DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Election/Restriction
Applicant’s election without traverse of poly(maleic acid-alt-1-octadecene), a combination of the peptides of SEQ ID NO: 1, 2, 3, and 4, D-mannitol, tris(hydroxymethyl)amino methane (Tris), and L-lactic acid in the reply filed on 22 April 2026, is acknowledged.
Status of Claims
The preliminary amendment, filed on 22 April 2026, is acknowledged.
Claim 1 is amended.
Claims 2-16 are cancelled.
New claims 17-43 have been added.
Claims 1 and 17-43 are pending in the instant Office Action.
Newly submitted claims 42-43 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Originally presented claims 1-16 were drawn to a pharmaceutical composition. Newly submitted claims 17-41 are similarly drawn to a pharmaceutical composition whereas newly submitted claims 42-43 are drawn to a method of treating Pemphigus vulgaris.
The invention of claims 1 and 17-41 is drawn to a product and the invention of claims 42-43 is drawn to a process of use. The invention of claims 1 and 17-41 does not share a special technical feature with the invention of claims 42-43 in view of the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster (vide infra). See PCT Rule 13.1 and 13.2.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 42-43 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Notice on Rejoinder
The examiner has required restriction between product 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.
Claims 1 and 17-41 are under consideration in the instant Office Action.
Priority
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of parent European Patent Application No. EP 21191798.4, filed on 17 August 2021, has been received from the International Bureau.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 February 2024, was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 26-28 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 26 recites the amino acid sequences of the 1st-4th peptides recited in instant claim 1 as consisting of the amino acid sequences of SEQ ID NO:1-4, respectively, in the alternative (i.e., “and/or”). Claim 1 requires all four of the peptides of SEQ ID Nos:1-4, however, the “and/or” language in claim 26 permits for fewer than all four sequences to be present, which would omit the limitation in claim 1 that requires all four sequences to be present. Thus, claim 26 broadens the scope of claim 1 and therefore does not further limit. A dependent claim must be rejected under 35 U.S.C. 112(d) if it omits an element from the claim upon which it depends or it fails to add a limitation to the claim upon which it depends. Amending claim 26 to remove the “or” and therefore require all four sequences consistent with claim 1 would overcome this rejection. Claims 27-28 are also included in the rejection as depending from claim 26.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 1, 17-24, 26-32, 34-35, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Eming et al. (European Patent Publication No. EP 2979704 A1, published on 3 February 2016, provided by Applicant in the IDS filed on 16 February 2024, references to English translation, hereafter referred to as Eming) in view of Veldman et al. (J. Immunol. 2004, 172 (6), 3883., hereafter referred to as Veldman), Payne et al. (U.S. Patent No. 10,301,370 B2, published on 28 May 2019, hereafter referred to as Payne), Mohapatra et al. (U.S. Patent Application No. US 2020/0049700 A1, published on 13 February 2020, hereafter referred to as Mohapatra), Herkel et al. (European Patent Application Publication No. EP 2591801 A1, published on 15 May 2013, hereafter referred to as Herkel), and Wooster et al. (WIPO International Publication No. WO 2017/136652 A1, published on 10 August 2017, hereafter referred to as Wooster).
Eming teaches the use of a medical preparation containing peptides of human desmoglein 3 (Dsg 3) to treat pemphigus vulgaris (PV) (Abstract). The administration of a medical preparation comprising peptides of Dsg 3 is taught to trigger “a desmoglein 3-specific immune tolerance in humans” and Eming notes that the peptides of Dsg 3 may be administered individually or in a combination to trigger the immune tolerance (pg. 1, final 2 para.). This is achieved by influencing the function of Dsg 3-reactive CD4 + T cells via administration of epitopes of Dsg 3 to induce immune tolerance to Dsg 3 in subjects (pg. 2, Solution of the task, para. 1-3). The specific epitopes of Dsg 3 taught by Eming are Seq ID 1-5, wherein Seq ID 2 of Eming is identical to instant SEQ ID NO: 1, Seq ID 3 of Eming is identical to instant SEQ ID NO: 2, and Seq ID 5 of Eming is a 17 amino acid sequence that contains a sequence with 95% identity with instant SEQ ID NO: 4 (pg., Solution of the task, para. 1, SEQUENCE LISTING of EP 2979704 A1, pg. 5 of English translation, and sequence search results below). The specific epitopes of Seq ID 1-5 were identified via T-cell proliferation assays and were found to have defined binding motifs for the human leukocyte antigen (HLA) class II alleles HLA-DRB1*04:02 and HLA-DQB1*05:03 (pg. 2, final para.).
SEQ ID NO: 1
BCM02440 standard; peptide; 15 AA.
DT 24-MAR-2016 (first entry)
DE Human desmoglein 3 (Dsg3) epitope peptide, SEQ ID 2.
CC PN EP2979704-A1.
CC PD 03-FEB-2016.
CC PI Eming R, Hertl M;
CC PS Claim 1; SEQ ID NO 2; 12pp; German.
SQ Sequence 15 AA;
Query Match 100.0%; Score 71; Length 15;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LNSKIAFKIVSQEPA 15
|||||||||||||||
Db 1 LNSKIAFKIVSQEPA 15
SEQ ID NO: 2
ID BCM02441 standard; peptide; 15 AA.
DT 24-MAR-2016 (first entry)
DE Human desmoglein 3 (Dsg3) epitope peptide, SEQ ID 3.
CC PN EP2979704-A1.
CC PD 03-FEB-2016.
CC PI Eming R, Hertl M;
CC PS Claim 1; SEQ ID NO 3; 12pp; German.
SQ Sequence 15 AA;
Query Match 100.0%; Score 76; Length 15;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPMFLLSRNTGEVRT 15
|||||||||||||||
Db 1 TPMFLLSRNTGEVRT 15
SEQ ID NO: 4
ID BCM02443 standard; peptide; 17 AA.
DT 24-MAR-2016 (first entry)
DE Human desmoglein 3 (Dsg3) epitope peptide, SEQ ID 5.
CC PN EP2979704-A1.
CC PD 03-FEB-2016.
CC PI Eming R, Hertl M;
CC PS Claim 1; SEQ ID NO 5; 12pp; German.
SQ Sequence 17 AA;
Query Match 94.7%; Score 71; Length 17;
Best Local Similarity 100.0%;
Matches 14; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 REGIAFRPASKTFT 14
||||||||||||||
Db 4 REGIAFRPASKTFT 17
The peptides of Seq ID 1-5 are taught to be coupled to suitable carriers, which in in some embodiments are taught to be nanoparticles (claims 1-2). In further embodiments, the nanoparticles may have an iron oxide or CdSe/CdS/ZnS core and have a coating that is an amphiphilic polymer such as poly(maleic anhydride-alt-1-octadecene) (pg. 3, final para. - pg. 4, para. 1). Eming additionally teaches the coupling of peptides to nanoparticles via a carbodiimide covalent bond and the coupling of a peptide or combination of peptides to appropriate nanoparticle carriers (pg. 4, para. 2). Finally, Eming teaches a method of treating Pemphigus vulgaris by inducing immune tolerance in PV patients via administration of Dsg 3 peptides (claims 5-7).
Eming does not teach a peptide comprising the sequence of SEQ ID NO: 3, a peptide comprising the sequence of SEQ ID NO: 4, the number average molecular weight (Mn) of the polymer comprising the nanoparticles, provide motivation for individually coupling peptides with nanoparticles, nor the diameter of the nanoparticles. These deficiencies are offset by the teachings of Veldman, Payne, Mohapatra, Herkel, and Wooster.
PNG
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216
690
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Greyscale
Veldman teaches a characterization of the specificity of T cell recognition of peptides from Desmoglein 3 in patients with Pemphigus vulgaris as compared to healthy patients (Abstract). The HLA class II alleles HLA-DRB1*0402 and DBR1*14/DQB1*0503 are taught to be involved in autoreactive T cells in PV patients and Veldman sought to identify Dsg 3 peptides that are recognized by autoreactive T helper cells in PV patients and to compare the peptide specificity in PV patients compared to healthy control patients (pg. 3883, right col., para. 2 - pg. 3884, left col., para. 1). The identified Dsg 3 peptides are shown in Table III (pg. 3887, reproduced below for convenience) and include DG3(189-205) which comprises instant SEQ ID NO: 1, DG3(205-221) which comprises instant SEQ ID NO: 2, DG3(250-266) which comprises 13/15 amino acids of instant SEQ ID NO: 3, and DG3(376-392) which comprises instant SEQ ID NO: 4.
All 8 of the peptide sequences listed in Table III were recognized by healthy and/or PV patients, with DG3(189-205) (instant SEQ ID NO: 1), DG3(205-221) (instant SEQ ID NO: 2), and DG3(250-266) (13/15 amino acids of instant SEQ ID NO: 3) being recognized by both and DG3(376-392) (instant SEQ ID NO: 4) being recognized only by PV patients (Figure 2A). These sequences correspond with regions of the extracellular domain of Desmoglein 3, with only sequences in EC1-3 domains being recognized by PV patients (Figure 2B).
Payne teaches compositions comprising one or more chimeric autoantibody receptor (CAAR) specific for an autoantibody, compositions comprising the CAARs, and methods of their use (Abstract and col. 2, lines 3-5). The CAARs of Payne’s invention are taught to target autoantibodies that can cause autoimmune diseases by targeting and killing pathogenic B cells (col. 13, line 41-67). Preferred embodiments include the “major pemphigus vulgaris autoantigen, desmoglein 3 (Dsg3) or fragments thereof” and the amino acid sequence of the extracellular (EC) domains 1-5 (amino acids 50-615 of Dsg3) are taught as SEQ ID NO: 3 (col. 14, lines 23-66). Additional sequences taught by Payne are SEQ ID NO: 5 which comprises EC1-3 domains of Dsg3 and SEQ ID NO: 7 which comprises EC2-3 domains of Dsg3 (col. 15, lines 4-12). Instant SEQ ID NO: 3 is a fragment of Dsg3 EC2, as shown below:
SEQ ID NO: 3
Patent No. 10301370
CURRENT FILING DATE: 2016-10-28
SEQ ID NO 7
LENGTH: 225
Query Match 100.0%; Score 81; Length 225;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NIKVKDVNDNFPMFR 15
|||||||||||||||
Db 96 NIKVKDVNDNFPMFR 110
Mohapatra teaches methods of detecting antigens in subjects utilizing multiple nanoparticles conjugated to different antibodies (Abstract and para. [0005]). By detecting antigens, determining levels of enzymatic products, and comparing to a reference, Mohapatra teaches that their methods can detect abnormal kidney function, such as various kidney diseases, and the presence of cancer (para. [0007-0008] and claims 29-31 and 45). Mohapatra further teaches multifunctionality in assays wherein a composition comprises two or more populations of nanoparticles with a different antibody conjugated to each nanoparticle, e.g., a composition with “a first antibody conjugated to a first nanoparticle” and “a second antibody conjugated to a second nanoparticle” (para. [0056-0058], Examples 1, 5, and 7, and claims 1, 17, 29, 43, and 45). The different nanoparticles are taught to have different cores, such as iron oxide, graphene oxide, or graphene oxide-silver, and different functionalization, such as thiolated gold or citric acid (para. [0059-0060] and claims 12-16, 25-28, and 39-42).
Herkel teaches pharmaceutical compositions comprising micellar nanoparticles made of amphiphilic polymers which have “a peptide comprising at least one T cell epitope associated with the outside of the micelle” and methods of generating regulatory T cells, preventing diseases and conditions, and treating diseases and conditions consisting of administering said compositions (Abstract). The micelle comprising amphiphilic polymers may have a solid hydrophobic core, preferably an inorganic core, which comprises iron oxide, CdSe, silver, or gold (para. [0012]).
Herkel teaches that the diameter of the nanoparticles is 30-100 nm with a core of 5-30 nm (para. [0006] and claim 5). In a preferred embodiment, the amphiphilic polymer forming the micelle is poly(maleic anhydride-alt-1-octadecene) (PMCH18) (para. [0010]). In another preferred embodiment, a nanoparticle comprising an iron oxide core coated with PMCH18 is taught to have a diameter of 9-12 nm (para. [0015]). The peptide is taught to preferably covalently linked to the outside of the micelles, “preferably covalently linked to the micelles, e.g., by carbodiimide or succinimide coupling” (para. [0017]). The peptide is taught to be 8-1,000 amino acids, preferably 9-60 amino acids or 10-20 amino acids, and to comprise “at least one T cell epitope” (para. [0018]).
Wooster teaches particles comprising conjugates of an active agent designed to deliver said active agent, methods of making the conjugates and particles, and methods of administering formulations containing the particles and conjugates to treat or prevent cancer or diseases (Abstract). The particles of Wooster’s invention may be polymeric nanoparticles, micelles of polymers and conjugates, or composition nanoparticles and the aforementioned conjugates may be encapsulated into the particles, embedded in the particle/medium interface, or “deposited on the surface of the particles” (para. [0007]). In an embodiment wherein the particles are polymeric, the polymers are taught to be hydrophobic, hydrophilic, or amphiphilic (para. [00149]). In the case that the polymers are amphiphilic, Wooster teaches that they may be copolymers of a hydrophobic polymer block and a hydrophilic polymer block, with one example of a hydrophobic polymer being poly(maleic acid) (para. [00168] and [00172]). In polymeric micellar nanoparticles made of amphiphilic polymers, the hydrophilic block is taught to comprise 40-70% w/w of the diblock copolymer and have a Mn of 500-20,000 daltons, while the hydrophobic block may be 30-60% w/w and have a Mn of 500-10,000 daltons, resulting in a total Mn range of 1,000-17,000 daltons (para. [00185]). This range of Mn is taught to be necessary because “[w]ithin this range, the micelle of the amphiphilic deblock copolymer can be maintained stably” (para. [00185]).
Wooster further teaches that their particles may comprise a solid, hydrophobic, inorganic core such as superparamagnetic nanoparticles of iron oxide, which are known as SPION (para. [00223]). The SPION cores are taught to be coated with inorganic materials such as silica or gold, with organic materials such as phospholipids or peptides, or with drugs, proteins, or plasmids (para. [00223]). In one embodiment, SPION cores are taught to be surrounded by oleic acid-poloxamer copolymers and the conjugate is linked to the exterior of the nanoparticle (para. [00224-00225]). The composition is further taught to comprise a stabilizing agent which may be mannitol (para. [00175]). Finally, Wooster teaches that the diameter of the nanoparticle should be 10-500 nm (claim 43) or “about 25 nm to about 250 nm” (para. [00150]).
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the number average molecular weights and nanoparticle diameters of the teachings of Herkel and Wooster. In each case, the ranges taught by Herkel and Wooster either encompass or significantly overlap with the ranges recited in instant claims 18, 20, 24, 30, and 43, resulting in a prima facie case of obviousness.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention of Eming with the teachings of Veldman, Payne, Mohapatra, Herkel, and Wooster to arrive at the invention of claims 1, 17-24, 26-32, 34-35, and 41 because combining prior art elements according to known methods to impart known benefits yields predictable results. Eming teaches use of peptides of Dsg 3 conjugated to nanoparticles in a medicinal preparation to treat Pemphigus vulgaris, wherein the nanoparticles may have solid inorganic cores of iron oxide or CdSe/CdS/ZnS and are coated with an amphiphilic polymer such as poly(maleic anhydride-alt-1-octadecene). In addition, Eming teaches the covalent coupling of the peptides of Dsg 3 to the exterior of the nanoparticles via carbodiimide chemistry and that the peptides may be individually conjugated to a nanoparticle or that multiple may be conjugated to a single nanoparticle. Finally, Eming teaches a method of inducing immune tolerance in PV patients via administration of Dsg 3 peptides.
In view of the teachings of Veldman, one of ordinary skill in the art would be motivated to use the identified Dsg 3 peptides in the invention of Eming because Veldman teaches the peptides to be recognized by the immune systems of PV patients. Eming teaches that peptides inducing an immune response are useful in treating PV and the ordinary artisan would recognize that two of the peptides taught by Eming are present in the peptides taught by Veldman. Similarly, a person of ordinary skill would be motivated to use SEQ ID NO: 5 taught by Payne because it comprises extracellular domains EC1-3 of Dsg 3, which is a fragment of Dsg 3 that comprises all of the amino acid sequences recognized by PV patients in the teachings of Veldman but not those sequences that were recognized in only healthy patients. An ordinary artisan would be motivated to use a peptide fragment that is known to trigger an immune response in PV patients rather than a sequence that only triggers the immune response of healthy patients and would also appreciate that the use of additional peptides that induce an immune response in PV patients would be beneficial in a medical preparation intended for such a response and would be motivated to incorporate the additional peptides.
Eming teaches that the nanoparticles of their invention may comprise a single peptide or more than one peptides of Dsg 3. In view of the teachings of Mohapatra, a person of ordinary skill would be motivated to individually conjugate peptides to individual nanoparticles because Mohapatra teaches this arrangement to provide multifunctionality. The ordinary artisan would recognize the benefit of multifunctionality in a composition that is utilizing multiple peptides to induce an immune response and would subsequently be motivated to coordinate individual peptides to individual populations of nanoparticles.
Eming is also silent regarding the diameter of the nanoparticles in their invention and the number average molecule weight (Mn) of the polymers used in their invention. In view of the teachings of Herkel, a person of ordinary skill would be motivated to optimize within the range of 30-100 nm because Herkel teaches this range of diameters to be appropriate for nanoparticles with inorganic cores comprising materials taught by Eming, coated with poly(maleic anhydride-alt-1-octadecene), and coupled to peptides. In addition, a person of ordinary skill would be motivated to use average molecular weight polymers in the range of 1,000-17,000 daltons in view of the teachings of Wooster because Wooster teaches this range is necessary to maintain a stable micelle made from amphiphilic copolymers. It would be obvious to an artisan use this Mn range because Eming is silent regarding the Mn of the polymers in their invention and one of ordinary skill would desire stable nanoparticles in their invention.
The references above do not explicitly state the number of types of nanoparticles in their inventions. However, the references above teach different materials may be used in the core of the nanoparticles and multiple amphiphilic polymers may coat the exterior of the nanoparticles. In addition, as evidenced by para. [0037] of the instant spec., each type of nanoparticle may be distinguished from the other by the peptide conjugated to the nanoparticle. Therefore, in view of the different materials and peptides rendered obvious above, more than four different types of nanoparticles would necessarily be present. MPEP § 2144.06 addresses the combination of equivalent compositions to address the same purpose. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The different Dsg 3 peptides taught above may interact with different HLA class II alleles in PV patients and the combination of the different nanoparticles to achieve multifunctional treatment of PV would be prima facie obvious to an ordinary artisan.
Finally, Herkel does not teach the method of measuring the diameter of their nanoparticles. However, the limitation recited in instant claim 24 is drawn to the diameter of the nanoparticle and not the method by which it was measured. Even though the process used by Herkel to measure the diameter of their nanoparticles is unknown and may be different from the method recited in instant claim 24, the diameter is prima facie obvious in view of the teachings of Herkel (vide supra) and the limitation is therefore met. As a result, there is a reasonable expectation of success in arriving at the invention of claims 1, 17-24, 26-32, 34-35, and 41 in view of the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Eming (European Patent Publication No. EP 2979704 A1, published on 3 February 2016, provided by Applicant in the IDS filed on 16 February 2024, references to English translation) in view of Veldman (J. Immunol. 2004, 172 (6), 3883.), Payne (U.S. Patent No. 10,301,370 B2, published on 28 May 2019), Mohapatra (U.S. Patent Application No. US 2020/0049700 A1, published on 13 February 2020), Herkel (European Patent Application Publication No. EP 2591801 A1, published on 15 May 2013), and Wooster (WIPO International Publication No. WO 2017/136652 A1, published on 10 August 2017) as applied to claims 1, 17-24, 26-32, 34-35, and 41-43 above, and further in view of Danaei et al. (Pharmaceutics 2018, 10 (2), 57., hereafter referred to as Danaei).
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster teach the above.
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster do not teach the polydispersity index of the nanoparticles in their compositions. This deficiency is offset by the teachings of Danaei.
Danaei teaches the impact of particle size and polydispersity index on lipidic nanocarrier systems (Abstract). The term polydispersity is taught to describe the degree of “non-uniformity of a size distribution of particles”, with smaller numbers corresponding to uniform particle sizes and larger values indicating “very broad particle size distribution” (pg. 8, para. 1-3). For drug delivery applications, while the FDA had not provided criteria for acceptable polydispersity indices in pharmaceutics, Danaei teaches that a polydispersity index of 0.3 and below is considered acceptable (pg. 8, final para.).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to formulate the invention rendered obvious by the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster to have nanoparticles with a polydispersity index of ≤0.3 in view of the teachings of Danaei because the use of a known technique in a given field to improve a product in the same field produces predictable results. The teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster rendered obvious a pharmaceutical composition comprising nanoparticles comprising inorganic cores of iron oxide or Cd/Se/CdS/ZnS and amphiphilic polymer coatings comprising poly(maleic acid-alt-1-octadecene), wherein different types of nanoparticles are individually conjugated via covalent bonds to peptides that comprise the amino acid sequences of SEQ ID NO:1-4. Further, the teachings of the references above rendered obvious the amphiphilic polymers having Mn values in the range of 1,000-17,000 g/mol and the nanoparticles having diameters in the range of 30-100 nm.
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster are silent on the polydispersity index of the nanoparticles of their inventions. In view of the teachings of Danaei, one of ordinary skill would be motivated to formulate the nanoparticles to have a polydispersity index of ≤0.3, which significantly overlaps with the range recited in instant claim 25, because Danaei teaches this range to be acceptable for pharmaceutical compositions. While the composition rendered obvious above does not comprise lipids, an ordinary artisan would recognize the applicability of the polydispersity index range in their composition because both the teachings of Danaei and the composition above are pharmaceutical compositions intended to be administered to patients. As a result, there is a reasonable expectation of success in arriving at the invention of claim 25 in view of the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster and further in view of the teachings of Danaei.
Claims 37-38 is rejected under 35 U.S.C. 103 as being unpatentable over Eming (European Patent Publication No. EP 2979704 A1, published on 3 February 2016, provided by Applicant in the IDS filed on 16 February 2024, references to English translation) in view of Veldman (J. Immunol. 2004, 172 (6), 3883.), Payne (U.S. Patent No. 10,301,370 B2, published on 28 May 2019), Mohapatra (U.S. Patent Application No. US 2020/0049700 A1, published on 13 February 2020), Herkel (European Patent Application Publication No. EP 2591801 A1, published on 15 May 2013), and Wooster (WIPO International Publication No. WO 2017/136652 A1, published on 10 August 2017) as applied to claims 1, 17-24, 26-32, 34-35, and 41-43 above, and further in view of Bevec (U.S. Patent Application Publication No. US 2010/0204131 A1, published on 12 August 2010).
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster teach the above.
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster do not teach the ratio of concentrations of nanoparticles in their compositions. This deficiency is offset by the teachings of Bevec.
Bevec teaches pharmaceutical compositions comprising a peptide sequence for the treatment of diseases (Abstract). Among the diseases Bevec teaches their composition may be used to treat are autoimmune disease, including Pemphigus vulgaris (para. [0029] and [0062]). When testing their peptides for activity in Examples 1-17, Bevec teaches that when more than one peptide is present, the peptides of their compositions should be used in equimolar amounts (para. [0256-0258]).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, in view of the teachings of Bevec to use nanoparticles conjugated to peptides in equimolar amounts in the invention rendered obvious by the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster because applying a known technique in a given field to a similar product in the same field in the same way yields predictable results. The teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster rendered obvious a pharmaceutical composition comprising nanoparticles comprising inorganic cores of iron oxide or Cd/Se/CdS/ZnS and amphiphilic polymer coatings comprising poly(maleic acid-alt-1-octadecene), wherein different types of nanoparticles are individually conjugated via covalent bonds to peptides that comprise the amino acid sequences of SEQ ID NO:1-4. Further, the teachings of the references above rendered obvious the amphiphilic polymers having Mn values in the range of 1,000-17,000 g/mol and the nanoparticles having diameters in the range of 30-100 nm.
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster are silent regarding the ratio of peptides and/or nanoparticles in their inventions. In view of the teachings of Bevec, a person of ordinary skill would be motivated to use equimolar amounts of nanoparticles to provide equimolar amounts of peptides because Bevec teaches this ratio to be appropriate in pharmaceutical compositions comprising more than one peptide for the treatment of autoimmune diseases, including Pemphigus vulgaris. In addition, the teachings of Bevec regarding concentration ratios provides missing information that an ordinary artisan would need to complete their invention. As a result, there is a reasonable expectation of success in arriving at the invention of claims 37-38 in view of the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster and further in view of the teachings of Bevec.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Eming (European Patent Publication No. EP 2979704 A1, published on 3 February 2016, provided by Applicant in the IDS filed on 16 February 2024, references to English translation) in view of Veldman (J. Immunol. 2004, 172 (6), 3883.), Payne (U.S. Patent No. 10,301,370 B2, published on 28 May 2019), Mohapatra (U.S. Patent Application No. US 2020/0049700 A1, published on 13 February 2020), Herkel (European Patent Application Publication No. EP 2591801 A1, published on 15 May 2013), and Wooster (WIPO International Publication No. WO 2017/136652 A1, published on 10 August 2017) as applied to claims 1, 17-24, 26-32, 34-35, and 41-43 above, and further in view of Bhattacharjee et al. (U.S. Patent Publication No. 2020/0276274 A1, published on 3 September 2020, hereafter referred to as Bhattacharjee) and Abd Alsaheb et al. (J. Chem. Pharm. Res. 2015, 7 (10), 729., hereafter referred to as Abd Alsaheb).
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster teach the above.
Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster do not teach their compositions to comprise D-mannitol, Tris, and L-lactic acid. These deficiencies are offset by the teachings of Bhattacharjee and Abd Alsaheb.
Bhattacharjee teaches pharmaceutical compositions comprising a peptide for treating diabetes and diabetes-related disorders (Abstract). To maintain stability in the pharmaceutical composition, Bhattacharjee teaches the inclusion of excipients including anti-microbial agents, a buffer, an antioxidant, a tonicity agent, and pH adjusting agents (para. [0017-0021]). In some embodiments, the preferred tonicity agent is a sugar such as mannitol (para. [0060] and claims 4, 11, and 17) and the preferred buffer is tri(hydroxymethyl)aminomethane (TRIS or THAM) (para. [0058] and claims 4, 11, and 17).
Abd Alsaheb teaches a review of the pharmaceutical and cosmeceutical applications of lactic acid (Abstract). The L(+) isomer is taught to be appropriate for use because the D(-) isomer is not metabolized by the human body (pg. 731, 1. Pharmaceutical Applications of lactic acid). Lactic acid is taught to be capable of functioning as an electrolyte and pH adjustment agent in compositions that are parenterally or intravenously administered (pg. 731, 1.1 parenteral/I.V) and to be well tolerated by the human body (pg. 732, 1.3 Controlled drug delivery system and 1.5. Mineral lactate formulations for diseases).
It would have been prima facie obvious to one of ordinary skill in the art prior to the filing of the instant application to combine the teachings of Bhattacharjee and Abd Alsaheb with the invention rendered obvious by the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster because combining prior art elements according to known methods to impart known benefits yields predictable results. The teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster rendered obvious a pharmaceutical composition comprising nanoparticles comprising inorganic cores of iron oxide or Cd/Se/CdS/ZnS and amphiphilic polymer coatings comprising poly(maleic acid-alt-1-octadecene), wherein different types of nanoparticles are individually conjugated via covalent bonds to peptides that comprise the amino acid sequences of SEQ ID NO:1-4. Further, the teachings of the references above rendered obvious the amphiphilic polymers having Mn values in the range of 1,000-17,000 g/mol and the nanoparticles having diameters in the range of 30-100 nm.
One of ordinary skill in the art would be motivated to use TRIS as a buffer and mannitol as a tonicity agent in the composition rendered obvious above because Bhattacharjee teaches the components to be compatible with compositions comprising peptides and to provide stable pharmaceutical compositions, which the ordinary artisan would recognize as desirable. In view of the teachings of Abd Alsaheb, a person of ordinary skill would be motivated to include lactic acid in the composition rendered obvious above because Abd Alsaheb teaches the organic acid to be well tolerated by the human body and to be multifunctional, including acting as an electrolyte and pH adjustment agent. An ordinary artisan would recognize the utility of these functions and desire their pharmaceutical composition to be well tolerated by subjects. As a result, there is a reasonable expectation of success in arriving at the invention of claim 40 in view of the teachings of Eming, Veldman, Payne, Mohapatra, Herkel, and Wooster and further in view of the teachings of Bhattacharjee and Abd Alsaheb.
Allowable Subject Matter
Claims 33, 36, and 39 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Specifically, claim 33 recites the amino acid sequences linked to the third and fourth type of nanoparticles to consist of SEQ ID NO: 3 and 4, respectively. These specific 15 amino acid sequences are free of the prior art. Claims 36 and 39 depend from claim 33 and would therefore also be allowable if claim 33 were rewritten in independent form.
Conclusion
Claims 1, 17-32, 34-35, 37-38, and 40-41 are rejected.
Claims 33, 36, and 39 stand objected.
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/S.J.S./
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
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