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 .
DETAILED ACTION
Summary
This is a Final Office action based on the 18/006142 response filed on 03/04/2026.
Claims 205-213, 216-220 & 224 are pending and have been fully considered.
Claims 1-204, 214-215, 221-223 are cancelled
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 205-213, 216-220 & 224 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-60 of co-pending Application No. 18/547831 in view of FAROKHZAD in view of DAWSON as shown below.
18/547831 claims a method of selecting surfaces for a biomolecule assay, comprising: (a) providing one or more biological samples comprising a plurality of biomolecules; (b) contacting the one or more biological samples with a plurality of surfaces, such that each surface in the plurality of surfaces adsorbs a subset of biomolecules in the plurality of biomolecules; (c) determining, for each surface in the plurality of surfaces, abundances of the subset of biomolecules adsorbed thereon; and (d) selecting a subset of surfaces in the plurality of surfaces based at least in part on the abundances when the subset of surfaces adsorbs biomolecules or biomolecule groups that comprise a different abundance pattern compared to another subset of surfaces in the plurality of surfaces.
18/547831 does not teach that only .1% by mass of proteins are absorbed or the claimed surface area to mass ratio of the comparison to a substrate that is 10 % or more greater, however there are 112 issues with these things as shown below and further, FAROKHZAD in view of DAWSON teach this as shown below. It would have been obvious to one of ordinary skill in the art at the time of invention to detect lowly abundance proteins as is done in DAWSON and one would have had reasonable expectation of success to combine with FAROKHZAD due to the need in the art for better methods/systems for detection of complex protein mixtures (DAWSON, paragraph 0002).
Claims 205-213, 216-220 & 224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-28 of copending Application No. 17/099331 in view of FAROKHZAD in view of DAWSON as shown below.
17/099331 claims a method for assaying a biological sample, comprising: (a) contacting the biological sample with a plurality of particles comprising different particle types to permit biomolecules of the biological sample to bind to the plurality of particles and form coronas around the plurality of particles, wherein the coronas corresponding to the different of particle types (i) differ based on particle type, and (ii) comprise overlapping and distinct proteins; (b) separating at least a subset of the plurality of particles comprising the coronas from the biological sample by removing the subset of the plurality of particles thereby producing a subset of proteins from the biological sample; (c) assaying the subset of proteins of (b) with an instrument to detect, in the subset, proteins in the biological sample at concentrations across a broad dynamic range, thereby assaying the biological sample.
17/099331 does not teach that only .1% by mass of proteins are absorbed or the claimed surface area to mass ratio of the comparison to a substrate that is 10 % or more greater, however there are 112 issues with these things as shown below and further, however FAROKHZAD in view of DAWSON teach this as shown below.
It would have been obvious to one of ordinary skill in the art at the time of invention to detect lowly abundance proteins as is done in DAWSON and one would have had reasonable expectation of success to combine with FAROKHZAD due to the need in the art for better methods/systems for detection of complex protein mixtures (DAWSON, paragraph 0002).
These are provisional nonstatutory double patenting rejections.
Claim Objections
Claim 205 is objected to because of the following informalities:
With respect to Claim 205, the preamble is drawn towards “identifying,” which could be interpreted as a mental process/abstract idea. However, the claim body, makes it clear that the claimed identifying is meant to be “assaying…by mass spectrometry,…thereby identifying.” This makes it reasonably clear that the claimed identification and assaying is by performing mass spectrometry detecting, and that what is being claimed is not an abstract idea. It would be clearer if state that measuring or detecting by mass spectrometry is performed in the claim body. It further would be clearer if this was also reflected in the claim preamble. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 205-213, 216-220 & 224 and those that depend therefrom, so 206- 224 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.
In Claim 205 in step a), it is unclear how exactly applicant is controlling for the claimed results of “particles…present at a concentration such that at most 1% by mass of the total amount of proteins in the biological samples are adsorbed to the particles,” and “the number of proteins identified is greater than 1000.” With respect to this, the examiner notes that no two biological samples are exactly the same. Therefore, it is unclear how applicant assures to control or use a particle concentration as claimed “such that,” “at most 1% by mass of the total amount of proteins in the biological samples are adsorbed to the particles,” and so that “the number of proteins identified is greater than 1000.”
As claimed, it would seem that only the particle concentration controls this due to the use of “such that,” but also as claimed--- the examiner it is unclear that only particle concentration would really ensure for the claimed “such that,” and “at most 1% by mass…” According to the instant specification, it seems that the “such that,” and “at most 1% by mass,” and the “number of proteins identified being greater than 1000,” is controlled by many other things in addition to the claimed “such that,” particle concentration (which can include specific particles, dilution, buffering, sample concentration, timing, concentration ratios of specific samples to specific types of particles, among other things).
Therefore, it is unclear what is meant by the “particle concentration,” “such that,” “at most 1% by mass of the total amount of proteins in the biological samples are adsorbed to the particles,” since according to the specification many other factors would/could influence the absorption onto the particles other than particle concentration, and even where disclosed in the specific the concentrations which are correlated with the claimed results are only for very specific particles types. Correction is required.
Further for Claim 206, it is claimed that the biomolecule corona comprises at most 0.01% by mass of biomolecules in the biological sample. With respect to this, the examiner notes that no two biological samples are exactly the same. Therefore, it is unclear how applicant assures in the claimed generic “biological sample,” that the biomolecule corona comprises “at most .01 % by mass of biomolecules in the biological sample.” Correction is required.
Dependent claims 207-213, 216-220 & 224 are also unclear due to their dependency on Claim 205.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 205-213, 216-220 & 224 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for certain types of particles, particle concentrations, and particles surface areas allowing for the claimed results of “particles…present at a concentration such that at most 1% by mass of the total amount of proteins in the biological samples are adsorbed to the particles,” and “the number of proteins identified is greater than 1000,” does not reasonably provide enablement for the realm of using any type of particle, or particle concentration and any other type of parameter optimizing to lead to the claimed results. The specification does not fully enable the scope of what is claimed, for any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
This decision was made in taking into consideration all of the Wands factors including:
(A) The breadth of the claims: It is noted that these claim terms, especially “particle,” and “particle concentration,” encompass a broader scope than what is shown in the specification to give the claimed results. It seems the claimed results also involve other non-claimed parameters.
(B) The nature of the invention: The nature of this invention is such that any and every particle, particle concentration and other parameters, encompassed by the claimed terms of “particle,” “particle concentration,” and the lack of other parameters claimed other than surface area/mass ratio that lead to the claimed results, is not disclosed by the instant specification.
(C) The state of the prior art: There are so many “particle,” types “particle concentration,” and other parameters which could lead to the claimed result, available in the art one would not be able to just guess or what would work to lead to the claimed results.
(D) The level of one of ordinary skill: The level of ordinary skill in this art is high, though even given that is the case, one would not be able to just work around seemingly endless parameters including pH, dilution, tailoring of aggregate substrate, buffer, time, protein corona occupancy, and electrostatics affect how and what proteins bind to the claimed particles to form the biomolecule corona and pick some to arrive at the claimed results.
(E) The level of predictability in the art: There are so many possibilities available in the art that the level of predictability of what might work and what wouldn’t is not high.
(F) The amount of direction provided by the inventor: The inventor does provide some amount of direction, in Examples 1-13, however does not provide enough direction to show how one would be able to effectively arrive at the claimed results using any particle/particle concentration/other parameters encompassed as possible by these claims.
(G) The existence of working examples: The inventor does provide working examples 1-13 but again there is not direction enough that would support effective use of any and every any particle/particle concentration/other parameter, which could be encompassed by these claims.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure: There are so many combinations of particle/particle concentration/other parameters which could be encompassed by these terms claimed, to end at the claimed results, however the quantity of experimentation would be high and consequential for someone to determine if any random particle/concentration/ other parameters led to the claimed results.
The examiner notes that from the instant specification, that applicant seems to be using some sort of equation and to adjust adsorption capacity of the particles. This is seen in the least in Figures 12, and that using various salts in conjunction with nanoparticles also allows for highly specific interactions as in Figure 17. It also seems like the nanoparticles themselves can be functionalized to allow for the specific properties claimed as in Figures 18-20. Further, Examples 1- 13 show some examples of how things such as pH, dilution, tailoring of aggregate substrate, buffer, time, protein corona occupancy, and electrostatics affect how and what proteins bind to the claimed particles to form the biomolecule corona. It does not seem that any combination of any these things gives the claimed results of “at most 1% by mass of the total amount of proteins in sample…” being absorbed to the particles, and the result of “proteins identified is greater than 1000”. For example 22A-C shows the number and types of protein groups collected/identified on carboxyl functionalized polystyrene particles (P-039) and poly(dimethylaminopropylmethacrylamide) particles (S-007 at different concentrations. Sometimes the number is 1000 as shown in Figures 22A-C and sometimes it is not. All of the things above affect the end result, therefore all of these parameters are not shown to directly connect to the claimed results of “such that,” “at most 1% by mass of the total amount of proteins in the biological samples are adsorbed to the particles,” and so that “the number of proteins identified is greater than 1000.” Applicant should limit the claims to particles and other parameters for which they have disclosure of the claimed results for, since any/all particles, particle concentrations, and other parameters, would not result in the claimed results (though it is claimed as such).
Claims 206-213, 216-220 & 224 are rejected by virtue of their dependency on Claim 205.
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.
Claim(s) 205-213, 216-220 & 224 is/are rejected under 35 U.S.C. 103 as being obvious by FAROKHZAD in US 20180172694 in view of DAWSON in US 20120046184.
With respect to Claim 205, FAROKHZAD teaches of a method of using sensor arrays for detecting/assaying biomolecules and determining a disease state in a subject (abstract).
FAROKHZAD teaches of obtaining samples from at least two subjects diagnosed with a disease or disorder and at least two control subjects; (b) contacting each sample with a sensor array to produce a plurality of biomolecule corona for each subject, and (c) comparing the composition of the plurality of biomolecule corona of the subjects with the disease or disorder to the composition of the plurality of biomolecule corona of the control subjects to determine a pattern of biomarkers associated with the disease or disorder (paragraph 0016), and further that the samples can be plasma (paragraph 0029).
FAROKHZAD teaches that the sample/plasma is contacted with a sensor array which can be a plurality of particles which bind/adsorb to the sample to form a protein corona nano-system (biomolecule corona on substrate) or corona composition (paragraphs 0012, 0023-0024, 0071, 0144, 0310-0311).
FAROKHZAD teaches that the angle of curvature on the surface of the particles/substrates can change depending on the size of the particles. This change in angle of curvature in turn change the surface area to which proteins may attach and interact with each other on the particles (paragraph 0227). As shown in FIG. 58, increasing the size of the particle results in a change in the amount of protein bound (increasing it) and also in the pattern of proteins attached to the different sized nanoparticles (in this example, the SD S-PAGE analysis of proteins on nanoparticles of diameters of 0.1 μm, 3 μm and 4 μm are shown) (paragraph 0227). From this it would have been obvious to optimize the surface area and mass of particles attached to the range claimed of 10 to 300 cm2/mg and that the number of biomolecules assayed is dependent on the substrate dimensions. "Where 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 MPEP 2144.05 and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
FAROKHZAD further teaches that the method includes analyzing for the presence of low abundance proteins, of which are only 1% of the proteome- which comprises over 10,000 proteins (paragraphs 0366-0367), and specifically of detecting low-abundance and rare proteins using multi-liposomes (paragraph 0075 & Figure 12 & paragraph 0347 & 0228). FAROKHZAD teaches that these low abundance proteins (which are detected by being adsorbed) are present at concentration of < 100 ng/ml and <10 ng/ml (paragraph 0367). This means that since the low abundance proteins are detected that the biomolecule corona comprises .1 % by mass,” of the proteins in the biofluid,” are adsorbed.
FAROKHZAD teaches of characterizing and identifying the proteins using LC-MS/MS (paragraph 0183, 0310, 0326, 0347, 0367, 0387, 0407, 0410, 0431).
FAROKHZAD and having multiple different sensor elements with the nanoparticles with varying properties or different liposomes on them (paragraph 0228, 0226). FAROKHZAD teaches of detecting low-abundance and rare proteins even in the presence of the high abundance proteins (paragraph 00254), and further that the low abundance proteins & rare proteins, are only 1% of the proteome (this also includes the .1 % by mass proteins and .01% by mass proteins) (paragraph 0366-0367).
Therefore, FAROKZHAD is in fact teaching of detecting the 1% by mass of proteins as claimed, and specifically of detecting low-abundance and rare proteins using multi-liposomes (paragraph 0075 & Figure 12 & paragraph 0347 & 0228) and a sensor array which can be a plurality of particles which bind/adsorb to the sample (paragraphs 0023-0024, 0071, 0144, 0310-0311).
However, if this is not apparent to one of ordinary skill in the art assay with respect to absorbing only low abundance protein’s (less than .1 % of proteins is a measure of abundance), DAWSON is used to remedy this.
DAWSON teaches of a method for isolation and removal of a cellular component by applying a pulse of nanoparticles (abstract, paragraph 0003), and further of harvesting and detecting very rare intracellular and low abundance cell components including rare signaling proteins (paragraph 0003, 0006). The cell component detected can be a protein that makes up less than .1% of the total protein in the serum concentration (paragraph 0012) (this also includes proteins that make up less than .01 % ), and the nanoparticles selectively bind the low abundance or rare molecule (paragraph 0013). DAWSON teaches that these rare molecules are identified from a complex biological system which includes over 1000 different biomolecules (paragraph 0021). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect lowly abundance proteins as is done in DAWSON and one would have had reasonable expectation of success to combine with FAROKHZAD due to the need in the art for better methods/systems for detection of complex protein mixtures (DAWSON, paragraph 0002).
With respect to Claim 206, FAROKHZAD teaches that the method includes analyzing for the presence of low abundance proteins, of which are only 1% of the proteome- which comprises over 10,000 proteins (paragraphs 0366-0367), and specifically of detecting low-abundance and rare proteins using multi-liposomes (paragraph 0075 & Figure 12 & paragraph 0347 & 0228). FAROKHZAD teaches that these low abundance proteins (which are detected by being adsorbed) are present at concentration of < 100 ng/ml and <10 ng/ml (paragraph 0367). This means that since the low abundance proteins are detected that “less than “about,” 1 % by mass,” of the proteins in the biofluid,” are adsorbed.
FAROKHZAD and having multiple different sensor elements with the nanoparticles with varying properties or different liposomes on them (paragraph 0228, 0226). FAROKHZAD teaches of detecting low-abundance and rare proteins even in the presence of the high abundance proteins (paragraph 00254), and further that the low abundance proteins & rare proteins, are only 1% of the proteome (this also includes the .1 % by mass proteins and .01% by mass proteins) (paragraph 0366-0367).
Therefore, FAROKZHAD is in fact teaching of detecting the 1% by mass of proteins as claimed, and specifically of detecting low-abundance and rare proteins using multi-liposomes (paragraph 0075 & Figure 12 & paragraph 0347 & 0228) and a sensor array which can be a plurality of particles which bind/adsorb to the sample (paragraphs 0023-0024, 0071, 0144, 0310-0311).
With respect to Claim 207, FAROKHZAD teaches that the angle of curvature on the surface of the particles/substrates can change depending on the size of the particles. This change in angle of curvature in turn change the surface area to which proteins may attach and interact with each other on the particles (paragraph 0227). As shown in FIG. 58, increasing the size of the particle results in a change in the amount of protein bound (increasing it) and also in the pattern of proteins attached to the different sized nanoparticles (in this example, the SD S-PAGE analysis of proteins on nanoparticles of diameters of 0.1 μm, 3 μm and 4 μm are shown) (paragraph 0227). From this it would have been obvious to optimize the surface area and mass of particles attached and that the number of biomolecules assayed is dependent on the substrate dimensions. "Where 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 MPEP 2144.05 and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). This makes the claims number of biomolecules dependent on surface size obvious- as is a result effective variable. See MPEP 2144.05.
With respect to Claim 208, FAROKHZAD teaches of incubating/contacting for 15 minutes (paragraph 0298, 0182).
With respect to Claim 209, FAROKHZAD teaches of incubating/contacting for 2 hours (paragraph 0298, 0182).
With respect to Claim 210, FAROKHZAD teaches that the detection is based on equilibrium interactions with the biomolecules (paragraph 0262). FAROKHZAD does not teach of more on the equilibrium. DAWSON is used to remedy this. DAWSON further teaches that there is constant exchange between bound proteins and free proteins that take place until and equilibrium situation is reached (paragraph 0094). Further DAWSON teaches of equilibrating until the baseline is stable (paragraph 0167). It would have been obvious to one of ordinary skill to equilibrate as is done in DAWSON in the method of FAROKHZAD due to the advantage this has in giving a stable baseline (DAWSON, paragraph 0167).
With respect to Claim 211, FAROKHZAD teaches that the sensor elements/substrates/particles can be microparticles (paragraph 0179).
With respect to Claim 212, FAROKHZAD teaches of the nanoparticles being magnetic nanoparticles (having magnetic cores) (paragraph 0215, 0382).
With respect to Claim 213, FAROKHZAD further teaches that samples can be plasma (paragraph 0029).
With respect to Claims 217-218, FAROKHZAD further teaches of identifying 1000 different sets of samples to identify the protein corona system (reads on assaying “to identify at least 1000 proteins groups”) (paragraph 0368). FAROKHZAD further teaches that the method includes analyzing for the presence of low abundance proteins, of which are only 1% of the proteome- which comprises over 10,000 proteins (paragraphs 0366-0367), and specifically of detecting low-abundance and rare proteins using multi-liposomes (paragraph 0075 & Figure 12 & paragraph 0347 & 0228).
With respect to Claim 219, FAROKHZAD teaches of the sensor element having ranges of 5 to 500 (paragraph 0164), and of the material having a wide dynamic range (paragraph 0175), and that it has a dynamic range of 10 (paragraph 0176, 0367).
The teaching of FAROKHZAD does not overlap with the claimed “at least 11”, dynamic range, however it is the Examiner’s position that the disclosed values are close enough that one of ordinary skill in the art before the effective filing date of the invention would have expected the same properties. Case law holds that a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
With respect to Claim 220, FAROKHZAD teaches that different particles/susbtrates (plural) can be used as the sensor elements and that they may be attached in different patterns (paragraph 389). This means that there can also be different concentrations of the different particles/substrates.
With respect to Claim 221, see claim 220 rejection. FAROKHZAD further teaches of the sensor element having ranges of 5 to 500 (paragraph 0164), and of the material having a wide dynamic range (paragraph 0175), and that it has a dynamic range of 10 so this makes it obvious that different particles can differ by “at least,” .25 (paragraph 0176, 0367).
With respect to Claim 222, FAROKHZAD teaches of detecting protines that have different isoforms (paragraph 0354). This is interpreted as being different than isoforms found in substrates of different surface area. It is noted that this claim is unclear as shown in the 112 rejection.
With respect to Claim 223, FAROKHZAD teaches of detecting proteins that have different isoforms (paragraph 0354). This is interpreted as being different than isoforms found in substrates of different surface area. FAROKHZHAD further teaches of analyzing modifications (paragraph 0157, 0205). It is noted that this claim is unclear as shown in the 112 rejection.
With respect to Claim 224, FAROKHZAD teaches of functionalizing with carboxylic acid (paragraph 0094, 0104, 0121-0128, 0130-0131).
Response to Arguments
Applicant's arguments filed 03/04/2026 have been fully considered but they are not persuasive.
With respect to the 101 rejection, the amendments dated 03/04/2026, makes it reasonably clear from the preponderance of evidence that the claimed identification and assaying is by performing mass spectrometry detecting using particles of relatively specific size, and that what is being claimed is not an abstract idea. Therefore, the prior 101 rejection is overcome by the amendments dated 03/04/2026.
The examiner does note that the claims would be clearer if stated that measuring or detecting by mass spectrometry is performed in the claim body. It also would be clearer if this was also reflected in the claim preamble.
With respect to the 112 rejection, the claims remain unclear, and also due to the subject matter amended 03/04/2026, the scope of enablement is also challenged. In Claim 205, applicant is essentially focusing the claims on results and has stated in arguments that the methods which leads to the claimed results which may involve many steps such as choosing concentrations of particles and sample, and other components such as dilutants, and that one of skill would know how to optimize from what is claimed, and therefore these steps do not need to be claimed. The examiner disagrees.
Even though applicant has specified in the arguments that the concentration of the particles and concentration of sample and what the sample is specifically can be selected artisan, and the skilled artisan can “readily determine the total amount of proteins in a biological sample and volume and concentration of the sample,” “then adjust “for example by dilution,” none of this is claimed. Therefore, these arguments are not commensurate in scope with the claims. As claimed, it is unclear in the claims how applicant ensures the results of “at most 1% by mass of the total amount of proteins in biological sample are absorbed,” and “the number of different proteins identified is greater than 1,000,” in any biological sample as claimed, only using the parameter of “particles,” which have a “surface area to mass ratio of from 10 to 300 cm2/mg.” As not all particle types, particle concentrations, and other parameters would result in the claimed results, since the claims can be interpreted as any particle type, any particle concentration “such that,” and any combination of other parameters used, a scope of enablement rejection is made as the instant claims have a larger scope that what is disclosed.
Further, applicant is essentially claiming just a result and stating that the “such that,” which would involve lots of choosing and optimizing, and many possible steps as shown above is clear from the claims and that one would know how to do this from what is claimed, without applicant having to make this clear in the claim language. The examiner disagrees.
The examiner notes that from the instant specification, that applicant seems to be using some sort of equation and to adjust adsorption capacity of the particles. This is seen in the least in Figures 12, and that using various salts in conjunction with nanoparticles also allows for highly specific interactions as in Figure 17. It also seems like the nanoparticles themselves can be functionalized to allow for the specific properties claimed as in Figures 18-20. Further, Examples 1- 13 show some examples of how things such as pH, dilution, tailoring of aggregate substrate, buffer, time, protein corona occupancy, and electrostatics affect how and what proteins bind to the claimed particles to form the biomolecule corona. It does not seem that any combination of any these things gives the claimed results of “at most 1% by mass of the total amount of proteins in sample…” being absorbed to the particles, and the result of “proteins identified is greater than 1000”. For example 22A-C shows the number and types of protein groups collected/identified on carboxyl functionalized polystyrene particles (P-039) and poly(dimethylaminopropylmethacrylamide) particles (S-007 at different concentrations. Sometimes the number is 1000 as shown in Figures 22A-C and sometimes it is not. Therefore, the claims are both unclear, and their complete scope is not enabled.
If applicant can overcome the 112 issues cited above, it is likely they will overcome the prior art as well.
With respect to the instant prior art, applicant argues that the cited reference do not teach of the at most 1% by mass limitation claimed in the context of protein diversity. The examiner agrees that the context in which this is taught by the references is slightly different than what claimed, however do to the 112 issues with the claims, the teachings of the prior art make the claims obvious for the time being.
Applicant further argues that the instant claims require the critical functional relationship claimed which is “using fewer particles to isolate a limited fraction of the total amount of protein in a sample results in identification of more distinct proteins than using more particles.” The examiner notes that nothing to this affect is claimed, so this argument is not commensurate in scope with the claims. What applicant seems to be doing here, is claiming that the “more distinct protein profiling,” is an unexpected result, however if this is the case, it does not seem like what is actually responsible for any unexpected result, if so, is claimed. Please fix the 112 issues above as this could help.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect lowly abundance proteins as is done in DAWSON and one would have had reasonable expectation of success to combine with FAROKHZAD due to the need in the art for better methods/systems for detection of complex protein mixtures (DAWSON, paragraph 0002).
All claims remain rejected at this time.
Conclusion
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 REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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