teaching away.
Regarding gelatin and hydrolyzed collagen, Applicant asserts: “Based on the foregoing, because a person of ordinary skill in the art, in seeking to provide a composition having good antimicrobial activity, would not have sought to incorporate polylysine in a hydrolyzed collagen environment in which polylysine would be expected to have a reduction in antimicrobial as in Mayandi with the scaffold of Leon-L6pez and have found it obvious to arrive at the presently-claimed subject matter. Further, collagen, gelatin, and hydrolyzed collagen, despite being composed of amino acids, each have distinct chemical and physical properties such that there would be no teaching or suggestion to utilize one over the other. Therefore, the instant claims are nonobvious and allowable over Leon-Lopez and Mayandi.
Accordingly, Applicant respectfully requests that the rejection based on Leon-Lopez and Mayandi be withdrawn.” (Applicant Reply, page 10, para. 2).
Examiner acknowledges that such a phenomenon is disclosed and studied by the prior art by Hyldgaard, et al. (Hyldgaard, Applied and environmental microbiology 80.24: 7758-7770 (2014)).
Hyldgaard discloses a mutant JW5917-1 of E. Coli which constitutively expresses a negatively charged acid molecule: “In addition to the effects from changes to the LPS structure, we also found an increased tolerance to ε-PL in the ΔrscC mutant, which overexpresses the capsular exopolysaccharide colanic acid (Table 1). Colanic acid helps to regulate the three-dimensional structure of E. coli biofilms (41) and functions as a protective barrier (42). We therefore propose that the colanic acid chelates ε-PL and thereby increases the tolerance of the rscC mutant by preventing or delaying its access to the inner and outer membranes.” (Hyldgaard et al., page 7764, col. 2, para. 1).
Referring to Table 1 of Hyldgaard, the efficacy of polylysine is only reduced by a factor of approximately two-fold by this phenomenon:
PNG
media_image4.png
153
1266
media_image4.png
Greyscale
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52
1209
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Greyscale
(Hyldgaard, et al., page 7760, Table 1).
Hyldgaard also discloses that cationic media presents a more severe issue for the mechanism of polylysine: “Due to the electrostatic nature of the interaction, as well as differences in the ability of ε-PL to access the membrane, the effect of ε-PL can be competitively inhibited by cations in the surrounding liquid.” (Hyldgaard et al., page 7768, col. 1, para. 2).
MPEP 2145(X)(D)(1) is again relevant: “A prior art reference that "teaches away" from the claimed invention is a significant factor to be considered in determining obviousness. However, "the nature of the teaching is highly relevant and must be weighed in substance. 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, 553, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)”
In the instant case, such a relatively minor reduction in polylysine efficiency cannot be considered a proper teaching away.
Furthermore, because no such teaching away exists, and because both polylysine and hydrolyzed collagen are antimicrobial separately, MPEP 2144.06(I) still holds: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
Regarding claim 3, Liu is invoked to establish an effective polylysine concentration of 0.01 wt% which creates a range of 0.01 wt% and 10 wt% when taken with Mayandi above. This establishes the claimed concentration as prima facie obvious by MPEP 2144.05(I): “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).”
Liu is not invoked to disclosed hydrolyzed collagen, as that concept has already been established in the rejection of claim 1. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding claims 5-7, the interaction of polylysine with negatively-charged molecules is addressed experimentally above in Hyldgaard. The mere presence of negatively charged molecules is not a teaching away from the usage of polylysine without further experimental data submitted as evidence.
Regarding the remaining claims 10-14, the rejections of these claims do not need to overcome deficiencies of claim 1. The rejection of claim 1 is proper as described above and therefore the rejections of claims 10-14 are also proper as currently presented.
Conclusion
No claim is allowed.
Claims 1-20 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654
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