DETAILED ACTION
In application filed on 04/13/2023, Claims 1, 3,12-13, 15,17,19, 20,32-33,42, 45-53, 60, and 62 are pending in the application. The claim set submitted on 10/27/2023 is considered because this is the most recent claim set with some preliminary amendments. Claims 1, 3, 12-13, 15, 42 and 45-53 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 02/12/2026 is acknowledged. Claims 17,19-20 and 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/12/2026.
Group I, Claims 1, 3, 12-13, 15, 42 and 45-53 are considered on the merits below.
Claim Objections
Claims 3 and 50 are objected to because of the following informalities:
Claim 3 recites “wherein at least two of the N biomarker proteins are HCC-1 and SVEP1” in line 6 of the Claim. It appears that this limitation should be recited as “or wherein at least two of the N biomarker proteins are HCC-1 and SVEP1”.
Appropriate correction is required.
Claim 50 recites “biomarker capture reagent”. However, this limitation was recited as “capture reagent” in Claim 45.
Consistent language should be use and for the purpose of expedited prosecution, Examiner interprets “biomarker capture reagent” as “capture reagent”.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 12, 15, 42, 45-46 and 48-52 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Gill et al. (US20150168423A1).
Regarding Claim 1, Gill teaches a method for detecting protein levels in a sample from a subject, comprising
forming a biomarker panel having N biomarker proteins (See Para 0052…a panel of biomarkers for evaluating the risk of a future CV event within a five year time period, wherein the panel comprises N biomarkers selected from the group consisting of the biomarkers of Table 1, wherein N=2-155), and detecting the level of each of the N biomarker proteins in a sample from the subject (See Para 0031…This method comprises the detection, in a biological sample from an individual of the population, biomarker values that each correspond to one of at least N biomarkers selected from Table 1), wherein N is at least 2 (See Para 0031… wherein N=2-155), and wherein a) at least two of the N biomarker proteins are selected from HCC-1, RNAS6, PAP 1, SVEP1, and ATL2 (this limitation is viewed as an optional limitation due to the recited “or”, thus not required by the claim ; or) b) at least one of the N biomarker proteins is selected from HCC-1, RNAS6, PAP 1, SVEP1, and ATL2 (See Table 1…HCC-1), and at least one of the N biomarker proteins is selected from N-terminal pro-BNP, RSPO4, BNP, MIC-1, FABPA, ILRL1, ANGP2, HE4, TAGL, RNAS1, and TSP2 (See Para 0028…BNP; See Para 0120…Nt-proBNP testing).
Regarding Claim 12, Gill teaches the method of claim 1, wherein all of the N biomarker proteins See Para 0052… N biomarkers selected from the group consisting of the biomarkers of Table 1, wherein N=2-155) are selected from HCC-1, RNAS6, PAP 1, SVEP1, ATL2, N-terminal pro-BNP, RSPO4, BNP, MIC-1, FABPA, ILRL1, ANGP2, HE4, TAGL, RNAS1, and TSP2 (See Table 1…HCC-1).
Regarding Claim 15, Gill teaches the method of claim 1, N is 2, N is 3, N is 4, N is 5, N is 6, N is 7, N is 8, N is 9, N is 10, N is 11, N is 12, N is 3, N is 14, N is 15, or N is 16 (See Para 0031… N=2-10).
Regarding Claim 42, Gill teaches the method of claim 1, wherein the sample is selected from a blood sample, a serum sample, a plasma sample, and a urine sample (See Para 0041…. the biological sample can be whole blood, plasma, serum, urine or the like).
Regarding Claim 45, Gill teaches the method of claim 1, wherein the method comprises contacting biomarker proteins of the sample from the subject with a set of capture reagents (See Claim 45… contacting a biological sample from the individual with at least N capture reagents), wherein each capture reagent of the set of capture reagents specifically binds (‘binding of each capture reagent to the corresponding biomarker’) to one biomarker protein being detected (See Para 0049… Such in vitro assay can include at least one capture reagent corresponding to each of the biomarkers, and can further comprise the selection of the at least one capture reagent from the group consisting of SOMAmers, antibodies, and a nucleic acid probe… binding of each capture reagent to the corresponding biomarker; See Para 0062… at least one corresponding capture reagent, wherein each of the corresponding capture reagents is specific to the selected biomarkers; and a signal generating material, said material being specific to the selected corresponding biomarkers and/or corresponding capture reagents, wherein each signal is activated up).
Regarding Claim 46, Gill teaches the method of claim 45, wherein two of the capture reagents (‘a first capture element and a second capture element’) bind to the same biomarker protein being detected (See Para 0155…
b) exposing the mixture to a first solid support including a first capture element… exposing the released SOMAmer affinity complex to a second solid support that includes a second capture element and allowing the second tag to associate with the second capture element;… i) detecting the biomarker by detecting the SOMAmer component of the SOMAmer affinity complex).
Regarding Claim 48, Gill teaches the method of claim 1, wherein the method comprises contacting biomarker proteins of the sample from the subject with a set of capture reagents (See Claim 45… contacting a biological sample from the individual with at least N capture reagents), wherein each capture reagent of the set of capture reagents specifically binds to a different biomarker protein (‘binding of each capture reagent to the corresponding biomarker’) being detected (See Para 0049… Such in vitro assay can include at least one capture reagent corresponding to each of the biomarkers, and can further comprise the selection of the at least one capture reagent from the group consisting of SOMAmers, antibodies, and a nucleic acid probe… binding of each capture reagent to the corresponding biomarker; See Para 0062… at least one corresponding capture reagent, wherein each of the corresponding capture reagents is specific to the selected biomarkers; and a signal generating material, said material being specific to the selected corresponding biomarkers and/or corresponding capture reagents, wherein each signal is activated up).
Regarding Claim 49, Gill teaches the method of claim 45, wherein each capture reagent (See Claim 45… contacting a biological sample from the individual with at least N capture reagents) is an antibody or an aptamer (See Para 0141…The aptamers are each capable of binding to a target molecule in a highly specific manner and with very high affinity).
Regarding Claim 50, Gill teaches the method of claim 49, wherein each biomarker capture reagent (See Claim 45… contacting a biological sample from the individual with at least N capture reagents) is an aptamer (See Para 0141…The aptamers are each capable of binding to a target molecule in a highly specific manner and with very high affinity).
.
Regarding Claim 51, Gill teaches the method of claim 49, wherein at least one aptamer (See Para 0141…The aptamers are each capable of binding to a target molecule in a highly specific manner and with very high affinity) is a slow off-rate aptamer (See Para 0144…As used herein, a “SOMAmer” or Slow Off-Rate Modified Aptamer refers to an aptamer having improved off-rate characteristics; See Para 0148…these slow off-rate aptamers are known as “SOMAmers.”).
Regarding Claim 52, Gill teaches the method of claim 51, wherein at least one slow off-rate aptamer (See Para 0144…As used herein, a “SOMAmer” or Slow Off-Rate Modified Aptamer refers to an aptamer having improved off-rate characteristics; See Para 0148…these slow off-rate aptamers are known as “SOMAmers”) comprises at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 nucleotides with modifications (See Para 0148…Additionally, the methods include the use of modified nucleotides in the production of candidate nucleic acid mixtures to generate aptamers or SOMAmers with improved off-rate performance, thereby teaching “at least one”).
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 3 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Gill et al. (US20150168423A1) as applied to claim 1 above, and further in view of Guild et al. (US20150366997A1).
Regarding Claim 3, Gill does not teach the method of claim 1, wherein at least two of the N biomarker proteins are RNAS6 and PAP1; or wherein at least two of the N biomarker proteins are RNAS6 and ATL2; or wherein at least two of the N biomarker proteins are HCC-1 and PAP 1; or wherein at least two of the N biomarker proteins are HCC-1 and ATL2; or wherein at least two of the N biomarker proteins are HCC-1 and RNAS6; or wherein at least two of the N biomarker proteins are PAP1 and SVEP 1; wherein at least two of the N biomarker proteins are HCC-1 and SVEP1; or wherein at least two of the N biomarker proteins are RNAS6 and SVEP1;or wherein at least two of the N biomarker proteins are PAP1 and ATL2.
In the analogous art of methods for delivery of mRNA gene therapeutic agents that lead to the production of therapeutically effective levels of proteins via a “depot effect.”, Guild teaches wherein at least two of the N biomarker proteins are RNAS6 and PAP1; or wherein at least two of the N biomarker proteins are RNAS6 and ATL2; or wherein at least two of the N biomarker proteins are HCC-1 and PAP 1; or wherein at least two of the N biomarker proteins are HCC-1 and ATL2; or wherein at least two of the N biomarker proteins are HCC-1 and RNAS6; or wherein at least two of the N biomarker proteins are PAP1 and SVEP 1; or (in light of the objection above) wherein at least two of the N biomarker proteins are HCC-1 and SVEP1; or wherein at least two of the N biomarker proteins are RNAS6 and SVEP1;or wherein at least two of the N biomarker proteins are PAP1 and ATL2.( See Table 1…SVEP1 and HCC-1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Gill to incorporate that at least… wherein at least two of the N biomarker proteins are HCC-1 and SVEP1; …as taught by Guild for the benefit of inducing expression of a polypeptide in a subject wherein the polypeptide is chosen from proteins listed in table 1 (Guild, Para 0013), allowing for the providing compositions and methods capable of ameliorating diseases associated with protein or enzyme deficiencies (Guild, Abstract).
Regarding Claim 47, Gill teaches the method of claim 46, wherein two capture reagents specifically bind to biomarker (See Para 0155…b) exposing the mixture to a first solid support including a first capture element… exposing the released SOMAmer affinity complex to a second solid support that includes a second capture element and allowing the second tag to associate with the second capture element;… i) detecting the biomarker by detecting the SOMAmer component of the SOMAmer affinity complex), and wherein the two capture reagents are aptamers (See Para 0141…The aptamers are each capable of binding to a target molecule in a highly specific manner and with very high affinity) comprising different sequences (See Para 0142…Different aptamers can have either the same or different numbers of nucleotides, thereby teaching “different sequences”).
Gill does not teach the biomarker as “SVEP1”.
In the analogous art of methods for delivery of mRNA gene therapeutic agents that lead to the production of therapeutically effective levels of proteins via a “depot effect.”, Guild teaches the biomarker proteins as SVEP1 (See Para 0118 Table 1…SVEP1).
It would have been obvious to one with ordinary skill in the art before the effective filing date to substitute the biomarker of Gill with SVEP1 of Guild because this is a substitution of equivalent elements yielding predictable results Please See MPEP 2143 (KSR Rationale B). Both references teach proteins functioning for the benefit of being used as biomarkers [Gill, Para 0168, potential protein biomarkers] and Guild [Para 0117…secreted proteins…SVEP1), allowing for the providing compositions and methods capable of ameliorating diseases associated with protein or enzyme deficiencies (Guild, Abstract).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Gill et al. (US20150168423A1) as applied to claim 1 above, and further in view of Campton et al. (US20190317080A1).
Regarding Claim 13, Gill does not teach that the method of claim 1, wherein one of the N biomarker proteins is MIC-1 or one of the N biomarker proteins is RNAS1.
In the analogous art of disclosure relating generally to detection and, in particular, to labeling biomarkers on target analytes, Campton teaches that wherein one of the N biomarker proteins is MIC-1 or one of the N biomarker proteins is RNAS1 (See Para 0014… The biomarker or biomarkers include, but are not limited to: MIC-1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Gill to incorporate that the N biomarker proteins is MIC-1 or one of the N biomarker proteins is RNAS1 as taught by Campton for the benefit of using MIC-1 as a target molecule for drug delivery (Campton, Para 0013), allowing for the provisions of kits, compositions, and methods for labeling target materials or target analytes (Campton, Abstract).
Claim 53 is rejected under 35 U.S.C. 103 as being unpatentable over Gill et al. (US20150168423A1) as applied to claim 51 above, and further in view of Zichi et al. (US20090004667A1).
Regarding Claim 53, Gill teaches the method of claim 51, wherein each slow off-rate aptamer (See Para 0144…As used herein, a “SOMAmer” or Slow Off-Rate Modified Aptamer refers to an aptamer having improved off-rate characteristics; See Para 0148…these slow off-rate aptamers are known as “SOMAmers”) binds to its target protein (See Para 0145…the selection of aptamers that interact with a target molecule in a desirable manner, for example binding with high affinity to a protein,…The SELEX process can be used to identify aptamers with high affinity to a specific target or biomarker) with an off rate (t(1/2)) (See Para 0148…off-rate).
Gill does not teach wherein each slow off-rate aptamer binds to its target protein with an off rate (t(1/2)) of > 30 minutes, > 60 minutes, > 90 minutes,> 120 minutes,> 150 minutes,> 180 minutes,> 210 minutes, or > 240 minutes.
In the analogous art of improved SELEX methods for producing aptamers that are capable of binding to target molecules and improved photoSELEX methods for producing photoreactive aptamers that are capable of both binding and covalently crosslinking to target molecules, Zichi teaches wherein each slow off-rate aptamer binds to its target protein (See Para 0002… slow off-rate aptamers that are highly specific to a target of interest.) with an off rate (t(1/2)) of > 30 minutes, > 60 minutes, > 90 minutes,> 120 minutes,> 150 minutes,> 180 minutes,> 210 minutes, or > 240 minutes (See Para 0044….As used herein, “slow off-rate” or “slow rate of dissociation” or “slow dissociation rate” refers to the time it takes for an aptamers/target complex to begin to dissociate. This can be expressed as a half life, t1/2, or the point at which 50% of the aptamer/target complex has dissociated. The off-rate or dissociation rate of a slow off-rate aptamer, expressed as t1/2 values, can be about ≧30 min., ≧60 min., ≧90 min., ≧120 min.≧150 min.≧180 min.≧210 and about ≧240 min).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Gill to incorporate that each slow off-rate aptamer binds to its target protein with an off rate (t(1/2)) of > 30 minutes, > 60 minutes, > 90 minutes,> 120 minutes,> 150 minutes,> 180 minutes,> 210 minutes, or > 240 minutes, as taught by Zichi for the benefit of providing the time it takes for an aptamers/target complex to begin to dissociate (Zichi, Para 0044), allowing for provision of novel processes and techniques that favor the selection of slow off-rate aptamers while inhibiting the selection of aptamers that simply have a fast association rate with the target. Also for the provision of aptamer constructs that include different built-in functionalities. These functionalities may include tags for immobilization, labels for detection, means to promote or control separation, etc (Zichi, Para 0009).
Conclusion
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797