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 .
The Response of 5 Feb. 2025 has been entered.
Claims 1-11, 13-15 and 18-21 are pending and are considered here.
Response to Arguments
Applicant's arguments filed 5 Feb. 2025 have been fully considered but they are not persuasive.
Applicant argues that Xia and Tang fail to teach a peptide length of at least 15 amino acids. This is not persuasive because the term “peptide” is defined in the instant specification to include proteins such as Con A (see modified 103 rejection, below).
Applicant further argues that claims 8-10 are distinguishable from the cited combination of Xia in view of Tang and Boschetti because Boschetti teaches that, for peptides beyond 4 amino acids in length, a plateau is reached in the number of captured proteins and one of ordinary skill would thus be discouraged from testing peptides longer than the hexapeptides exemplified by Boschetti. This is not persuasive because a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage the claimed modification (see MPEP 2145, X., D.). While Boschetti teaches that the total number of captured proteins in one study tended towards a plateau at lengths greater than 4 amino acids, Boschetti further teaches that the composition of bound proteins changes with increasing length towards smaller peptides/proteins and expressly suggests that longer peptides could be used to improve capture of shorter and/or rare proteins/peptides (see modified 103 rejection, below). One of ordinary skill could further be motivated to experiment with longer peptides in order to capture specific post-translational modifications, such as glycoproteins, using a library constructed around a PTM-binding consensus sequence, as suggested by Boschetti. Thus, Boschetti does not generally criticize, discredit or otherwise discourage the use of longer peptides but rather merely states that increasing length does not yield large gains in the total number of captured proteins.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63181765, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In particular, the priority application does not provide adequate written description support for a system having the combination of properties set forth in claim 1, including a surface with a peptide with at least three different proteins bound to the peptide and at least about 10 different proteins adsorbed to the surface and not bound to the peptide. The effective date for the instant claims is thus the PCT filing date of 29 April 2022.
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.
Claims 8, 9 and 21 are rejected under 35 U.S.C. 112(b) 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.
Claims 8 and 9 recite “about 40 amino acids” (claim 8) and “about 20 amino acids” (claim 9). The term “about” which is a relative term which renders the claim indefinite (it is unclear how many additional/less amino acids than the number recited would fall within the scope of “about”). The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 21 recites that “a plurality of biomolecules is increased in visibility in a downstream assay, wherein visibility is measurable by an increase in intensity as measured by mass spectrometry”. The meaning of the term “increased in visibility” is unclear, as the term “increased” is a relative term for which a standard/reference value has not been specified (i.e. it is unclear what comparison would be involved in ascertaining whether any particular set of biomolecules is “increased in visibility”).
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 1-7, 10, 11, 13-15 and 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020096631 to Xia et al. (cited in IDS of 8 May 2024) in view of Tang et al., Proteomics 10.10 (2010): 2000-2014, as evidenced by Bøg‐Hansen et al., Scandinavian Journal of Immunology 4 (1975): 135-139 and Bouckaert et al., Proteins: Structure, Function, and Bioinformatics 23.4 (1995): 510-524..
Regarding claim 1, Xia teaches a system for analyzing protein coronas for proteomics analysis, the system comprising a nanoparticle (a surface) to which a plurality of biomolecules/proteins are adsorbed wherein the surface is functionalized with a peptide/protein designed to bind specific types/subsets of proteins (i.e. having a binding site) that can be analyzed as part of the protein corona of bound biomolecules that forms on the particle (entire doc, including [0003]-[0050]; [0101]-[0130]). The different subsets can include proteins having a particular post-translational modification ([0141]). The nanoparticles can be used for proteomics analyses, including identification of proteins in the corona via mass spectrometry (e.g., [0105]).
Claim 1 differs from Xia in that: at least three different proteins are bound to the peptide binding site; and the peptide coupled to the surface comprises at least 15 amino acids.
Tang teaches peptide-functionalized nanoparticles for proteomics analysis of the type taught by Xia wherein the particles are functionalized with the lectin Concanavalin A (Con A), which specifically binds sugar epitopes of glycopeptides (entire doc, including under 1 Introduction). Tang teaches that approximately half of all proteins are glycoproteins and that glycoproteins undergo changes in quality and quantity in different physiological and pathological states, making them potential targets for diagnostic analyses (under 1. Introduction). Bog-Hansen further evidences that each Con A has four binding sites for glycosylated residues (Bog-Hansen, p. 135, 2nd ¶).
Regarding the recitation in claim 1 that the peptide coupled to the surface comprises at least 15 amino acids, the instant specification defines “peptide” to include proteins (Published Spec. US20240219400, [0269]). Bouckaert evidences that Con A comprises more than 15 amino acids (237 amino acids) (Bouckaert, 1st ¶ under INTRODUCTION).
Regarding the recitation in claim 1 that the plurality of biomolecules adsorbed on the surface comprises at least about 10 proteins not specifically bound to the peptide, Xia teaches that it is desirable for proteomics profiling applications to detect the widest possible number of proteins including a wide dynamic range of proteins (including proteins present at varying concentrations in the sample, such as rare isoforms/species), and that this can be accomplished by using multiple particles (a panel) having a diversity of different surface chemistries/properties that result in the formation of distinct protein coronas on each particle [0098]-[0150]). Xia further teaches that the particles/panel can be designed to detect specific subsets of proteins ([0117), and that the particles in a panel can each have one or more surface properties in common and one or more different other surface properties ([0118]). In light of the above, one of ordinary skill would have been motivated to prepare particles functionalized with Con A as taught by Tang in order to assay glycoproteins wherein the particles are further designed with a surface chemistry that adsorbs different types/subsets of glycoproteins (i.e. a plurality of biomolecules) to each particle. Regarding the recitation of at least 10 different proteins being adsorbed to the surface, Xia teaches that it is desirable to maximize the number of different bound proteins in the corona and teaches that a single particle of a panel can be capable of producing a corona of 600 different proteins ([0143]). Thus, it would have been obvious to one of ordinary skill to configure the particles to adsorb at least 10 different proteins on the surface with a reasonable expectation of success.
Regarding the recitation in claims 1, 2 and 4 that at least three or four different proteins are bound to Con A on the particle, Tang teaches that about half of all proteins are glycoproteins and Xia teaches that it is desirable to maximize the number of different bound proteins and that a single particle can include about 600 different bound proteins. In light of the above, it would have been obvious to configure the particle and assay conditions such that the particle has at least three or four different proteins bound to Con A with a reasonable expectation of success.
Regarding the recitation in claim 3 that the three different protein are bound to a single instant of Con A, Bog-Hansen evidences that Con A has binding sites for 4 glycoproteins and Xia teaches that it is desirable to maximize the number of different bound proteins and to capture rare proteins/isoforms. In light of the above, it would have been obvious to configure the particle and assay conditions such that a single ConA has at least three different bound proteins (e.g., wherein the particle is configured with a combination of Con A and a surface chemistry designed to capture rare proteins, one would have a reasonable expectation of success in aiming to maximize the diversity of proteins detected (and considering stochastic aspects of protein binding interactions at a large number of individual Con A sites) to arrive at a particle with three different proteins at a single ConA site).
Regarding claims 5 and 6, the cited combination makes obvious a particle with three different proteins at a single Con A binding site and as such the amount of each would be within one magnitude of each other. It is noted that “the peptide” is construed herein to include a single instance of the peptide in light of claim 3 which further limits “the peptide” in claim 1 to include a single instance.
Regarding claim 7, Xia teaches that a combination of surface properties (e.g., a peptide functionalization such as Con A common to all particles in a panel along with varying surface charge or other property to capture different groups of glycoproteins) can be used to enrich certain subsets of proteins from a sample (see above), and it would have been obvious in view of this vary the density of Con A on the particles using routine optimization to achieve a density low enough to allow for protein interaction with the particle surface to in turn vary the diversity and/or composition of the resulting coronas among particles in the panel (see MPEP 2144.05).
Regarding claim 10, it would have been obvious that the Con A used in the method could be a recombinant sequence and/or could include any accessory sequences (e.g., His Tags or the like) to facilitate expression or purification (which can be considered “synthetic sequences”).
Regarding claim 11, Xia teaches that the surface-bound peptide can include non-natural amino acids in order to introduce diverse chemistry/functionality ([0128]).
Regarding claims 13 and 15, Tang teaches that Con A specifically binds a particular epitope on glycosylated proteins and thus the different bounds proteins would comprise such epitope and be specifically bound to Con A.
Regarding claim 14, Xia teaches that it is desirable to configure the particles and assay to capture and identify rare proteins and isoforms, and as such it would have been obvious to carry out the assay so as to capture two or more proteoforms/isoforms of the same glycoprotein.
Regarding claim 18, Xia teaches that it is desirable to maximize the dynamic range of the assay and states that the dynamic range of bound proteins can be at least 5 ([0140]).
Regarding claim 19, Xia teaches that the surface area of the particles is one of the properties that can be varied in a particle panel ([0136]), and as such it would have been obvious to vary the surface area for any given volume in the assay using routine experimentation in order to vary the diversity and/or composition of the resulting corona.
Regarding claim 20, Xia teaches that the particles within the panel can vary among multiple dimensions, e.g. having a Con A surface functionalization that would selectively bind glycoproteins from a sample along with a surface charge would selectively bind a subset of other proteins from the sample. By providing multiple bases for selectively binding proteins from a sample, it would have been obvious to produce a particle wherein at least two bound proteins within the corona are captured at a ratio different from that present in the sample (which would occur any time the selection ratio for two different surface properties is non-identical).
Regarding claim 21, Xia teaches that the particles can be used to selectively enrich certain proteins in a protein corona (plurality of biomolecules) and that the corona can be assayed, e.g. via MS, such that the bound proteins have “increased visibility” in a downstream assay.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Xia in view of Tang as evidenced by Bøg‐Hansen and Bouckaert, as applied to claims 1-7, 10, 11, 13-15 and 18-21, further in view of Boschetti et al., Proteomics 9.6 (2009): 1492-1510.
Claims 8-10 differ from the combination of Xia in view of Tang as evidenced by Bøg‐Hansen and Bouckaert, as applied to claims 1-7, 10, 11, 13-15 and 18-21, in that: the peptide comprises 40 or less amino acids (claim 8); the peptide comprises 20-40 amino acids (claim 9); the peptide comprises a synthetic sequence (claim 10).
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). Boschetti also envisions the development of specialized libraries for the capture of specific post-translational modifications (PTM), such as glycoproteins, built around a PTM-binding consensus sequence (p. 1507, right col., 2nd ¶).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to prepare peptide functionalized nanoparticles for corona analysis as taught by Xia in view of Tang wherein the particles include a peptide from a synthetic peptide library as taught by Boschetti 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 a synthetic peptide as taught by Boschetti in the particle of Xia in view of Tang in order to further tailor the surface properties to capture a desired subset of proteins, such as rare and/or or small proteins. Using a synthetic peptide as taught by Boschetti in the particle of Xia in view of Tang would have led to predictable results with a reasonable expectation of success because Boschetti teaches that such peptides are useful for a substantially similar purpose as the peptide of Xia in view of Tang.
Regarding the recitation in claims 8-9 that the peptide is 20-40 amino acids in length, 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 peptides).
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657