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 .
Claims 1-23 are currently pending and are considered here.
Claim Objections
Claim 7 is objected to because of the following informalities:
Claim 7 should be amended as follows: “… wherein at least one of the at least two distinct particle types comprises a surface bound peptide …”.
Appropriate correction 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.
Claims 1-12 and 14-23 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of US20180172694 to Farokhzad et al. in view of US20120046184 to Dawson et al. and Boschetti et al., Proteomics 9.6 (2009): 1492-1510.
Regarding claim 1, Farokhzad teaches a system for enriching proteins from a sample comprising: at least two distinct particle types each having different physiochemical properties such that each particle is capable of binding a different set of proteins from a complex sample, wherein upon exposure to a complex sample each of the at least two distinct particle types forms a corona comprising a plurality of biomolecules from the sample adsorbed on its surface ([0008]-[0027]; [0157]-[0186]; [0200]-[0219]; [0241]-[0254]; Examples 1-7). The unique subset of biomolecules within each particle corona forms a signature, and the group of signatures from the multiple particles of the system provides a fingerprint for the sample that is capable of distinguishing/diagnosing disease states in a subject ([0008]-[0027]; [0241]-[0254]). Farokhzad further teaches that the surfaces of the particles can functionalized with various chemical moieties (e.g., amine, carboxyl, etc.; polymers such as PEG, methacrylic acid, etc.) to provide different physiochemical properties ([0121]-[0128]; [0200]-[0205]; Examples 4-5; claim 26).
Regarding the recitation in claim 1 that the plurality of adsorbed biomolecules comprises at least 100 proteins, Farokhzad provides examples in which a system comprising three different nanoparticles were contacted with a plasma sample and each nanoparticle was found to have at least 500 proteins within the corona (Fig. 10B; Examples 1-2).
Regarding claim 8, Farokhzad teaches that the particles can comprise magnetic particles ([0215]; Example 2).
Regarding claims 9-10, Farokhzad teaches that the particles can comprise iron oxide nanoparticles, including superparamagnetic iron oxide nanoparticles ([0179]; [0204]; Example 2)
Regarding claim 11, Farokhzad teaches that the particles can comprise a polymer, e.g. a PEG coating ([0204]-[0205]; [0213]-[0219]; Example 2)
Regarding claims 12 and 14, Farokhzad teaches a system comprising particles comprised of superparamagnetic iron oxide nanoparticle, gold and a polymer (Example 2 - comprising a superparamagnetic iron oxide nanoparticle with a polymeric (PEG) coating and gold nanoparticles).
Regarding claims 15-16, Farokhzad teaches that the particles can range in size between 100 nm and 500 nm ([0164]).
Regarding claims 17-18, Farokhzad teaches a system comprising multiple particles having a surface zeta potential of between -15 to -25 (Example 4; Fig. 45A).
Regarding claim 19, Farokhzad teaches that the plurality of particles (sensor elements) can include up to 1000 particles ([0165]-[0166]), and exemplifies systems comprising at least three distinct particles (Example 1A (3 particles); Example 2 (12 particles); Example 4 (6 particles)).
Claims 1-12 and 14-23 differ from Farokhzad in that: each particle comprises a surface bound peptide having binding specificity for a different set of proteins of the sample, wherein each peptide comprises at most 40 amino acids and has a different isoelectric point (claim 1); each peptide comprises 5-40 amino acids (claim 2), 15-30 amino acids (claim 3) and 20-25 amino acids (claim 4); at least one peptide has an isoelectric point between 4 and 10 (claim 5), between 4 and 7 (claim 6) and between 5 and 10 (claim 7); the system comprises at least 3 distinct particles wherein the third of the at least three distinct particle types comprise a surface bound peptide having an isoelectric point that is different from the peptide of the first or the second distinct particle type (claim 20); and at least one of the particles comprises the surface bound peptide at a density of at least 1 peptide per 200 nm2 (claim 21), at least 1 peptide per 50 nm2 (claim 22) and at least 1 peptide per 5 nm2 (claim 23).
Dawson teaches systems and methods for enriching proteins from a sample using a substantially similar approach as in Farokhzad, comprising combining a collection of multiple nanoparticles having distinct physiochemical properties with the sample so as to form unique biomolecule/protein coronas on the surface of the particles ([0005]-[0023]; [0028]-[0040]; [0088]-[0105]). One or more physiochemical properties of the nanoparticle surfaces can be selectively modified to capture different biomolecules/proteins from the sample, including surface charge, surface chemistry and/or surface functionalization ([0013]-[0014]; [0028]-[0030]). The surface functionalization can be with a ligand, such as an oligopeptide; e.g., an RGD peptide ([0029]; [0076]; [0115]-[0117]; Fig. 17). Dawson teaches that the peptide-functionalization combines with other surface properties (wherein proteins bind to the particle surface, and also to the peptide) to provide additional specificity to each nanoparticle ([0116]-[0117]).
Boschetti teaches the use of synthetic peptides as capture reagents for various subsets of proteins, and the use of such peptides to identify rare protein species for proteomics applications (entire doc, including under 4. Focus on peptide libraries). Boschetti further teaches that varying the length of the peptide can vary the size and composition of the pool of captured proteins (with increasing size resulting in increasing numbers of captured proteins and increased numbers of smaller sized peptides/proteins) (p. 1500, 1st para). Boschetti further teaches that in the future "it is envisioned that peptide libraries will be improved in their length in order to better capture/concentrate proteins of low mass values" (p. 1507, 4th ¶), and that "use of more, or even less, amino acids, including unnatural ones, would probably be one way to improve the efficacy of libraries in order to both reduce the risk of undetecting known proteins and to enhance the detection of very low-abundance species that escape the capture phenomenon. In this respects peptides of different length (shorter or even longer chains) are very possible extensions" (p. 1507, last ¶ under 5 Future: forecast versus prospective).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to prepare a system comprising a plurality of surface-functionalized nanoparticles for corona analysis each having distinct physiochemical properties as taught by Farokhzad wherein the surface functionalization comprises a peptide as taught by Dawson because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to functionalize the surfaces of the particles with peptides because Dawson teaches that peptide-functionalization combines with other surface properties to provide additional specificity to each nanoparticle. Functionalizing the surfaces of the particles with peptides as taught by Dawson would have led to predictable results with a reasonable expectation of success because Farokhzad teaches that the particle surfaces can be functionalized with a variety of functional groups in the form of a polymer, and Dawson teaches that peptide functionalization is useful for the same general purpose of varying the physiochemical properties of particles for protein enrichment and corona analysis as taught by Farokhzad.
Regarding the recitation in claim 1 that each peptide has binding specificity for a different set of proteins of the sample, Dawson teaches use of an RGD peptide which has binding specificity for integrin receptors (Dawson, [0116]) and Boschetti teaches peptides useful for targeting specific proteins, e.g. the plasma protein von Willebrand factor (Boschetti, Table 2). Farokhzad further teaches that the “type, amount, and categories of the biomolecules that make up these biomolecule corona are strongly related to the physicochemical properties of the sensor elements themselves and the complex interactions between the different biomolecules themselves and the sensor elements. These interactions lead to the production of a unique biomolecule corona signature for each sensor element” (Farokhzad, [0160]). Since Farokhzad teaches that it is advantageous to include particles with a wide range of physiochemical properties and binding affinities to maximize the number of different biomolecule signatures (e.g., to facilitate detection of rare proteins), it would have been obvious to include particles functionalized with a wide range of peptides including those with unique binding specificities as taught by Dawson and Boschetti (as taught by Farokhzad, the binding of proteins to the peptide along with binding interactions between the peptide-bound proteins and additional biomolecules would yield unique corona signatures for each of the peptides taught by Dawson and Boschetti).
Regarding the recitation in claim 1 that each peptide comprises at most 40 amino acids and the recitation in claim 2 that each peptide comprises 5-40 amino acids, Dawson teaches use of a tripeptide (RGD) and Boschetti provides examples of specific affinity peptides ranging in size from 3-11 amino acids (Table 2) as well combinatorial hexapeptide libraries (Table 3). It would have thus been obvious to use peptides within the claimed ranges. Regarding the ranges of 15-30 amino acids and 20-25 amino acids in claims 3-4, Boschetti teaches that peptide length is a result-effective variable and it would have thus been obvious to vary the length of the peptide using routine optimization to produce a desired binding profile and corona formation (e.g., to enhance capture of small, rare and/or specifically modified proteins) (see MPEP 2144.05).
Regarding the recitation in claims 1 and 20 that each peptide has a different isoelectric point (Pi), Farokhzad and Dawson teach using particles having a range of distinct physiochemical surface properties, including different binding moieties and surface charges (e.g., Farokhzad, [0201]-[0205], Examples; Dawson, Example 1A, Fig. 4). One of ordinary skill in the art would have thus been motivated to use peptides having distinct sequences and net charges (leading to different Pi values) in order to provide for different biomolecule signatures on each particle.
Regarding the Pi values recited in clams 5-7, the Pi of any peptide is a function of the sequence and can be predicted with, e.g. the Expasy - Compute pI/Mw tool at web.expasy.org/compute_pi/. The RGD peptide exemplified by Dawson has a Pi of 5.8, and Boschetti teaches peptides having Pi values ranging from 4 (YNFEVL, Table 2) to 10 (KLRSFY, Table 3). Farokhzad and Dawson teach using a large number of distinct particles (e.g., up to 1000) having a wide variation of surface physiochemical properties in order to obtain unique signatures/fingerprints and detect rare proteins, and as such it would have been obvious to use peptides having a variety of sequences and Pi values including those within the claimed ranges.
Regarding claims 21-23, Dawson teaches that controlling both surface charge and surface charge density of nanoparticles can vary the protein coronas/signatures (Dawson, Example 1A). Dawson thus teaches that the density of charged functional groups (e.g., provided via peptide functionalization) is a result-effective variable for protein corona formation, and as such it would have been obvious to use routine optimization to vary the peptide density to give desired binding characteristics to the particles (see MPEP 2144.05).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Farokhzad in view of Dawson and Boschetti, as applied to claims 1-12 and 14-23, further in view of Sakulkhu et al., Biomaterials science 3.2 (2015): 265-278.
The teachings of Farokhzad in view of Dawson and Boschetti are set forth above. Regarding claim 13, Farokhzad teaches use of core-shell particles and exemplifies use of superparamagnetic iron oxide nanoparticles with a polymer shell as well as gold nanoparticles (i.e. gold surface) (Farokhzad, Example 2)
Claim 13 differs from the combination of Farokhzad in view of Dawson and Boschetti, as applied to claims 1-12 and 14-23, in that: the at least two distinct particle types comprise a core comprising a superparamagnetic iron oxide nanoparticle (SPION), a shell comprising a polymer, and shell comprising gold.
Sakulkhu teaches nanoparticles comprising a superparamagnetic iron oxide core with a shell comprised of a polymer (various forms of PVA) or gold, and measures the protein coronas formed on such nanoparticles upon exposure to serum (entire doc, including Abstract). The gold-coated and polymer-coated nanoparticles were found to have distinct coronas, and Sakulkhu teaches that the nature of the shell material has a significant effect on the composition of the coronas formed (Tables 3-5; p. 276, under Conclusions).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to prepare a system comprising a plurality of peptide-functionalized nanoparticles for corona analysis each having distinct physiochemical properties as taught by Farokhzad in view of Dawson and Boschetti wherein the particles include SPION particles having a polymeric shell and SPION particles having a gold shell as taught by Sakulkhu because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use SPION particles having a polymeric shell and a gold shell because Farokhzad and Dawson teach that it is desirable to use particles having a wide range of physiochemical properties so as to form unique protein corona signatures, and Sakulkhu teaches that the shell material (including gold vs. organic polymer) significantly varies the composition of coronas formed on the particles. Using SPIONs with a polymeric shell and a gold shell in the method of Farokhzad in view of Dawson and Boschetti would have led to predictable results with a reasonable expectation of success because Farokhzad teaches use of core-shell particles, as well as particles with a SPION core and particles with polymeric and gold surfaces.
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 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11567086 in view of Farokhzad, Dawson, Boschetti and/or Sakulkhu, as applied in the 103 rejection above. The claims of the ‘086 patent teach a system comprising a plurality of nanoparticles each differing in at least one physiochemical property and capable of forming a unique biomolecule corona upon exposure to a biological fluid such as plasma (‘086, claims 1, 15, 19). The ‘086 claims further teach that the nanoparticles can comprise a superparamagnetic core (‘086, claim 16) and can comprise a metal such as gold and/or a polymer (‘086, claims 2, 14). The ‘086 claims do not teach functionalization of the particles with a peptide as in the instant claims. However, Farokhzad teaches a substantially similar nanoparticle system for the same purpose of protein corona formation/analysis wherein the physiochemical properties of the particles can be varied via surface functionalization (e.g., with a polymer), and Dawson teaches peptide functionalized nanoparticles in a substantially similar protein corona-forming system (see above). Moreover, Farokhzad, Dawson, Boschetti and/or Sakulkhu teach and/or render obvious each of the dependent limitations in the context of the claimed system (see 103 rejection, above).
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12000827 in view of Farokhzad, Dawson, Boschetti and/or Sakulkhu, as applied in the 103 rejection above. The claims of the ‘827 patent teach a system comprising a plurality of particles each differing in at least one physiochemical property and capable of forming a unique biomolecule corona upon exposure to a biological fluid such as plasma (‘827, claims 1, 18). The ‘827 claims further teach that the different physiochemical properties can include different surface zeta potentials (‘827, claims 15 and 16). The ‘827 claims do not teach functionalization of the particles with a peptide as in the instant claims. However, Farokhzad teaches a substantially similar nanoparticle system for the same purpose of protein corona formation/analysis wherein the physiochemical properties of the particles can be varied via surface functionalization (e.g., with a polymer), and Dawson teaches peptide functionalized nanoparticles in a substantially similar protein corona-forming system (see above). Moreover, Farokhzad, Dawson, Boschetti and/or Sakulkhu teach and/or render obvious each of the dependent limitations in the context of the claimed system (see 103 rejection, above).
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12228566 in view of Farokhzad, Dawson, Boschetti and/or Sakulkhu, as applied in the 103 rejection above. The claims of the ‘566 patent teach a system comprising a plurality of magnetic nanoparticles each differing in at least one physiochemical property and capable of forming a unique biomolecule corona upon exposure to a biological fluid (‘566, claim 1). The ‘566 claims further teach that the particles can vary in size (‘566, claims 11-15), that the particles can be surface-functionalized, e.g. with a carboxylate or ammonium group (‘566, claims 16-18) and that the particles can comprise iron oxide (‘566, claim 19). The ‘566 claims do not teach functionalization of the particles with a peptide as in the instant claims. However, Dawson teaches nanoparticles in a substantially similar protein corona-forming system wherein peptide functionalization is used to alter the physiochemical/binding properties of the particles (see above). Moreover, Farokhzad, Dawson, Boschetti and/or Sakulkhu teach and/or render obvious each of the dependent limitations in the context of the claimed system (see 103 rejection, above).
Conclusion
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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