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 .
Claims Status
Claims 6-17 are cancelled.
Claims 1-5 and 18-32 are pending and presented for examination on the merits.
Priority
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The foreign priority documents are not in English. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/3/25 and 4/15/26 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3 and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KR102254093B1; English language translation provided by the Examiner.
Regarding claims 1 and 2, KR102254093B1 disclose compositions of bilirubin derivative and a metal nanoparticles (Abstract) where the bilirubin is conjugated to a hydrophilic molecule is polyethylene glycol (PEG) having an amine group, thus a derivative of PEG, conjugated to the bilirubin and the PEG has an average MW of 200-20000 Da (Claims). KR102254093B1 exemplify a PEG20001 in Formula 2 shown below (Examples 1 and 2 Page 8):
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See MPEP 2131.03(I): A SPECIFIC EXAMPLE IN THE PRIOR ART WHICH IS WITHIN A CLAIMED RANGE ANTICIPATES THE RANGE
"[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
Regarding claims 18 and 19, KR102254093B1 disclose a complex of bilirubin-PEG metal ionic coordination complex, which is a salt and that salt is pharmaceutically and cosmetically acceptable, because it is used on people for diagnosis (Claims).
Regarding claims 3 and 20, KR102254093B1 disclose dissolving the bilirubin conjugated with PEG in water so prepare self-assembled bilirubin particles (Page 8, 1.2), which would be nanoparticulate2 and creates an aqueous cosmetic composition. The term “cosmetic” is merely an intended use of the composition and imparts no structural information into the claim.
Claim(s) 1-5 and 18-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jon et al. (US20170028076).
Regarding claims 1-5, 18-20, 23-26, Jon et al. disclose a bilirubin nanoparticle formed by the self-assembly of bilirubin and a composite comprising a hydrophilic polymer that exhibits antioxidant, antiangiogenic, anticancer, and anti-inflammatory activities (Abstract; Figure 3) where Jon et al. disclose synthesis with mPEG2000-NH2 , methoxy polyethylene glycol 2000 having terminal amine group [0166] which had a particle size of 100 nm in phosphate buffer ([0168-0171]; see also Figures 5 and 8), where it is understood that phosphate buffer is made up of a dihydrogen phosphate ion, which acts as a weak acid, and a monohydrogen phosphate ion, which acts as a weak base, which the instant specification teaches as non-toxic salts [096], and the particles size is within the claimed range of 1-5000 nm and thus makes pharmaceutical and cosmetic acceptable salt compositions. See MPEP 2131.03(I).
Regarding claims 21-25, Jon et al. teach that the pharmaceutical composition is for preventing or treating an inflammatory disease (Claims 19-20) and a method of treating inflammation colitis by administration of the bilirubin nanoparticles (BRNVs) [0199-0202] with the composition disclosed above.
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 1-5 and 18-32 are rejected under 35 U.S.C. 103 as being unpatentable over Jon et al. (US20170028076) as applied to claims 1-5 and 18-25 above, and KR102254093B1 and Keum et al. (Journal of Controlled Release 2020;325:359-369; of record) and Weidner (US20060222671) and D’souza et al. (EXPERT OPINION ON DRUG DELIVERY, 2016 VOL. 13, NO. 9, 1257–1275).
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; for example:
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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).
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)
It is well settled that “a disclosure that anticipates under § 102 also renders the claim invalid under §103, for anticipation is the epitome of obviousness. See MPEP 1207.03(a)(II) states: “"lack of novelty is the epitome of obviousness." May, 574 F.2d at 1089, 197 USPQ at 607 (citing In re Pearson, 494 F.2d 1399, 1402, 181 USPQ 641, 644 (CCPA 1974))”. Accordingly, the claims rejected under §102 above are also invalid under §103.
The reference of Jon et al. is discussed in detail above and that discussion is incorporated by reference.
Further regarding claims 4 and 24, Jon et al. teach nanoparticle sizes of 1-5000 nm or 50-1000 nm or 50-500 nm [0023].
Further regarding claims 5 and 25, Jon et al. teach the hydrophilic polymer is a polyethylene glycol or a derivative thereof. Examples of the polyethylene glycol
derivative may include methoxy polyethylene glycol (PEG), succinimide of PEG propionic acid, succinimide of PEG butanoic acid, branched PEG-NHS, PEG succinimidyl succinate, succinimide of carboxymethylated PEG, benzotriazole
carbonate of PEG, PEG-glycidyl ether, PEG-oxycarbonylimidazole, PEG nitrophenyl carbonates, PEG-aldehyde, PEG succinimidyl carboxymethyl ester, and PEG succinimidyl ester [0040].
Further regarding claims 18-20, Jon et al. teach that: “The pharmaceutical composition of the present invention is formulated using a pharmaceutically acceptable
carrier and/or excipient, according to the method that is easily conducted by a person having ordinary skills in the art to which the present invention pertains [0069]. The claimed cosmetic composition is merely semantics and intended use of the composition without more.
Regarding claims 21-22 and 29-30, Jon et al. teach that the pharmaceutical composition is for preventing or treating an inflammatory disease (Claims 19-20) and “At the inflammation site, the nanoparticles can exhibit an anti-inflammatory activity by scavenging an abnormal level of reactive oxygen species.” [0053] Jon et al. also teach a method of treating inflammation colitis by administration of the bilirubin nanoparticles (BRNVs) [0199-0202], which is a bilirubin nanoparticle formed by the self-assembly of bilirubin and a composite comprising a hydrophilic polymer that exhibits antioxidant, antiangiogenic, anticancer, and anti-inflammatory activities (Abstract; Figure 3; [0167-0169]) where Jon et al. disclose synthesis with mPEG2000-NH2 , methoxy polyethylene glycol 2000 having terminal amine group [0166] which had a particle size of 100 nm in phosphate buffer ([0168-0171]; see also Figures 5 and 8), where it is understood that phosphate buffer is made up of a dihydrogen phosphate ion, which acts as a weak acid, and a monohydrogen phosphate ion, which acts as a weak base, which the instant specification teach as non-toxic salts [096], and the particles size is within the claimed range of 1-5000 nm and thus makes pharmaceutical and cosmetic acceptable salt compositions.
Regarding claims 26-32, Jon et al. teach: “Examples of the inflammatory diseases, to which the present invention can be applied, may include inflammatory bowel disease, atopic dermatitis, edema, dermatitis, allergies, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, atherosclerosis, pharyngolaryngitis, tonsillitis, pneumonia, gastric ulcers, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, Periarthritis of shoulde, tendinitis, tenosynovitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome, and multiple sclerosis [0055]. Thus, treatment of the skin inflammation diseases, such as atopic dermatitis, which are implicitly caused by increased oxidative stress, naturally ameliorates skin inflammation, moisturizes the skin and resorts skin barrier function.
Regarding claims 1, 21, 26-32, Keum et al. teach bilirubin nanoparticles as a novel nanomedicine for ameliorating psoriasis-like skin inflammation through topical treatment and suggest that their use could be further expanded to treat other chronic skin inflammation diseases, including atopic dermatitis (Abstract). Keum et al. use PEG2000 bilirubin (Figure 1; page 360 2.2. Synthesis of PEG-BR and characterization of BRNPs). Keum et al. report that they “validated the potential of BRNPs as a therapeutic nanomedicine for topical treatment of psoriasis. BRNPs readily infiltrated the disrupted outer cornified skin barrier and were readily taken up by keratinocytes, where they efficiently downregulated the accumulation of intracellular ROS. BRNP-mediated attenuation of ROS-induced oxidative stress within keratinocytes subsequently reduced the production of pro-inflammatory cytokines and autoantigens, thereby inhibiting the activation and maturation of APCs.” (Page 367, 4. Conclusions).
Regarding claims 2 and 22, KR102254093B1 disclose compositions of bilirubin derivative and a metal nanoparticles (Abstract) where the bilirubin is conjugated to a hydrophilic molecule is polyethylene glycol (PEG) having an amine group, thus a derivative of PEG, conjugated to the bilirubin and the PEG has an average MW of 200-20000 Da (Claims).
Regarding claims 26-27, Weidner teaches dermatological disease include acne vulgaris, adult eczema, alopecia, allergic contact dermatitis, allergic dermatitis, allergic contact eczema, asteatotic eczema, atopic eczema, hand eczema, atopic dermatitis, carcinomas, childhood eczema, chronic dermatitis of hands or feet, contact dermatitis, contact eczema, discoid eczema, insect bite inflammation, drug-induced skin reactions, dermatitis herpetiformis, discoid lupus erythematosus, eczema, epidermolysis bullosa, erythroderma, erythema nodosum, erythema multiforme, hand eczema, hand and foot dermatitis, ichthyosis vulgaris, infantile eczema, keratoconus, keratosis pilaris lichen simplex chronicus, lichen planus, nummular dermatitis, melanomas, over-treatment dermatitis, pemphigus, pemphigoid, photodermatoses, pityriasis rosea, pyoderma gangrenosum, pompholyx, psoriasis, prurigo nodularis, rosacea, scabies, seborrheic dermatitis, seborrhea, scleroderma, Sjogren's Disease, stasis dermatitis, subacute cutaneous lupus erythematosus, sunburn, cutaneous manifestations of systemic lupus erythematosus, vitiligo and urticaria. [0242].
Regarding claims 2, 5, 22 and 25, D’souza et al. provide a review on PEG and teach in Figure 1 numerous PEG derivatives and in Table 1 including PEG400, PEG600, PEG1000, PEG1500 and PEG2000 (Page 1259) where “PEG follows two nomenclature systems – (a) CAS and (b) Cosmetics, Toiletry and Fragrance Association (CTFA)/International Nomenclature Cosmetic Ingredient (INCI). PEG used in cosmetics are nomenclatured by CTFA system. The suffix number to PEG in CFTA/INCI system represents the average number of ethylene glycol units in PEG. If the number is suffixed by ‘M’, the letter indicates 1000. For instance, PEG-25 M indicates PEG with an average of 25,000 ethylene glycol units.[6] Table 1 enlists wide range of PEG derivatives used in pharmaceutical applications.” (Page 1258, right column).
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)
1. The difference between the instant application and Jon et al. is that Jon et al. do not expressly teach a solvate of the bilirubin compound, all the claimed chain lengths of the PEG or all of the claimed inflammatory diseases. This deficiency in Jon et al. is cured by the teachings of KR102254093B1, D’souza et al., Weidner and Keum et al.
1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make a solvate of the bilirubin compound taught by Jon et al. with any of the claimed PEG chain lengths and administer it in methods of treating all of the claimed inflammatory conditions, as suggested by KR102254093B1, D’souza et al., Weidner and Keum et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. First of all, solvates are obvious because Jon et al. teach dissolving the complex in water where solvation naturally occurs. Secondly, while Jon et al. only appear to teach PEG2000, Jon et al. is not limited to any particular PEG chain length and the art of KR102254093B1 provides a MW range for PEG and D’souza et al. teach numerous common and conventional PEGs for use including those within the MW range of KR102254093B1. Consequently, it is merely judicious selection of known PEG MW sizes to have a chain length of 10, 11, 15, 23, 25 or 47 with a reasonable expectation of success. Thirdly, Jon et al. do not teach all the claimed skin diseases but do name numerous diseases that are claimed. The art of Weidner renders obvious other claimed skin diseases and the ordinary artisan in this art would readily understand that any skin condition that would benefit from the scavenging of reactive oxygen species would also benefit from the method of Jon et al. Keum et al. provide a reasonable expectation of success in so doing. Consequently, all of the claimed subject matter is obvious over the combined references. The test for obviousness is "what the combined teachings of the references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 4I3, 425 (CCPA I98I) (MPEP 2145(III)).
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.
Conclusion
No claims are allowed.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 Given the repeat unit of PEG (-CH2-CH2-O-) is 44 g/mol, then PEG2000 has about 47 repeat units.
2 The inventors of KR102254093B1 state: “The present inventors have developed bilirubin nanoparticles composed of a complex of bilirubin and a hydrophilic polymer” (Page 2, Description).
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