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 .
Restriction/Election
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-9, drawn to a conjugate or a particle comprising a conjugate wherein the conjugate comprises bilirubin linked to chitosan.
Group II, claims 10-20, drawn to a method of treating an inflammatory disease.
This application contains claims directed to more than one species of the generic invention in group II. These species are deemed to lack unity of invention because they are not so linked as to form a single general inventive concept under PCT Rule 13.1.
The species are as follows:
Methods of treating a specific inflammatory disease as disclosed in claims 12-14 comprising administering a pharmaceutically acceptable carrier in combination with a conjugate, particles comprising the conjugate, or a mixture of the conjugate and particles comprising the conjugate, wherein the conjugate comprises bilirubin linked to chitosan
Applicant is required, in reply to this action, to elect a single species to which the claims shall be restricted if no generic claim is finally held to be allowable. The reply must also identify the claims readable on the elected species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered non-responsive unless accompanied by an election.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claim. Currently, the following claim(s) are generic: 10-20
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: the invention groups lack unity of invention because even though the inventions of these groups require the technical feature of a conjugate comprising bilirubin linked to chitosan, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Surendran et al. (Acta Biomaterialia 2020 116:356-367). Specifically, Surendran et al. teach a conjugate composed of bilirubin covalently linked to chitosan (see scheme 2). Surendran et al. further teach treating inflammatory aspects of hepatic fibrosis (inflammatory condition/disease) by administering the conjugate (see page 357 firs column first full paragraph). Therefore the common technical feature was known and does not qualify as a special technical feature. Thus the invention groups and species lack unity.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
During a telephone conversation and subsequent response from Kisuk Lee on September 5, 2025 a provisional election was made with traverse to prosecute the invention of group I and the species where the inflammatory disease is non-alcoholic steatohepatitis, claims 10-11 and 14-20. Affirmation of this election must be made by applicant in replying to this Office action. Claim 1-9 and 12-14 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Specification
The disclosure is objected to because of the following informalities: the specification lists figure 5 which shows the chemical structure of formula 1 and states that it is the bilirubin-chitosan conjugate made that had a weight proportion of 25% bilirubin (see paragraphs 153-158). The structure in formula 1 corresponds to the bilirubin composing 45% of the weight of each of its repeat units, thus formula 1 in figure 5 is not the structure of the conjugate that was made (as calculated by the examiner: formula 1 repeat unit = 1260 Da, bilirubin portion = 567 Da).
Appropriate correction is required.
Drawings
The drawings are objected to because: figure 52 depicts a reaction scheme that shows a precise chemical structure for a reaction product that would not result from the combination of reactants that is depicted. The product structure requires precise reaction locations on the chitosan reactant, but includes nothing that would control where reaction occurs amongst the primary amine functional groups along the length of the chitosan (see section Claim Rejections - 35 USC § 112 below for further detail of this issue that occurs in multiple places in the disclosure). A similar issue occurs in the more generically depicted reaction in figure 2A. Additionally, figure 5 recites a chemical structure that seemingly corresponds to the HNMR that was performed on a bilirubin-chitosan conjugate made in example 2. As noted in the Specification section above, this structure does not correspond to the bilirubin-chitosan conjugate that was made and characterized as having 25 wt% bilirubin.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 19 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant disclosure provides multiple “schematic” representations of the claimed conjugate and its synthesis (see figures 2A and 52). Chitosan is depicted as
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and shown to form the structure in formula 1
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by reaction with bilirubin
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in the presence of a solvent and 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC) (see paragraphs 19-23 and figure 52). As the specification notes, EDC facilitates reaction between primary amine groups and carboxyl groups to form amide linkages. The chitosan is shown to have a repeating pattern of a primary amine on three consecutive sugar groups and an acetylated amine on the fourth, yet formula 1 shows the bilirubin precisely bound only to the last of the series of free amine groups. This provides a regular pattern of bilirubin being located on every fourth sugar unit. The combination of these reactants provides no control over the particular available primary amine groups that serves as the site of reaction. There also is no discussion of protecting groups being employed to precisely shield all, but every fourth sugar unit’s primary amines to limit or steer the reaction locations. In addition, the stereochemistry depicted in the chitosan places the primary amines on adjacent sugar molecules in different planes which provides space to sterically accommodate bilirubin binding closer than every fourth sugar unit. Further, the disclosure recites formula 1 as the bilirubin-chitosan conjugate made and note a 25% weight proportion of bilirubin in this prepared conjugate (see paragraphs 153-158 and figure 5). However, the structure in formula 1 corresponds to the bilirubin composing 45% of the weight of each of its repeat units. Thus formula 1 is not the structure of the conjugate that was made (as calculated by the examiner: formula 1 repeat unit = 1260 Da, bilirubin portion = 567 Da). Since the assessed material does not match the schematic in formula 1 and no discussion of the preparation procedure for a compound with this structure was provided, the artisan of ordinary skill would not have deemed the applicant to be in possession of the conjugate of formula 1 as is instantly claimed at the time of filing.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 19 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claim recites formula 1 as
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It is not clear if this recitation is an actual chemical structure as it appears or it is a schematic representation of the sugar units that are present in some amount and in some arrangement in the claimed bilirubin-chitosan conjugate. As noted in the rejection under section (a) of this statute, the disclosure does not detail the steps that would be necessary to make a compound with the recited structure. Thus it is unclear what the depiction is meant to represent.
In addition, the formula 1 representation shows what appear to be extra bonds between substituents in the bilirubin originating portion. Some of them appear to show non-covalent interactions, where others look like covalent bonds that may be intended to depict non-covalent interactions as well
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Clarification is required.
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 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 10, 14-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Georgescu et al. (Journal of Gastrointestinal and Liver Disease 2007 16(1):39-46) in view of Surendran et al.
Georgescu et al. teach non-alcoholic steatohepatitis as a condition that can progress to cirrhosis and is characterized by the occurrence of inflammation and fibrosis in the liver (see page 40 first column first full paragraph). They go on to teach that administration of losartan is effective to treat and improve the condition (see page 41 first column first paragraph and second column last partial paragraph-page 42 first column and table IV). The inclusion of a bilirubin-chitosan conjugate as a carrier is not detailed.
Surendran et al. teach micelles composed of a covalently bound bilirubin-chitosan conjugate that include losartan (see abstract and schemas 1-2; instant claim 15). The conjugate has the chitosan and bilirubin linked via an amide bond formed between a carboxyl of bilirubin and an amine of chitosan (see page 363 second column third full paragraph and schema 2; instant claims 16-17). They detail that the bilirubin-chitosan conjugate has intrinsic anti-inflammatory activity and detail its utility as a treatment for liver fibrosis (see page 357 first column first full paragraph; instant claim 10). Surendran et al. additionally teach the micelles to be particularly suited for treating fibrosis in the liver due to their ability to release their cargo in the presence of reactive oxygen species that are known to be present in the diseased tissue (see page 357 first column first full paragraph). The micelles have a size ranging from 160 to 223 nm, as determined by dynamic light scattering, and are provided in a phosphate buffered saline carrier (see page 357 second column first full paragraph-page 358 first column first full paragraph and supplement figure 1; instant claims 10 and 20). Surendran et al. further detail intravenous administration (see page358 second column first full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat non-alcoholic steatohepatitis with losartan as taught by Georgescu et al. by administering the losartan loaded micelles of Surendran et al. to a patient in need thereof. This modification would have been obvious as the application of the same technique to a similar method in order to yield the same improvement (e.g., added anti-inflammatory activity and diseased tissue responsive release). Therefore claims 10, 14-17, and 20 are obvious over Georgescu et al. in view of Surendran et al.
Claims 10-11, 14-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Georgescu et al. in view of Surendran et al. as applied to claims 10, 14-17, and 20 above, and further in view of Jon et al. (US PGPub No. 2017/0028076).
Georgescu et al. in view of Surendran et al. render obvious the limitations of instant claims 10, 14-17, and 20, where losartan loaded nanoparticle micelles of bilirubin-chitosan conjugate are administered. Surendran et al. discuss administering losartan orally, but do not detail oral administration of the nanoparticle structure (see page 358 second column fist full paragraph).
Jon et al. teach conjugates of bilirubin and hydrophilic polymers that form nanoparticle carriers that are themselves therapeutic and serve as a carrier for additional desired therapeutic compounds (see abstract and paragraph). Chitosan is detailed as an envisioned hydrophilic polymer to bind to the bilirubin (see paragraph 35-37). Jon et al. further teach oral as well as parenteral administration of the nanoparticles (see paragraph 67).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method of Georgescu et al. in view of Surendran et al., where the bilirubin-chitosan conjugate nanoparticle micelles are administered orally in light of Jon et al. This modification would have been obvious because Jon et al. teach this administration route to be suitable for a similar conjugate in nanoparticle form. This modification is also obvious as the simple substitution of one known element for anther (e.g., oral vs intravenous administration routes). Therefore claims 10-11, 14-17, and 20 are obvious over Georgescu et al. in view of Surendran et al. and Jon et al.
Claims 10, 14-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Georgescu et al. in view of Surendran et al. as applied to claims 10, 14-17, and 20 above, and further in view of Lee et al. (Act Biomaterialia 2017 57:262-273).
Georgescu et al. in view of Surendran et al. render obvious the limitations of instant claims 10, 14-17, and 20, where losartan loaded nanoparticle micelles of bilirubin-chitosan conjugate are administered. The chitosan is not detailed with the instantly recited molecular weight.
Lee et al. teach a chitosan conjugate as a nanoparticle forming drug carrier that self-assembles into a micelle like structure having a hydrophilic shell and more hydrophobic core (see abstract and page 263 first column second full paragraph and figure 3A). Here they detail the chitosan to be chitosan oligosaccharide, as the instant example 1 also employs, where the amine of the chitosan is bound to the carboxyl group of its partner compound in the conjugate, as is done in the conjugate of Surendran et al. (see figure 2A). The chitosan oligosaccharide employed has a molecular weight of about 5 kD (see page 263 second column last partial paragraph-267 first column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the chitosan oligosaccharide of Lee et al. to prepare the bilirubin-chitosan conjugate of Georgescu et al. in view of Surendran et al. because it was known to be employed in the same way to yield a nanoparticle forming conjugate that carries the activity of its constituents and is able to carry an additional drug as cargo. The modification is also obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g., specific chitosan vs generic chitosan). Therefore claims 10, 14-18, and 20 are obvious over Georgescu et al. in view of Surendran et al. and Lee et al.
Claims 10-11, 14-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Jon et al. in view of Lau et al. (US PGPub No. 2019/0321377), Tacke (Expert Opinion on Investigational Drugs 2018 27(3): 301-311).
Jon et al. teach nanoparticles capable of precision, location specific triggered release of its cargo (see paragraph 2 and 9). Specifically, they detail conjugates of bilirubin and hydrophilic polymers that self assemble to form nanoparticle carriers that are themselves therapeutic and serve as carriers for additional desired therapeutic compounds (see abstract and paragraph 9). Chitosan is detailed as an envisioned hydrophilic polymer to bind to the bilirubin (see paragraphs 35-37). The conjugate is formed from covalent binding between an amine of the hydrophilic polymer and a carboxyl of the bilirubin which yields an amide covalent bond (see paragraphs 41-42; instant claim 15-17). The nanoparticles have a size of 50 to 1000 nm and are measured via dynamic light scattering (see paragraphs 23 and 120; instant claim 20). Jon et al. further teach oral administration of the nanoparticles (see paragraph 67). The nanoparticles are sensitive to light and the reactive oxygen species present in an inflammatory environment thereby permitting both avenues to guide delivery of their cargo at sites of inflammation (see paragraphs 21-31). Envisioned drug cargo include anti-inflammatory agents (see paragraph 25). Jon et al go on to teach hepatitis as an inflammatory condition to treat with their composition, where the nanoparticles may be included in a pharmaceutical acceptable carrier and delivered parenterally as well as orally (see paragraphs 55 and 66-67; instant claims 10 and 11). Treating non-alcoholic steatohepatitis is not explicitly detailed.
Lau et al. teach that non-alcoholic steatohepatitis is an inflammatory condition mediated by C-C Chemokine receptor 5/C-C Chemokine receptor 2 (see claims 1-2; instant claims 10 and 14). They additionally teach C-C Chemokine receptor 5/C-C Chemokine receptor 2 antagonist compounds to administer to treat such conditions and name cenicriviroc (see claims 23 and 38).
Tacke et al. teach the administration of the anti-inflammatory compound cencirviroc to treat non-alcoholic steatohepatitis was found to be an effective treatment (see abstract and page 307 first column second full paragraph-second column first partial paragraph). They detail that non-alcoholic steatohepatitis as characterized by the occurrence of inflammation and fibrosis in the liver (see page 301 first column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the nanoparticles of Jon et al. where chitosan is the hydrophilic polymer because they explicitly recite it as an envisioned option. It would have also been obvious to administer the nanoparticles to treat a hepatitis and specifically non-alcoholic steatohepatitis which Lau et al. identify as an inflammatory condition. Since Jon et al. envision anti-inflammatory drug cargo and Lau et al teach cenicriviroc as an anti-inflammatory compounds that Tacke confirms is effectiveness against non-alcoholic steatohepatitis, it would have further been obvious to include cenicriviroc in the nanoparticles. It would follow to administer the nanoparticles via the carrier and routes taught by Jon et al. Therefore claims 10-11, 14-17, and 20 are obvious over Jon et al. in view of Lau et al. and Tacke.
Claims 10, 14-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Jon et al. in view of Lau et al. and Tacke as applied to claims 10-11, 14-17, and 20 above, and further in view of Lee et al.
Jon et al. in view of Lau et al. and Tacke render obvious the limitations of instant claims 10-11, 14-17, and 20, where cenicriviroc loaded nanoparticles of bilirubin-chitosan conjugate are administered. The chitosan is not detailed with the instantly recited molecular weight.
Lee et al. teach a chitosan conjugate as a nanoparticle forming drug carrier that self-assembles into a micelle like structure having a hydrophilic shell and more hydrophobic core (see abstract and page 263 first column second full paragraph and figure 3A). Here they detail the chitosan to be chitosan oligosaccharide, as the instant example 1 also employs, where the amine of the chitosan is bound to the carboxyl group of its partner compound in the conjugate, as is done in the conjugate of Jon et al. (see figure 2A). The chitosan oligosaccharide employed has a molecular weight of about 5 kD (see page 263 second column last partial paragraph-267 first column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the chitosan oligosaccharide of Lee et al. to prepare the bilirubin-chitosan conjugate of Jon et al. in view of Lau et al. and Tacke because it was known to be employed in the same way to yield a nanoparticle forming conjugate that carries the activity of its constituents and is able to carry an additional drug as cargo. The modification is also obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g., specific chitosan vs generic chitosan). Therefore claims 10-11, 14-18, and 20 are obvious over Jon et al. in view of Lau et al., Tacke, and Lee et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 10-11, 14-17, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6, 10, and 12-13 of U.S. Patent No. 11,904,019 in view of Lau et al., Tacke, and Jon et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim treating an inflammatory condition by administering nanoparticles composed of a conjugate of bilirubin and a hydrophilic polymer recited to be chitosan to a patient in need thereof. The conjugate is formed from covalent binding between an amine of the hydrophilic polymer, that is claimed as chitosan, and a carboxyl of the bilirubin. The patented claims also include an anti-inflammatory agent as a cargo compound in the nanoparticles. Treating non-alcoholic steatohepatitis is not explicitly recited.
Lau et al. teach that non-alcoholic steatohepatitis is an inflammatory condition mediated by C-C Chemokine receptor 5/C-C Chemokine receptor 2 (see claims 1-2). They additionally teach C-C Chemokine receptor 5/C-C Chemokine receptor 2 antagonist compounds to administer to treat such conditions and name cenicriviroc (see claims 23 and 38).
Tacke et al. teach the administration of the anti-inflammatory compound cencirviroc to treat non-alcoholic steatohepatitis was found to be an effective treatment (see abstract and page 307 first column second full paragraph-second column first partial paragraph). They detail that non-alcoholic steatohepatitis as characterized by the occurrence of inflammation and fibrosis in the liver (see page 301 first column).
Jon et al. teach nanoparticles capable of precision, location specific triggered release of its cargo (see paragraph 2 and 9). Specifically, they detail conjugates of bilirubin and hydrophilic polymers that self assemble to form nanoparticle carriers that are themselves therapeutic and serve as carriers for additional desired therapeutic compounds (see abstract and paragraph 9). Chitosan is detailed as an envisioned hydrophilic polymer to bind to the bilirubin (see paragraphs 35-37). The conjugate is formed from covalent binding between an amine of the hydrophilic polymer and a carboxyl of the bilirubin which yields an amide covalent bond (see paragraphs 41-42). The nanoparticles have a size of 50 to 1000 nm and are measured via dynamic light scattering (see paragraphs 23 and 120;). Jon et al. further teach oral administration of the nanoparticles (see paragraph 67). Jon et al. go on to teach that the nanoparticles may treat hepatitis and be included in a pharmaceutical acceptable carrier to facilitate delivery parenterally as well as orally (see paragraphs 55 and 66-67).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of the patented claims where the inflammatory condition is non-alcoholic steatohepatitis and the anti-inflammatory cargo compound is cenicriviroc. These choices would have been obvious in light of Lau et al. who teach the condition as a recognized inflammatory condition able to be thwarted with cenicriviroc as a known anti-inflammatory agent and Tacke who teach cenicriviroc’s effectiveness in this capacity. Covalent linkage between the bilirubin and chitosan would have been obvious because it is recited amongst the product claims, in spite of not appearing in the method lineage. Further, it would have been obvious to make the nanoparticles with sizes and in a carrier as detailed by Jon et al. would have been obvious because they also teach bilirubin conjugate nanoparticles intended to treat a hepatitis condition at their taught size that are administered via carrier. Therefore claims 10-11, 14-17, and 20 are obvious over claims 1, 3-4, 6, 10, and 12-13 of U.S. Patent No. 11,904,019 in view of Lau et al., Tacke, and Jon et al.
Claims 10-11, 14-18, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6, 10, and 12-13 of U.S. Patent No. 11,904,019 in view of Lau et al., Tacke, and Surendran et al. as applied to claims 10-11, 14-17, and 20 above, and further in view of Lee et al.
Claims 1, 3-4, 6, 10, and 12-13 of U.S. Patent No. 11,904,019 in view of Lau et al., Tacke, and Jon et al. render obvious the limitations of instant claims 10-11, 14-17, and 20, where drug loaded nanoparticles of bilirubin-chitosan conjugate are administered. The chitosan is not detailed with the instantly recited molecular weight.
Lee et al. teach a chitosan conjugate as a nanoparticle forming drug carrier that self-assembles into a micelle like structure having a hydrophilic shell and more hydrophobic core (see abstract and page 263 first column second full paragraph and figure 3A). Here they detail the chitosan to be chitosan oligosaccharide, as the instant example 1 also employs, where the amine of the chitosan is bound to the carboxyl group of its partner compound in the conjugate, as is done in the conjugate of Surendran et al. (see figure 2A). The chitosan oligosaccharide employed has a molecular weight of about 5 kD (see page 263 second column last partial paragraph-267 first column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the chitosan oligosaccharide of Lee et al. to prepare the bilirubin-chitosan conjugate of the modified patented claims because it was known to be employed in the same way to yield a nanoparticle forming conjugate that carries the activity of its constituents and is able to carry an additional drug as cargo. The modification is also obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g., specific chitosan vs generic chitosan). Therefore claims 10-11, 14-18, and 20 are obvious over claims 1, 3-4, 6, 10, and 12-13 of U.S. Patent No. 11,904,019 in view of Lau et al., Tacke, Jon et al., and Lee et al.
Conclusion
No claim is allowed.
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/CARALYNNE E HELM/ Examiner, Art Unit 1615