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 .
Claim Status
Claims 1-20, 22-31 are cancelled.
Claim 42 is new.
Claims 21 and 32-42 are pending.
Claims 36, 38 and 39 are withdrawn.
Claims 21, 32-35, 37 and 40-42 are presented for examination. Support for amended claim 1 is found in the specification on page 22, lines 12-15. In new claim 42, diethylamino hydroxybenzoyl hexyl benzoate is known to the artisan as Uvinul A plus. (Specification page 16, lines 29-30.) Applicant’s amendment has necessitated modification of the existing rejection to address the newly presented limitation(s). Accordingly, this Action is FINAL.
Withdrawn rejections
Applicant's amendments and arguments filed 6/16/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn. Claims 21, 32-35, 37 and 40-41 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Applicant has amended the claims.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 21, 32-35, 37 and 40-42 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al. (US20180256480) and Panyam et al. (WO2008091465) and Thermo Fisher Scientific ([online] retrieved on 10/31/24 from: https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/polyethylene-glycol-peg-pegylation-proteins.html; 14 pages.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims a set of particles comprising at least one bioadhesive particle as described in claim 21.
Claim interpretation: B comprises: 1) poly(ethylene glycol); or 2) -[Y-(CH2)q]k-(O-CH2-CH2)p- (II); when k is 0 and p is 1, then [Y-(CH2)q] would not be present and B is a repeating chain of –(O-CH2-CH2).
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medical/pharmaceutical drug delivery research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from drug delivery systems and techniques and pharmaceutical chemistry— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 21, 32 and 42, Deng et al. teach a core-shell structure particles that adhere to tissue, cells or extracellular materials, hence bioadhesive particles, and topical sunblock compositions (Abstract) comprising a core of PLA (poly(lactic acid) and copolymers thereof poly(lactic acid-co-glycolic acid) (PLGA) and a functionalized polymer with functional groups (Claims 1-3; [0071, 0073, 0223-0225]), (component A) where the functionalized polymers can be polyglycerols (Claim 5), which have hydroxyl groups, and the one or more reactive functional groups can be aldehydes, amines, O-substituted oximes and combinations thereof (Claim 6) and sunblock/sunscreen agents including UV filters are encapsulated (Claims 8-11; [0109]). In claim 11, Deng et al. name UV-filters: “selected from the group consisting of zinc oxide (ZnO), titanium dioxide (TiO2), avobenzone, tinosorb S, mexoryl SX, mexoryl XL, helioplex, octinoxate, octocrylene, oxybenzone, octisalate, homosalate, uvinul T 150, cinoxate, aminobenzoic acid, padimate O, ensulizole, dioxybenzone, meradimate, sulisobenzone, trolamine salicylate, enzacamene, bisdisulizole di sodium, uvinul A Plus, uvasorb HEB, parsol SLX, amiloxate, p-aminobenzoic acid (PABA), phenylbenzimidazole sulfonic acid, cinoxate, menthyl anthranilate, sulisobenzone, parsol compounds, tinosorb compounds, heliopan compounds, and combinations thereof.” As noted above, Uvinul A Plus is diethylamino hydroxybenzoyl hexyl benzoate. In Example 5, Deng et al. teach synthesis of a set of particles and report obtaining 100% by weight of the particles containing an organic compound used in sunscreens (Example 5, [0323-0327]), which is within the scope of at least 20% by weight. So, Deng et al. teach a polymer core of the elected species and there is at least 1 functional group C, so m ≥ 1, and X is a UV-filter claimed where 100% of the particles are the bioadhesive particles. The particles of Deng et al. are made of the elected species and therefore are implicitly bioadhesive. Deng et al. even state that the particles can adhere to the skin (Claim 1; [0098]). Deng et al. also teach that the particles can release molecules to be encapsulated or attached [0071, 0098, 0108].
Regarding claims 21 and 32, Deng et al. teach embodiments with the linear linker PEG (component B) [0032, 0071, 0158-0160, 0280-0282, 0285], so n = 1. Thus, “B” comprises at least one residue of poly(ethylene glycol). Deng teach employing PEG5000 [0266], thus p = 1 and m is between 1 and 1025.
Regarding claims 21 and 32, the linear linker PEG has a hydroxyl functional group C and can be further functionalized with amines, hydrazines and thiols [0159-0160, 0266] and maleimides, a type of amine (component C), as reactive coupling groups [0064]. Deng et al. also suggest that coupling could be done with streptavidin and biotin [0118].
Regarding claims 33-35 and 40, Deng et al. teach formulating with other excipients [0132] and in the form of a topical formulation (Claim 22; [0185-0187]) also for use in hair treatment products (Claim 12), such as hair coloring/dye [0027, 0236-0238], and wound dressings (Claim 15; [0026, 0239-0244]) and to add skin soothing emollients [0195] and skin repair/anti-aging products [0234-0235], which would provide care to the skin with a composition comprising a set of particles. Deng et al. also teach adding anti-aging components (Claim 13) to the topical composition for application to the skin (Claims 1 and 7; claim 23), thus making it a cosmetic composition and a composition for skin care, hair care, etc., and the wound dressing is a medical device.
Regarding claim 37, the spray, liquid or powder formulations (Claim 12) of Deng et al. implicitly have a “washing composition” added as defined by the instant specification (Page 3, lines 11-16). Optional components are not required.
Regarding claim 41, Deng et al. teach that the particles are designed to release molecules to be encapsulated or attached covalently or non-covalently [0071, 0098, 0107-0108] where in preferred embodiments the molecules to be attached are particles blocking or filtering UV radiation [0109].
Regarding claims 21 and 32, Panyam et al. disclose a method that employs a composition of nanoparticles, thus reading on a set of particles, comprising at least one polymer and at least one therapeutic agent joined thereto (Claim 1) where the polymer is poly(lactic acid), poly(lactide), poly(glycolic acid), (poly(lactic-co-glycolic acid) (Claims 3-4), the therapeutic agent can be a polysaccharide, a peptide, a polypeptide, a nucleic acid, a vitamin, a mineral, a vaccine, a cytokine, an apoptotic agent, a cytotoxic agent, and a pharmaceutical drug (Claims 5-6), which is encapsulated (Page 39, lines 10-12) and the nanoparticle can further comprise a functional group joined thereto that is alkane, alkene, alkyne, amide, amine, imide, phosphine, phosphodiester, phosphonic acid, phosphate, sulfide, imidazole and oxazole (Claim 8) and a specific example with maleimide (Page 43, Example 8 and see page 24, line 38 through page 25, line 6 for functional groups within the scope of the claims), which means at least 1 functional group.
Regarding claims 21 and 32 where n = 1 such that linear linker B “polyalkylene glycols” is present, Panyam et al. disclose nanoparticles comprising PLGA with a diblock copolymer polylactide-polyethylene glycol with terminal maleimide functional group and c(RGD) peptide (Example 8) and a diblock copolymer polylactide-polyethylene glycol with terminal amine functional group and FLUORESCEIN ISOTHIOCYANATE (Example 9). Polyethylene glycol has a repeat unit of (O-CH2-CH2) with p = 1, thus reading on at least the conditions of: A comprises at least one residue of poly(lactic acid), B comprises at least one residue of poly(ethylene glycol), C is maleimide or a derivative thereof, and m is comprised between 1 and 1025.
Regarding claims 21 and 32, Thermo Fisher Scientific teaches commercially available polyethylene glycols with 2-24 PEG units that also have a maleimide group at one end (bottom of page 5 into page 6; Bifunctional pegylated crosslinkers) as well as amine to sulfhydryl crosslinkers with PEG spacer arms of 2-24 ethylene glycol units (Page 6).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Deng et al. is that Deng et al. do not expressly teach an embodiment where n is 1 and C represents a maleimide group and the UV-filter is attached to the particle or adding instructions. This deficiency in Deng et al. is cured by the teachings of Panyam et al. and Thermo Fisher Scientific.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate or attach any of the UV-filters claimed to the particle of Deng et al. where n is 1 and C represents a maleimide group and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because Deng et al. teach and suggest encapsulating or attaching a UV-filters and having the linear linker PEG has a hydroxyl functional group C and can be further functionalized with amines such as maleimides and provide the methods for attaching molecules with various functional groups. It is simple selection of a maleimide reactive group, as suggested by Deng et al., where Panhyam et al. teaches using PLA-PEG(maleimide) or PLA-PEG(NH2) (Page 41, line 15-16; Example 8) and Thermo Fisher Scientific teaches commercially available polyethylene glycols with 2-24 PEG units that also have a maleimide group at one end (bottom of page 5 into page 6; Bifunctional pegylated crosslinkers). It is then obvious to employ a maleimide reactive groups in the topical formulation particles of Deng et al. as Panhyam et al. provide examples of use and Thermo Fisher Scientific provides a commercial source to obtain the maleimides, with a reasonable expectation of success. Moreover, adding instructions to a kit on how to apply the product is obvious to the artisan. One would do so to ensure that the product is properly applied by the lay person and not improperly used. One would do so with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined 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 combined references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments filed 1/156/16/26 have been carefully considered but are not persuasive.
On page 6 of remarks, Applicant asserts that: “The particles of Deng are not made of the combination of elements set forth in claim 21 and are, therefore, not implicitly bioadhesive. As acknowledged by the Office Action, Deng does not teach n is 1, C represents a maleimide group and the UV-filter is attached to the particle…Thus, Deng's particles are structurally distinct from the claimed bioadhesive particles, and are not implicitly bioadhesive.” Respectfully, the Examiner has a different perspective. First, claim 21 recites: “where said bioadhesive particle encapsulates or is attached to at least one active agent X”. As discussed above, Deng et al. teach that the particles are designed to release molecules to be encapsulated or attached covalently or non-covalently [0071, 0098, 0107-0108] where in preferred embodiments the molecules to be attached are particles blocking or filtering UV radiation [0109]. Secondly, Deng et al. teach a core-shell structure particles that adhere to tissue, cells or extracellular materials. Since tissue, cells or extracellular materials are biological substrates, then that makes the particles of Deng et al. bioadhesive.
On pages 6-7 of remarks, Applicant asserts that all of Deng’s nanoparticles that are disclosed as bioadhesive are hyperbranched polymers such as polyglycerol that have been chemically modified and does not disclose PEG as bioadhesive. However, Deng et al. expressly teach attaching PEG to the hyperbranched polymer (Examiner added emphasis): “The HP coating can be modified by attaching PEG to the surface of the coating. For example, RPG-coated particles can be modified by covalently attaching PEG to the surface.” [0159]. That means that the PEG is attached to the hyperbranched polymer coating. While the Examiner is aware that PEG with a functional group or linker can form a bond with an aldehyde on PLA-HPGALD (PLA-HPGALD-PEG) and reverse the bioadhesive state of PLA-HPGALD to stealth state, that bond is labile and once cleaved the bioadhesive state is returned [0160]. Furthermore, the rejection is over formula (I):
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70
434
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Greyscale
which requires modification of component B with a maleimide group C. The question raised is if it obvious to modify the other hydroxyl group of PEG with maleimide to make it bioadhesive. The Examiner acknowledges the fact that Deng et al. prefer the hyperbranched nature of the polyglycerols, which allows for a much higher density of hydroxyl groups, reactive functional groups, and/or targeting moieties than obtained with linear polyethylene glycol [0099]. But that does not amount to a teaching away from employing PEG because Deng et al. do not criticize, discredit or otherwise discourage employment of the alternative hydroxyl moiety bearing PEG. See MPEP 2141.02[R-5] VI. The ordinary artisan with the reference in hand readily understands that the hydroxyl moiety of PEG is available for modification with maleimide to produce a bioadhesive particle of PLA-PEG-maleimide structure. So, while the hyperbranched polyglycerols appears preferable to Deng et al. over the linear polyethylene glycols, a known or obvious invention does not become patentable simply because it has been described as somewhat inferior to some alternative for the same use. In re Gurley, 27 F.3d 551, 554 (Fed. Cir. 1994) (MPEP 2123(II)). Applicant’s arguments are not persuasive.
Applicant asserts that: “Deng's particles are structurally distinct from the claimed bioadhesive particles, and are not implicitly bioadhesive.” However, modification with maleimide imparts bioadhesiveness. The Examiner points out that Deng is not applied in a vacuum but is combined with Panyam et al. and Thermo Fisher Scientific. It is impermissible to attack references singly when the Examiner relies upon the combined teachings of the references, nor may they attack a reference for not teaching a limitation of the claim when the Examiner has explicitly relied upon another reference as teaching that limitation. See In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000).
On page 7 of remarks, Applicant argues that Deng fails to disclose nanoparticles containing PEG as bioadhesives and Deng does not teach or suggest a PLA-PEG bioadhesive as alleged by the Office Action. Respectfully, the Examiner does not agree because Deng et al. expressly teach several things. Deng et al. teaches that: “The core can be formed of copolymers including amphiphilic copolymers such as PLGA-PEG” [0071]. See also Table 1 teaching PLA-PEG nanoparticles of 103.3 nm diameter (Page 22, top right column) and claim 3 teaching: wherein the hydrophobic polymer is selected from the group consisting of poly(lactic acid), poly(glycolic acid), and copolymers thereof.” Deng et al. expressly teach components A and B of formula I in claim 21. Deng et al. also suggest tuning (optimization) of the surface: “the surface properties can be tuned to provide stealth particles, i.e., particles that are not cleared by the MPS due to the presence of the hydroxyl groups; adhesive (sticky) particles, i.e., particles that adhere to the surface of tissues” [0098]. See also [0321]: “The density of the aldehydes on NPs can be controlled thereby providing tunability in the behavior of the PLA-HPGALD NPs for local delivery”. Moreover, as asserted above, Deng et al. expressly teach (Examiner added emphasis): “The HP coating can be modified by attaching PEG to the surface of the coating. For example, RPG-coated particles can be modified by covalently attaching PEG to the surface.” [0159]. That means that the PEG is attached to the hyperbranched polymer coating. The surface properties are adjusted based on the chemistry of the hydroxyl groups by introduction of reactive functional groups [0098] such as maleimides, where: “The selection of reactive coupling groups is within the ability of the skilled artisan.” [0064]. Furthermore, Deng et al. teach sunscreen formulation where the active agent penetrates the skin effectively, while in other embodiments skin penetration is delayed or reduced such that the active agents are at or near the surface of the skin [0219]. Taken as a whole, the ordinary artisan can adjust/tune/optimize/control the surface chemistry of the particles to delay or reduce or maintain active agents at or near the surface of the skin, where it is understood that bioadhesiveness is directly proportional to the number of reactive groups present. (As noted above, Deng et al. teach: “The density of the aldehydes on NPs can be controlled thereby providing tunability in the behavior of the PLA-HPGALD NPs for local delivery” [0321].) Consequently, it is obvious to modify the hydroxyl group on PEG with a reactive group such as maleimide to impart a tunable bioadhesive property.
The Examiner will simplify the Examiner’s position:
Deng et al. expressly teach PLA-PEG and PLA-HPGALD-PEG where PEG provides a hydroxyl group.
Deng et al. expressly teach modification of hydroxyl groups with reactive groups, such as aldehyde and conventionally known maleimide, to impart tunable bioadhesiveness.
PLA-PEG and PLA-HPGALD-PEG have a hydroxyl group.
It is then obvious to modify the hydroxyl group of PLA-PEG and PLA-HPGALD-PEG with maleimide to impart desirable bioadhesiveness1.
On pages 7- 9 of remarks, Applicant argues that: “The Office Action merely alleges that the individual elements of the claimed invention were each known in the prior art… The Office Action has not provided a reason why one skilled in the art would have been motivated to combine Paynam and Thermo Fisher with Deng”; and “Deng teaches bioadhesive particles while neither Paynam nor Thermo Fisher even mention adhesion, let alone bioadhesion.” Respectfully, the Examiner does not agree because Deng et al. expressly teach maleimides as a reactive coupling group and: “The selection of reactive coupling groups is within the ability of the skilled artisan.” [0064] The secondary references teach and suggest conventional maleimides for use. Paynam and Thermo Fisher are not relied upon for teaching bioadhesive particles but rather as characterized by the Examiner in the rejection. See In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000) above. Thus, there is an express reason provided by Deng et al. for the ordinary artisan to look for what types of maleimides are taught in the art for the same purpose. The relevant case law states: “The combination of familiar elements [or steps] according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). However, please note that: “One way for a patent applicant to rebut a prima facie case of obviousness is to make a showing of ‘unexpected results,’ i.e., to show that the claimed invention exhibits some superior property or advantage that a person of ordinary skill in the relevant art would have found surprising or unexpected.” In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995). At this time, Applicant has not argued unexpected results and Applicant has failed to produce any evidence of unexpected results from C being a maleimide. The Examiner reviewed Example 13 “Bioadhesion Tests” and the data in Table 1, which demonstrates bioadhesion. However, bioadhesion is an expected result. Consequently, it appears that C as a maleimide or derivative thereof is obvious over the combined references.
On page 9 of remarks, Applicant argues that: “Paynam's[sic] cell targeting nanoparticles for intracellular drug delivery are designed to achieve the exact opposite of what Deng's goals are-bioadhesion of UV filter containing particles to the skin surface without penetration into the skin or skin cells.” And: “the teachings of Paynam[sic] undermine the very reason being proffered by the Office Action why a person of ordinary skill would have combined their teachings”. Respectfully, the Examiner does not agree. Panyam et al. is relied upon as applied in the rejection where Panyam et al. specifically teach PLA-PEG-(maleimide), thereby indicating a reasonable expectation of success in producing PLA-PEG-maleimide and/or PLA-HPGALD-PEG-maleimide from the teachings of Deng et al., which is bioadhesive. Thus, Panyam does not undermine or render Deng et al. unsatisfactory for its intended purpose at all. Applicant’s arguments are not persuasive.
Respectfully, Applicant’s arguments have been carefully considered but are not persuasive.
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 ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 It is well-known in this art that polymers functionalized with maleimide groups exhibit excellent mucoadhesive properties. See page 84, left column 3rd paragraph in: Kaldybekov et al. (Mucoadhesive maleimide-functionalised liposomes for drug delivery to urinary bladder. European Journal of Pharmaceutical Sciences Volume 111, 1 January 2018, Pages 83-90).
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