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 .
Status of Application, Amendments and/or Claims
The amendment of 05 February 2025 has been entered in full. Claims 5-8, 12, 13, 15, 16, 18, 24, 40, 41, 47, 51, and 54 are amended. Claims 4, 9-11, 14, 19-23, 25-39, 42-46, 48-50, and 52 are cancelled.
Claims 1-3, 5-8, 12, 13, 15-18, 24, 40, 41, 47, 51, and 54 are under consideration in the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 21 October 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
1. The drawings are objected to because the instant drawings do not comply with 37 C.F.R. § 1.84(U)(1), which states that partial views of a drawing which are intended to form one complete view, whether contained on one or several sheets, must be identified by the same number followed by a capital letter. Figure 6B of the instant application, for example, is presented on 2 separate pages and the Figure labeled as “Figure 6B continued” should be renumbered as “Figure 6C”.
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.
Applicant is reminded that once the drawings are changed to meet the separate numbering requirement of 37 C.F.R. 1 1.84(U)(1), Applicant is required to file an amendment to change the Brief Description of the Drawings and the rest of the specification accordingly.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
2. SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
2a. Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
3. The disclosure is objected to because of the following informalities:
3a. The Brief Description of the Drawings (at page 8, [0034]) does not refer to Figures 8A, 8B, and 8C.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
4. Claims 5, 6, and 17 are 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.
4a. Claims 5 and 6 recite the limitation "the TIMP-PBC particles" in line 2. There is insufficient antecedent basis for this limitation in the claims. Claim 1, from which claims 5 and 6 depend, only recites “administering to the subject tolerizing immune modifying particles encapsulating one or more PBC antigens (TIMP-PBC)”. Claim 1 does not specifically recite “TIMP-PBC particles”.
4b. Regarding claim 17, the phrase “(ALT, ALP, AST, γ-glutamyl transpeptidase)” after “elevated liver enzyme levels” renders the claim indefinite because it is unclear whether the limitations in the parentheses are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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 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.
Shea et al. (evidenced by Joplin et al. and Gao et al.)
5. Claims 1, 2, 5-8, 12, 13, 15-18, 24, 47, 51, 52, and 54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shea et al. (US 2015/0190485), as evidenced by Joplin et al. (Hepatol 19(6): 1375-1380, 1994) and Gao et al. (Clin Rev Allergy Immunol 59(2):175-194, 2020; cited on the IDS of 21 October 2024).
Shea et al. teach compositions (e.g. for induction of antigen-specific tolerance) comprising a carrier particle attached to an antigenic peptide (page 2, [0013]). Shea et al. disclose compositions comprising an antigen coupled to a carrier particle with a negative zeta potential, wherein the zeta potential is from about -100 mV to about 0 mV, meeting the limitations of instant claims 6 and 7 (page 2, [0013]). Shea et al. state that the particle has an average diameter of between 0.1 μm to about 10 μm (or 100 nm to 1000 nm), meeting the limitations of instant claim 5 (page 2, [0015]). Shea et al. teach that the antigen is encapsulated in the particle, meeting the limitations of instant claim 1 (page 1, [0011]; page 3, [0020]; page 14, [0143]).
Shea et al. disclose that the antigen can be autoantigen that comprises at least a portion of pyruvate dehydrogenase dehydrolipoamide acetyltransferase (PCD-E2), which is also known as PDC-E2, meeting the limitations of instant claim 2 (see Shea et al., page 2, [0016-0017], page 16, [0160]; Joplin et al., page 1375, column 2, 1st full paragraph).
Shea et al. teach that the antigen can be used in treating primary biliary cirrhosis [also known as primary biliary cholangitis], meeting the limitations of instant claims 1 and 16-18 (see Shea et al., page 3, [0021]; page 16, [0160]; pages 24-25, [0214];; Gao et al., page 176, column 2, 1st paragraph).
Shea et al. disclose that the particles may be administered orally, nasally, intravenously, intramuscularly, ocularly, transdermally, intraperitoneally, or subcutaneously, meeting the limitations of instant claim 15 (page 21, [0188]). Shea et al. also indicate that a suitable dosage range may be, for example, from about any of the following: 0.5 to 10 mg/kg, 1 to 9 mg/kg, 2 to 8 mg/kg, 3 to 7 mg/kg, 4 to 6 mg/kg, 5 mg/kg, 1 to 10 mg/kg, 5 to 10 mg/kg, meeting the limitations of instant claim 8 (page 21, [0189]).
Shea et al. indicate when multiple administrations are performed, the time between administrations is generally between 1 day and 3 weeks, meeting the limitations of instant claims 12 and 13 (page 20, [0175-0176]). Shea et al. specifically disclose that the invention includes embodiments of tolerance on a schedule of administrations that occur semiweekly, weekly, biweekly, or on any other regular schedule, meeting the limitations of instant claims 12 and 13 (page 20, [0176]).
Shea et al. teach that pharmaceutical compositions containing the particles of the invention can be formulated and employed in combination therapies, such as IL-10 and TGF-β, meeting the limitations of instant claims 47, 51, 52, and 54 (page 24, [0208]; page 23, [0199]).
Shea et al. teach administration of PDC-E2 particles to the same subject population (subjects with primary biliary cholangitis) as required by the instant claims. Therefore, one or more of the therapeutic results/characteristics recited in instant claim 24 would inherently occur in the prior art of Shea et al., absent evidence to the contrary (see Ex parte Novitski, 26 USPQ2d 1389 (BPAI 1993) ; see also Integra LifeSciences I Ltd. V. Merck KGaA, (DC SCalif) 50 USPQ2d 1846; In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)). The broad method steps claimed in the instant application are the same as the steps disclosed in Shea et al. Thus, Shea et al. anticipates the claimed invention of the instant application. Furthermore, inherent anticipation does not require that one of ordinary skill in the art recognize an inherent feature in a prior art disclosure (Schering Corp. v. Geneva Pharmaceuticals Inc., 67 USPQ2d 1664 (CAFC 2003); Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004)). A compound and all of its properties are inseparable; they are one and the same thing and simply stating a property of PDC-E2 particles (see claim instant claim 24) does not render the claimed method of treating primary biliary cholangitis of the instant application free of the art (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169 USPQ 226 (CCPA 1971); In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)). MPEP 2111(I) states that “the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Additionally, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)).
Santamaria
6. Claims 1, 2, 5, 8, 12, 13, 15-18, 24, 40, 41, and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Santamaria, P. (WO 2020/237160; published 26 November 2020).
Santamaria teaches a composition for use in treating a hepatic inflammatory disease, the composition comprising: (a) a plurality of antigen-major histocompatibility complexes (antigen-MHCs), each antigen-MHC of the plurality comprising a ubiquitous autoantigen associated with a binding groove of an MHC molecule; and (b) a nanoparticle core possessing a diameter of between 1 and about 100 nanometers, wherein the antigen-MHCs are coupled to the nanoparticle core, meeting the limitations of instant claim 5 (page 1, [0004]; page 3, [0005]; page 12, [0033-0034]). Santamaria discloses that the ubiquitous autoantigen is pyruvate dehydrogenase complex-E2 (PDC-E2), meeting the limitations of instant claim 2 (middle-bottom of page 2, [0004] through the top of page 3). Santamaria teaches a method of treating a hepatic inflammatory disease in an individual (page 3, [0005]; page 12, [0033-0034]). Santamaria discloses the administration of PDC-E2 nanoparticles to a mouse model of primary biliary cholangitis and a reduction in signs of disease, meeting the limitations of instant claims 1 and 51 (page 43, [00135]; page 46, [00144]; Figure 4A-4I; pages 53-54, Example 10). Santamaria indicates that treatment suppresses liver inflammation and fibrosis, meeting the limitations of instant claims 16-18, 40, and 41 (page 54, [00166]; page 57, [00176]; Figure 13A-13C).
Santamaria states that a single dose of the ubiquitous autoantigen-MHC-NP comprises about 0.001 mg/kg to about 2.0 mg/kg, meeting the limitations of instant claims 1 and 8 (pages 39-40, [00128]).
Santamaria teaches that it may be desirable to have multiple administrations of a ubiquitous autoantigen-MHC-NP, about, at least about, or at most about 3, 4, 5, 6, 7, 8, 9, 10 or more administrations, meeting the limitations of instant claim 12 (page 39, [00127]). Santamaria continues to indicate that the administrations will normally range from 1, 2, 3, 4, 5, 6, or 7 day to twelve week intervals, more usually from one to two week intervals, meeting the limitations of instant claim 13 (page 39, [00127]). Santamaria states that periodic boosters at intervals of every other day, twice a week, weekly, biweekly, monthly, or 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3,4 or 5 years, usually two years, will be desirable to maintain the condition of the immune system, meeting the limitations of instant claim 13 (page 39, [00127]).
Santamaria discloses that the ubiquitous autoantigen-MHC-NP can be formulated for intravenous injection, oral ingestion, parenteral administration, intramuscular injection, subcutaneous injection, or other intra tissue injection, meeting the limitations of instant claim 15 (page 43, [00133]).
Santamaria teaches administration of PDC-E2 nanoparticles to the same subject population (subjects with primary biliary cholangitis) as required by the instant claims. Therefore, one or more of the therapeutic results/characteristics recited in instant claim 24 must have been inherently occurring in the prior art of Santamaria, absent evidence to the contrary (see Ex parte Novitski, 26 USPQ2d 1389 (BPAI 1993) ; see also Integra LifeSciences I Ltd. V. Merck KGaA, (DC SCalif) 50 USPQ2d 1846; In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)). The broad method steps claimed in the instant application are the same as the steps disclosed in Santamaria. Thus, Santamaria anticipates the claimed invention of the instant application. Furthermore, inherent anticipation does not require that one of ordinary skill in the art recognize an inherent feature in a prior art disclosure (Schering Corp. v. Geneva Pharmaceuticals Inc., 67 USPQ2d 1664 (CAFC 2003); Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004)). A compound and all of its properties are inseparable; they are one and the same thing and simply stating a property of PDC-E2 nanoparticles (see claim instant claim 24) does not render the claimed method of treating primary biliary cholangitis of the instant application free of the art (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169 USPQ 226 (CCPA 1971); In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)). MPEP 2111(I) states that “the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Additionally, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)).
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.
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.
Shea et al. and Surh et al.
7. Claims 1-3, 5-8, 12, 13, 15-18, 24, 47, 51, 52, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Shea et al. (US 2015/0190485) (as evidenced by Joplin et al. (Hepatol 19(6): 1375-1380, 1994) and Gao et al. (Clin Rev Allergy Immunol 59(2):175-194, 2020; cited on the IDS of 21 October 2024)) and Surh et al. (J Immunol 144(9): 3367-3374, 1990).
The teachings of Shea et al., Joplin et al., and Gao et al. are set forth above.
Shea et al. do not teach that the antigen comprising at least a portion of PDC-E2 comprises PDC-E2 amino acid residues 155-185 (SEQ ID NO: 1).
Surh et al. teach that the E2 component (acetyltransferase) of the pyruvate dehydrogenase (PDH) complex is the major mitochondrial autoantigen recognized by autoantibodies in patients with primary biliary cirrhosis (PBC) [also known as primary biliary cholangitis] (Surh et al., abstract). Surh et al. disclose that the dominant human PDH-E2 domain epitope is localized to the inner lipoyl domain (abstract). Surh et al. continue to disclose that through probing recombinant fusion proteins expressed from restriction fragments of the lipoyl domain, a minimum of 75 amino acids (residues 76-221) is required for detectable autoantibody binding (abstract). Additionally, Surh et al. state that 93 amino acids (residues 128-221) are necessary for characteristically strong antimitochondrial autoantibody recognition (abstract; Table II).
It is noted that the lipoyl domain amino acid epitopes of 76-221 or 128-221 of human PDH-E2 of Surh et al. comprise PDC-E2 amino acids 155-185 (SEQ ID NO: 1) as required by instant claim 3 (see page 372, Figure 9(B); KVGEKLSEGDLLAEIETDKATIGFEVQEEGY).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the composition comprising a carrier particle attached to an antigenic peptide, wherein the antigenic peptide comprises a portion of PDC-E2 (and methods of administering such) as taught by Shea et al. by utilizing the lipoyl domain amino acid epitope of 76-221 or 128-221 of human PDC-E2 as taught by Surh et al. The person of ordinary skill in the art would have been motivated to make that modification because amino acids 76-221 or 128-221 of human PDC-E2 are specific autoantigens in patients with primary biliary cholangitis (Surh et al., abstract; Table II; page 3368, column 1, 1st full paragraph). Furthermore, the design of a specific PDC-E2-nanoparticle immunotherapy for induction of antigen-specific tolerance could be used to treat the autoimmune disease, primary biliary cholangitis, without long-term administration of broad-acting immunosuppressive drugs that have toxic side effects (Shea et al., page 1, [0009]; page 2, [0013]; page 16, [0160]). The person of ordinary skill in the art reasonably would have expected success because antigen-conjugated particles were already being successfully generated and administered at the time the invention was made (see entirety of Shea et al.). Additionally, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)). Therefore, the claimed invention as a whole was clearly prima facie obvious over the prior art.
Santamaria and Surh et al.
8. Claims 1-3, 5, 8, 12, 13, 15-18, 24, 40, 41, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Santamaria, P. (WO 2020/237160; published 26 November 2020) and Surh et al. (J Immunol 144(9): 3367-3374, 1990).
The teachings of Santamaria are set forth above.
Santamaria does not teach that the administered ubiquitous autoantigen-MHC-nanoparticle (NP) comprising PDC-E2 as the ubiquitous autoantigen utilizes PDC-E2 comprising amino acid residues 155-185 (SEQ ID NO: 1).
Surh et al. teach that the E2 component (acetyltransferase) of the pyruvate dehydrogenase (PDH) complex is the major mitochondrial autoantigen recognized by autoantibodies in patients with primary biliary cirrhosis (PBC) [also known as primary biliary cholangitis] (Surh et al., abstract). Surh et al. disclose that the dominant human PDH-E2 domain epitope is localized to the inner lipoyl domain (abstract). Surh et al. continue to disclose that through probing recombinant fusion proteins expressed from restriction fragments of the lipoyl domain, a minimum of 75 amino acids (residues 76-221) is required for detectable autoantibody binding (abstract). Additionally, Surh et al. state that 93 amino acids (residues 128-221) are necessary for characteristically strong antimitochondrial autoantibody recognition (abstract; Table II).
It is noted that the lipoyl domain amino acid epitopes of 76-221 or 128-221 of human PDH-E2 of Surh et al. comprise PDC-E2 amino acids 155-185 (SEQ ID NO: 1) as required by instant claim 3 (see page 372, Figure 9(B); KVGEKLSEGDLLAEIETDKATIGFEVQEEGY).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the ubiquitous PDC-E2-MHC-NP (and methods of administering such) as taught by Santamaria by utilizing the lipoyl domain amino acid epitope of 76-221 or 128-221 of human PDC-E2 as taught by Surh et al. The person of ordinary skill in the art would have been motivated to make that modification because amino acids 76-221 or 128-221 of human PDC-E2 are specific autoantigens in patients with primary biliary cholangitis (Surh et al., abstract; Table II; page 3368, column 1, 1st full paragraph). Furthermore, the design of a specific PDC-E2-MHC-NP immunotherapy for induction of antigen-specific tolerance could be used to treat the autoimmune disease, primary biliary cholangitis, without increasing a treated patient’s risk for developing secondary infections and systemic immunological complications (Santamaria, page 1, [0003]). The person of ordinary skill in the art reasonably would have expected success because PDC-E2-MHC-NP were already being successfully generated and administered at the time the invention was made (see entirety of Santamaria). Additionally, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)). Therefore, the claimed invention as a whole was clearly prima facie obvious over the prior art.
Santamaria and Aguilar et al.
9. Claims 1, 2, 5, 8, 12, 13, 15-18, 24, 40, 41, 47, 51, 52, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Santamaria, P. (WO 2020/237160; published 26 November 2020) and Aguilar et al. (Hepatic Medicine: Evidence and Res 12: 69-77, 2020; cited on the IDS of 21 October 2024).
The teachings of Santamaria are set forth above.
Santamaria does not teach a method of treating a hepatic inflammatory disease, such as primary biliary cholangitis (PBC), by administering PDC-E2 nanoparticles in combination with an additional therapeutic.
Aguilar et al. teach that standard care for PBC includes treatment with Ursodeoxycholic Acid (UDCA), a synthetic bile acid (page 70, entire column 1; Table 1). Aguilar et al. disclose that UDCA halts the progression of fibrosis leading to longer transplant-free survival (page 74, column 2, last paragraph).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the method of treating a hepatic inflammatory disease, such as PBC, comprising administering PDC-E2 nanoparticles as taught by Santamaria by also administering UDCA, as taught by Aguilar et al. The person of ordinary skill in the art would have been motivated to make that modification to enhance the success of treatment of PBC, as it is widely accepted that PBC is a rare autoimmune cholestatic liver disease with limited treatment options (Aguilar et al., abstract). The skilled artisan also would have been motivated to make that modification because both the PDC-E2 nanoparticles and UDCA are separately disclosed to treat PBC. “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.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP § 2144.06. Additionally, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)). Therefore, the claimed invention as a whole was clearly prima facie obvious over the prior art.
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.
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10. Claims 1-3, 5-,8 12, 13, 15-18, 24, 40, 41, 47, 51, 52, and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 10, 15, 17, 25, 35-37, 39, 44, 45, 47, 64, 65, 67-70, 73, 74, and 81 of copending Application No. 19/485,809 in view of Santamaria, P. (WO 2020/237160; published 26 November 2020) and Aguilar et al. (Hepatic Medicine: Evidence and Res 12: 69-77, 2020; cited on the IDS of 21 October 2024).
Claim 1 of the instant application is directed to a method of treating primary biliary cholangitis (PBC) in a subject comprising administering to the subject tolerizing immune modifying particles encapsulating one or more PBC antigens (TIMP-PBC), wherein TIMP-PBC is administered at a dose level of between about 0.01 mg/kg and 12 mg/kg.
Meanwhile, claim 64 of the ‘809 application, for example, recites a composition comprising particles encapsulating one or more primary biliary cholangitis (PBC)-associated antigens. Claim 69 of ‘809 recites a pharmaceutical composition comprising negatively charged particles encapsulating PDC-E2155-185 peptide, sucrose, mannitol, and sodium citrate. Claim 70 recites negatively charged particles comprise poly(lactic co-glycolic acid) (PLGA) and PDC-E2155-185 peptide, wherein the PDC-E2155-185 peptide amount is between 0.1 µg/mg and 100
µg/mg or between 1 µg/mg to 5 µg/mg. Claim 81 of the ‘809 application recites a method of treating a subject having primary biliary cholangitis comprising administering a composition comprising particles encapsulating one or more primary biliary cholangitis (PBC)-associated antigens.
It is noted that the PDC-E2155-185 peptide of the claims of the ‘809 application is 100% identical to the PDC-E2 amino acid residues 155-185 (SEQ ID NO: 1) of the instant claims.
Instant claim 5 recites that the TIMP-PBC particles have an average diameter of between 100 nm and 1500 nm. Claim 47 of the ‘809 application recites that the particles have a diameter of between about 0.3 μm to 3 μm [300 nm to 3000 nm], between about 0.3 μm to 1 μm [300 nm to 1000 nm], or between about 0.4 μm to 1 μm [400 nm to 1000 nm].
Claims 6-7 of the instant application and claims 44-45 and 74 of the ‘809 recite that the particles have a negative zeta potential.
The claims of the ‘809 application do not recite the concentration of particles encapsulating PDC-E2 as recited in instant claim 5. The claims of the ‘809 application also do not recite the timing of administration or administration in combination with an additional therapeutic.
Santamaria also teaches a composition for use in treating a hepatic inflammatory disease, the composition comprising: (a) a plurality of antigen-major histocompatibility complexes (antigen-MHCs), each antigen-MHC of the plurality comprising a ubiquitous autoantigen associated with a binding groove of an MHC molecule; and (b) a nanoparticle core possessing a diameter of between 1 and about 100 nanometers, wherein the antigen-MHCs are coupled to the nanoparticle core (page 1, [0004]; page 3, [0005]; page 12, [0033-0034]). Santamaria discloses that the ubiquitous autoantigen is pyruvate dehydrogenase complex-E2 (PDC-E2) (middle-bottom of page 2, [0004] through the top of page 3). Santamaria teaches a method of treating a hepatic inflammatory disease in an individual (page 3, [0005]; page 12, [0033-0034]). Santamaria discloses the administration of PDC-E2 nanoparticles to a mouse model of primary biliary cholangitis and a reduction in signs of disease (page 43, [00135]; page 46, [00144]; Figure 4A-4I; pages 53-54, Example 10). Santamaria indicates that treatment suppresses liver inflammation and fibrosis (page 54, [00166]; page 57, [00176]; Figure 13A-13C).
Santamaria states that a single dose of the ubiquitous autoantigen-MHC-NP comprises about 0.001 mg/kg to about 2.0 mg/kg (pages 39-40, [00128]). Santamaria teaches that it may be desirable to have multiple administrations of a ubiquitous autoantigen-MHC-NP, about, at least about, or at most about 3, 4, 5, 6, 7, 8, 9, 10 or more administrations (page 39, [00127]). Santamaria continues to indicate that the administrations will normally range from 1, 2, 3, 4, 5, 6, or 7 day to twelve week intervals, more usually from one to two week intervals (page 39, [00127]). Santamaria states that periodic boosters at intervals of every other day, twice a week, weekly, biweekly, monthly, or 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3,4 or 5 years, usually two years, will be desirable to maintain the condition of the immune system (page 39, [00127]).
Santamaria discloses that the ubiquitous autoantigen-MHC-NP can be formulated for intravenous injection, oral ingestion, parenteral administration, intramuscular injection, subcutaneous injection, or other intra tissue injection (page 43, [00133]).
Aguilar et al. teach that standard care for PBC includes treatment with Ursodeoxycholic Acid (UDCA), a synthetic bile acid (page 70, entire column 1; Table 1). Aguilar et al. disclose that UDCA halts the progression of fibrosis leading to longer transplant-free survival (page 74, column 2, last paragraph).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the composition comprising particles encapsulating PDC-E2155-185 peptide antigen and the method of treating primary biliary cholangitis as recited by the claims of the ‘809 application by formulating the composition in specific concentrations and administering such over a period of weeks, months, or years and in combination with an additional PBC therapeutic, such UDCA, as taught by Santamaria and Aguilar et al. The person of ordinary skill in the art would have been motivated to modify the dosage and timing administration of the composition of the ‘809 application claims to improve upon what is already known, thus determining the optimum dosing and timing of administration. The person of ordinary skill in the art reasonably would have expected success because the optimization of dosage/concentration and dosing schedule is routine in the art. See In re Aller 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) "[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". See also In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). See also In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Furthermore, one skilled in the art would have been motivated to administer a composition comprising particles encapsulating PDC-E2155-185 peptide antigen of the ‘809 claims in combination with an additional PBC therapeutic, such UDCA, to enhance the success of treatment of PBC, as it is widely accepted that PBC is a rare autoimmune cholestatic liver disease with limited treatment options (Aguilar et al., abstract). The skilled artisan also would have been motivated to make that modification because both the particles encapsulating PDC-E2155-185 peptide antigen of the ‘809 claims and UDCA are separately disclosed to treat PBC. “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.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP § 2144.06. Additionally, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)).
Conclusion
No claims are allowable.
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BEB
Art Unit 1647
24 September 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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