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 .
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 (i.e., changing from AIA to pre-AIA ) 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/10/2026 has been entered.
Status of Claims
Claims 13-15 and 17-27 are pending and under examination. Claims 1-12 and 16 are canceled.
Information Disclosure Statement
The information disclosure statement (IDS) documents submitted on 04/03/2025 and 07/23/2025 have been considered by the examiner.
Maintained Rejection
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.
Claims 13-15 and 17-27 are rejected under 35 U.S.C. 103 as being unpatentable over Koninklijke Philips Electronics (EP2541250A1, published 01/02/2013, IDS submitted on 6/13/2022, cite # 3 under Foreign Patent Docs.) in view of Nishio et al. (US2013/0267040A1, published 10/10/2013, of record dated 08/03/2023) and He et al. (US20130065780A1, published 03/14/2013, of record dated 08/03/2023), as evidenced by Thermo Fisher (Polyethylene Glycol (PEG) and PEGlyation of Proteins, print retrieved on 10/21/2019, of record dated 08/03/2023).
Koninklijke Philips Electronics (KPE) teaches an assay for the detection of specific target biomolecules from a sample and/or determination of the concentration of specific target biomolecule (see abstract). KPE teaches coating spacer molecules that enable effective capture of target molecules (see para. [0008]). KPE further teaches a molecular architecture on magnetic particles for affinity assays with low non-specific binding wherein a protein with multiple binding sites such as streptavidin, having a high affinity for biotin with a spacer molecule preferably comprises polyethylene glycol (see abstract). Figure 1 depicts an analyte in a microparticle-based analyte-specific binding assay wherein said microparticles are coated with streptavidins (first binding pair) and biotinylated antibody (see right col., para. [0152]; i.e., analyte-specific binding agent bound to the second partner). KPE teaches the size of a particle envisaged by the present invention may vary and preferred particles are in the nanometer and micrometer range and up to several micrometers (see para. [0113]). KPE also teaches masterbeads 500 nm, streptavidin coated (see right col., para. [0152]). Additionally, KPE teaches the affinity molecule may be peptides (see paras. [0011] and [0068]).
KPE teaches that streptavidin-coated particle is used as starting material (see para. [0039] under Fig. 1). KPE teaches the non-affine spacers are polymeric molecules that have a certain length and strength in order to be able to act like polymeric fibers (see para. [0076]). KPE teaches suitable non-affine spacer molecules is polyethylene glycol and one of the preferred lengths is 10 nm (see paras. [0077] and [0089]). KPE further teaches polyethylene glycol non-affine spacer molecules may be any polyethylene which are not provoking a specific molecular binding reaction in particular no molecular binding reaction interfering with an affinity molecule and such polyethylene glycols maybe of different compositions and/or lengths (see para. [0089]). KPE teaches the particles comprising streptavidin and biotin-coupled PEG spacer of a length of about 40 nm together with an anti-PSA antibody (see para. [0095]). Figure 1 shows biotinylated antibody is bound to streptavidin:
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The evidentiary teachings of Thermo Fisher indicate that length of (PEG)24 is about 95.2 angstrom (Å) (see pg. 4), which is ~ 9.52 nm.
Even though KPE teaches polyethylene glycol spacers are up to 10nm in length (see para. [0077]), the reference does not explicitly teach a linker comprising from 12 to 24 ethylene glycol units; and in separate containers or in separated compartments of a single container.
Nishio teaches a novel peptide capable for binding to rhodium nanoparticle (see abstract and para. [0011]). Nishio further teaches in Figs. 2-3 that avidin (104) and biotin-PEG12-peptide (105). Nishio further teaches that in experiment 1, the following solutions were prepared: biotin-PEG12-peptide solution, avidin aqueous solution, ((see paras. [0023]-[0027]). Nishio teaches NHS-PEG12-Biotin has a spacer arm of 56 angstrom (Å) (see para. [0043]).
He teaches fluorescent conjugated polymers in conjunction with barcoded nanoparticles (see abstract and para. [0002]). He teaches a kit comprising individual premeasured containers of reagents were used (see paras. [0019] and [0021]). He also teaches that streptavidin-biotin linkage (see paras. [0018] and [0081]). He teaches protein target is prostate specific antigen (PSA) (see para. [0022]).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used polyethylene glycol (PEG) non-affine spacers that are up to 10 nm in length of Koninklijke Philips Electronics (KPE) because KPE teaches PEG spacers that are up to 10 nm are suitable lengths to conjugate between affinity molecules (binding pair) and analyte-specific binding agent and PEG spacers are modifiable at different compositions (e.g., branches) and lengths for attaching to different affinity molecules and PEG spacers do not provoke non-specific binding reaction. As stated above, the evidentiary teachings of Thermo Fisher indicate that (PEG)24 is about ~ 9.52 nm (e.g., PEG24 has 24 ethylene glycol units). Because KPE teaches that polyethylene glycol non-affine spacers overlap with the claimed range of 12 to 24 ethylene glycol units, it would be prima facie obvious to have used a linker comprising 12-24 ethylene glycol units in KPE’s microparticles.
Furthermore, it would have been obvious to the person to have used the biotinylated affinity molecules of KPE with the PEG12 spacer of Nishio because KPE teaches that the PEG spacers conjugating between biotin and affinity molecules are modifiable in length and up to 10 nm are suitable lengths, as it would adapt particular affinity molecules conjugating to microparticles and Nishio teaches that biotin-PEG12 spacer is effective to couple peptides onto nanoparticles. Thus, the person would have used an effective PEG spacer to conjugate peptides onto KPE’s microparticles because KPE recognizes using peptides as affinity molecules on the microparticles.
Additionally, advantages of packaging essential reagents in a kit form have been well recognized in the art at the time of invention. For example, He teaches a kit comprising individual premeasured containers of reagents were used (see paras. [0019] and [0021]). Therefore, it would have been obvious to the person to have packaged and stored the biotinylated agent separately from microparticles coated with streptavidins of KPE because kits with separately packaged reagents can be premeasured for specific reactions/assays, as taught by He; and for the purpose of commercial sales, said reagents would stably be stored without premature reactivities.
The person would have reasonably expected success in using PEG12 spacer while storing the reagents separately in containers because it has been well understood in the art that biotin is reactive to streptavidin in the presence of PEG and these reagents are separately stable prior to assay reactions.
Note that even though He teaches a kit, the terminology “kit” is not found to further limit the scope of the claims beyond requiring the reagents to be separated in containers or compartments, as these are the sole constituent reagents of the kit. The terminology of a “kit” does not clearly invoke any additional ingredients or provide antecedent basis for terms appearing in the body of the claim. See also MPEP 2111.02.
With regard to claim 14, KPE teaches a molecular architecture on magnetic particles for affinity assays with low non-specific binding wherein a protein with multiple binding sites such as streptavidin, having a high affinity for biotin with a spacer molecule preferably comprises polyethylene glycol (see abstract, para. [0095], and Fig. 1).
With regard to claim 15, KPE further teaches detection molecule is a label wherein the label is fluorescent dyes (see para. [0130] and Fig. 6, step 5 detection). KPE teaches detection molecules are antibodies (see right col., para. [0128]). KPE does not explicitly teach in a separate container. However, it would have been obvious to the person to have separated the labeled antibody reagent of KPE in an individual container because reagents are held in individual containers prior to assaying. Therefore, the person would have separately stored labeled antibodies from the other reagents because antibody interactions will occur even in the absence of target analyte.
With regard to claim 17, KPE teaches superparamagnetic nanoparticles (see para. [0118]).
With regard to claim 18, KPE teaches molecule vary about 35 amino acids to about 500 amino acids (see right col., para. [0086]). Because the claimed range overlaps with the range disclosed by the prior art, a prima facie case of obviousness exists.
With regard to claim 19, KPE teaches molecule may vary about 35 amino acids to about 500 amino acids (see para. [0072] and right col., para. [0086]).
With regard to claim 20, Figure 1 depicts an analyte in a microparticle-based analyte-specific binding assay with biotinylated antibody (see right col., para. [0152]). Additionally, KPE teaches the affinity molecule may be peptides (see paras. [0011] and [0068]).
With regard to claim 21, the recitation of “instructions for measuring an analyte” is not found to be limiting in such a case as this; where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004). See MPEP 2112.01.
With regard to claim 22, Fig. 1 of KPE shows the two biotins bound to one antibody (left figure) and at five biotins to one antibody (right figure). Thus, the amount of biotin to antibody is higher.
With regard to claims 23-26, Fig. 1 of KPE shows the two biotins bound to one antibody (left figure) and at five biotins to one antibody (right figure). Additionally, He teaches a kit comprising individual premeasured containers of reagents were used (see paras. [0019] and [0021]). The references do not explicitly teach the claimed molar ratio ranges. However, it has been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum range of molar ratio with biotins for a specific result-effective variable in conjugating to streptavidins. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation" Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” As stated above, KPE teaches using a higher amount of biotin to antibody because multiple biotins on an antibody bind to multiple streptavidins. Thus, it would have been obvious to the person of ordinary skill to discover the optimum molar ratios as claimed for a specific assay detection.
With regard to claim 27, KPE has been discussed above, the reference does not explicitly teach “ a kit consisting essentially of” and a linker comprising from 12 to 30 ethylene glycol units; and in separate containers or in separated compartments of a single container. Also, Nishio, He and Thermo Fisher have been discussed above.
However, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used polyethylene glycol (PEG) non-affine spacers that are up to 10 nm in length of Koninklijke Philips Electronics (KPE) because KPE teaches PEG spacers that are up to 10 nm are a suitable lengths as spacers to conjugate affinity molecules and PEG spacers are modifiable at different compositions and lengths for attaching to different affinity molecules and PEG spacers do not provoke non-specific binding reaction. As stated above, the evidentiary teachings of Thermo Fisher indicate that (PEG)24 is about ~ 9.52 nm. Therefore, it would have been obvious that polyethylene glycol non-affine spacers that are up to 10 nm in length would overlap with the claimed range of 12 to 30 ethylene glycol units (e.g., PEG24 has 24 ethylene glycol units).
Furthermore, it would have been obvious to the person to have used the biotinylated affinity molecules of KPE with the PEG12 spacer of Nishio because KPE teaches that the PEG spacers conjugating between biotin and affinity molecules are modifiable in length and up to 10 nm are suitable lengths, as it would adapt particular affinity molecules conjugating to microparticles and Nishio teaches that biotin-PEG12 spacer is effective to couple peptides onto nanoparticles. Thus, the person would have used an effective PEG spacer to conjugate peptides onto KPE’s microparticles because KPE recognizes using peptides as affinity molecules on the microparticles.
Additionally, advantages of packaging essential reagents in kit form were well known in the art at the time of invention. For example, He teaches a kit of individual premeasured containers of reagents were used (see paras. [0019] and [0021]). Therefore, it would have been obvious to the person to have packaged and stored the biotinylated agent separately from microparticles coated with streptavidin of KPE and separately stored consisting essentially of said reagents because (1) KPE shows in Fig. 1 that the reaction is only consisted essentially of said reagents and (2) separately packaged reagents can be premeasured for specific reactions/assays, as taught by He; and for the purpose of commercial sales, said reagents would stably be stored without premature reactivities.
The person would have reasonably expected success in using PEG12 spacer while storing the reagents separately in containers because it has been well understood in the art that biotin is reactive to streptavidin in the presence of PEG and these reagents are separately stable prior to assay reactions.
Note that even though He teaches a kit, the terminology “kit” is not found to further limit the scope of the claims beyond requiring the reagents to be separated in containers or compartments, as these are the sole constituent reagents of the kit. The terminology of a “kit” does not clearly invoke any additional ingredients or provide antecedent basis for terms appearing in the body of the claim. See also MPEP 2111.02.
Response to Arguments
Applicant's arguments filed 03/10/2026 have been fully considered but they are not persuasive with respect to the 35 U.S.C. 103 rejection of record.
Applicant argues on page 7 that the claimed range of 12 to 24 ethylene glycol units produces unexpected results contrary to prior art teaching. Applicant argues that instant specification cited Patent No. 5521319 [0080] states that linker length should be short i.e., up to 5 units of ethylene oxide. Applicant argues on page 8 that Table 3 in the instant specification shows the unexpected results of PEG12 to PEG24. Applicant argues on page 9 that the performance improvement is non-linear because performance peaks within the claimed 12-24 range and then declines. The specification also confirms that linkers comprising between 12 and 30 ethylene glycol units are quite superior over the shorter as well as the longer linker. Applicant argues on page 10 that the prior art did not recognize PEG linker length in the 12-24 unit range as a result-effective variable for diagnostic immunoassay performance. Applicant argues on pages 11-12 that KPE preferred is PEG 10,000 which is 10 times the upper limit of the claimed 12-24 range. In Example 2 of KPE, the spacers have a range of higher than 3.5 kDa, which corresponds to a length of approximately 40 nm. Thus, KPE’s PEG spacers serve as non-affine spacer molecules forming a mesh—a steric barrier to prevent non-specific binding by creating a 3D network around the affinity molecules, which is different from the instant claims. Applicant also argues on pages 13-14 that Nisho is different from KPE and He does not cure the deficiencies. Applicant argues pages 14-15, that claims 22-27 are patentable for the reasons set forth in arguments above.
The arguments are not found persuasive for the following reasons. Note that the claims are directed to a product (kit) and not a process. Therefore, structures are essential to the claimed invention. Meanwhile, claims 13 and 27 are directed to the limitations of a linker comprising from either 12- 24 or 12-30 ethylene glycol units are open-ended recitations. These limitations are not the same as instant Table 3 where discrete PEG spacers are used with the analyte-specific binding agent. For example, a linker comprising from 12 to 24 units may contain other chemical structures and/or a plurality of 12-24 PEG branches. As evidenced by KPE, PEGs are not only linear but also circular, branched-like molecules (see para. [0078]). Therefore, the claimed spacers are not limited to discrete PEG12 to PEG24, which are linear (Table 3). Meanwhile, as stated in the rejection statement, it would have been obvious to the person to have used polyethylene glycol (PEG) non-affine spacers that are up to 10 nm in length of KPE because KPE teaches PEG spacers that are up to 10 nm are suitable lengths as spacers and PEG spacers do not provoke non-specific binding reaction. Meanwhile, Thermo Fisher indicates that (PEG)24 is about ~ 9.52 nm. Because KPE teaches that polyethylene glycol non-affine spacers overlap with the claimed range of 12 to 24 ethylene glycol units, it would be prima facie obvious. KPE does teach that the PEG spacers serve as non-affine spacer molecules forming a mesh and the PEG spacers are bound to antibody (analyte-specific binding agent) and biotin (see Fig. 1). Structurally, the claimed linker comprising from 12-24 ethylene glycol units could produce a mesh coating.
With respect to arguments of KPE’s examples using PEG with much higher limits than 12-24 range, the arguments are not found persuasive because the claimed linker is not consisted of just 12-24 or 12-30 ethylene glycol units. As stated above, the recited linker may contain a plurality of branches of 12-24 or 12-30 ethylene glycol units.
With respect to Nishio, the arguments are not found persuasive. Both KPE and Nishio teach using biotin with PEG for conjugation. Therefore, it would have been obvious to the person to have used the biotinylated affinity molecules of KPE with the PEG12 spacer of Nishio because KPE teaches that the PEG spacers conjugating between biotin and affinity molecules are modifiable in length and Nishio teaches that biotin-PEG12 spacer is effective to couple peptides onto nanoparticles. It is noted that the claimed microparticles also encompass nanoparticle sizes (see pg. 5, lines 15-24, of filed specification dated 06/13/2022).
With respect to Patent No. 5521319, even though the patent teaches short PEGs are used and useful, KPE recognizes a wide range of PEG sizes are used. However, the rejection is not based on the Patent No. 5521319 but rather KPE, Nishio, and He, as evidenced by Thermo Fisher.
With respect to superior and unexpected results provided by Table 3, the arguments are not found persuasive because Applicant has not provided evidence that commensurate in scope with the claimed subject matter. To show unexpected results, the evidence must be (1) commensurate in scope with the claimed subject matter, In re Clemens, 622 F.2d 1019, 1035, 206 USPQ 289, 296 (CCPA 1980), (2) show what was expected, to "properly evaluate whether a … property was unexpected", and (3) compare to the closest prior art. Pfizer v. Apotex, 480 F.3d 1348, 1370-71, 82 USPQ2d 1321, 1338 (Fed. Cir. 2007).
In this particular case, Table 3 contains specific limitations to chemical structures of PEG12 – PEG24 with specific binding pair (biotin-streptavidin), microparticles (specific sizes), antibody, and molar ratios to produce the superior or unexpected results as disclosed in the instant Table 3. Although KPE is the closest prior art of record, the claims are not commensurate in scope with the results from the disclosure.
With respect to claims 22-26, the arguments are not found persuasive for all the reasons stated above.
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678