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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 23, 2026 has been entered.
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 1-2, 6-9, 13-16, are rejected under 35 U.S.C. 103 as being unpatentable over Rulf et al. (“Rulf”)(US 4,674,323) in view of Stevens (US 4,762,617).
With respect to claim 1, Rulf teaches an apparatus for substance separation using size-exclusion chromatography (SEC) (abstract), the apparatus comprising: a body (item 18) forming a conduit for enclosing a resin composite for the substance separation using SEC (Fig. 1A, the chromatography column defines a fluid flow passage through chromatographic media); an inlet (item 62) affixed onto the body and fluidly connected to the conduit (Fig. 1A), the conduit inlet configured to receive a test sample for SEC separation (abstract); and an outlet (item 66) affixed onto the body and coupled to the conduit (Fig. 1A), wherein a distance between the outlet and the inlet is less than a total length of the conduit (Fig. 1A, the sample traverses the length of the chromatography column while the inlet and outlet are terminal connection points of the conduit such that the total conduit length exceeds the physical distance between the inlet and outlet).
Rulf does not teach the resin composite in the conduit.
Stevens teaches a size-exclusion chromatography system which utilizes a resin composite which is cross-linked agarose as it minimizes interaction between the solvent and the matrix (column 4, lines 4-8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have filled the conduit with cross-linked agarose as the resin composite because it would minimize interactions between the solvent and the matrix (Stevens, column, lines 28-29).
With respect to claim 2, Rulf teaches a conduit comprising a plurality of parallel tubes (item 18), each having a coupler at each end (Fig. 1A) for connecting two or more of the plurality of parallel tubes in a series (column 3, lines 28-29).
With respect to claim 6, Rulf teaches a conduit where the sample is pumped through, and an absorbance value is measurable (column 5, lines 26-29).
Modified Rulf teaches the conduit is filled with a resin composite comprising a cross-linked agarose. See supra.
Regarding the test sample comprising plasma that when the plasma is pumped through the conduit an absorbance value of a lipoprotein in the plasma is measurable are limitations direct to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by Rulf and Stevens and the apparatus of modified Rulf is capable of performing the claimed functions. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Rulf (see MPEP §2114).
With respect to claim 7, regarding the test sample volume, these limitations are directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by Rulf and Stevens and the apparatus of modified Rulf is capable of having a sample volume ranged between 50 and 200 micro liters. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Rulf (see MPEP §2114).
Rulf and Stevens do not teach that the cross-linked agarose has a particle size between 9 and 30 microns. Stevens teaches that the filtration time is dependent on the size of particles (column 1, lines 36-37).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to determine, through routine experimentation, that optimum particle size in the range of 8 and 30 microns would allow the desired filtration time to be achieved based on the size of the particles (Stevens, column 1, lines 36-37)(MPEP § 2144.05 (II)).
With respect to claim 8, Rulf teaches a system for substance separation using size-exclusion (SEC)(abstract), the system comprising: a liquid chromatography pump (item 14); a liquid chromatography ultra-violet (UV) detector (item 22; column 5, lines 17-22); and a divider (item 64) including: a body (item 18) forming a conduit for enclosing a resin composite for the substance separation using SEC (Fig. 1A, the chromatography column defines a fluid flow passage through chromatographic media), an inlet (item 62) affixed onto the body and fluidly connected to the conduit (Fig. 1A), the inlet configured to receive a test sample pumped from the liquid chromatography pump (column 5, lines 55-65) for SEC separation; and an outlet (item 20) affixed onto the body (item 18) and coupled to the conduit (Fig. 1A), wherein a distance between the outlet and the inlet is less than a total length of the conduit (Fig. 1A, the sample traverses the length of the chromatography column while the inlet and outlet are terminal connection points of the conduit such that the total conduit length exceeds the physical distance between the inlet and outlet), and wherein the outlet provides substances separated from the test samples by the divider to the liquid chromatography UV detector (item 22, column 5, lines 17-22).
Rulf does not teach the resin composite in the conduit.
Stevens teaches a size-exclusion chromatography system which utilizes a resin composite which is cross-linked agarose as it minimizes interaction between the solvent and the matrix (column 4, lines 4-8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have filled the conduit with cross-linked agarose as the resin composite because it would minimize interactions between the solvent and the matrix (Stevens, column, lines 28-29).
With respect to claim 9, Rulf teaches a conduit comprising a plurality of parallel tubes (item 18), each having a coupler at each end (Fig. 1A) for connecting two or more of the plurality of parallel tubes in a series (column 3, lines 28-29).
With respect to claim 13, Rulf teaches a conduit where the sample is pumped through, and an absorbance value is measured by the liquid chromatography UV detector (column 5, lines 17-22 and 26-29).
Modified Rulf teaches the conduit is filled with a resin composite comprising a cross-linked agarose. See supra.
Regarding the test sample comprising plasma that when the plasma is pumped through the conduit an absorbance value of a lipoprotein in the plasma is measurable are limitations direct to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by Rulf and Stevens and the apparatus of modified Rulf is capable of performing the claimed functions. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Rulf (see MPEP § 2114).
With respect to claim 14, regarding the rest sample volume, these limitations are directed to the function of the apparatus and/or the manner or operating the apparatus, all the structural limitations of the claim has been disclosed by Rulf and Stevens and the apparatus of modified Rulf is capable of having a sample volume ranged between 50 and 200 micro liters. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Rulf (see MPEP § 2114).
Rulf and Stevens do not teach that the cross-linked agarose has a particle size between 9 and 30 microns. Stevens teaches that the filtration time is dependent on the size of particles (column 1, lines 36-37).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to determine, through routine experimentation, that optimum particle size in the range of 8 and 30 microns would allow the desired filtration time to be achieved based on the size of the particles (Stevens, column 1, line s36-37)(MPEP § 2144.05 (II)).
With respect to claim 15, Rulf teaches a method for substance separation using size-exclusion chromatography (SEC), the method comprising: providing a test sample using a liquid chromatography pump (Fig, 8B) to an inlet of a divider (Fig. 1A); separating a substance from the test sample in a conduit contained in a body of the divider (column 18, lines 9-18), a body (item 18) forming a conduit for enclosing a resin composite for the substance separation using SEC (Fig. 1A, the chromatography column defines a fluid flow passage through chromatographic media), wherein the inlet (item 62) is affixed onto the body and fluidly connected to the conduit (Fig. 1A) for receiving the test sample for SEC separation (abstract);
and providing the substance separated from the test samples by the resin composite to a liquid chromatography ultra-violet (UV) detector via an outlet of the divider (item 22, column 5, lines 17-22), the outlet (item 20) affixed onto the body (item 18) and coupled to the conduit (Fig. 1a), wherein a distance between the outlet and the inlet is less than a total length of the conduit (Fig. 1A, the sample traverses the length of the chromatography column while the inlet and outlet are terminal connection points of the conduit such that the total conduit length exceeds the physical distance between the inlet and outlet).
Rulf does not teach the resin composite in the conduit.
Stevens teaches a size-exclusion chromatography system which utilizes a resin composite which is cross-linked agarose as it minimizes interaction between the solvent and the matrix (column 4, lines 4-8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have filled the conduit with cross-linked agarose as the resin composite because it would minimize interactions between the solvent and the matrix (Stevens, column, lines 28-29).
With respect to claim 16, Rulf teaches the method of claim 15, wherein separating the rest sample in the conduit contained in the housing comprises: separating the test sample in a plurality of parallel tubes (column 18, lines 16-18), each of the plurality parallel tubes having a coupler at each end (Fig. 1A) for connecting two or more of the plurality or parallel tubes in series (column 3, lines 28-29).
Claims 3-5, 10-12, 17-19, are rejected under 35 U.S.C. 103 as being unpatentable over Rulf et al. (“Rulf”)(US 4,674,323) in view of Stevens (US 4,762,617) in further view of Benevides et al. (“Benevides”)(US 2013/0134083 A1).
With respect to claim 3, Rulf teaches coupling (Fig. 1A) the plurality of parallel tubes (item 18).
Rulf and Stevens do not teach that the coupler comprises a fitting and a flexible tubing.
Benevides teaches a coupler/connector (Figure 5) comprising a fitting 510, flexible tubing 500a, a cap/ferrule 520, a thread, a seal, and a handle/fitting nut 530 where the fitting sealingly connects an open end of the tubing so that it provides a seal against leaks (paragraphs 0088-0089).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized a fitting which has a thread, a seal, handle, a cap and flexible tubing as the coupler because Benevides teaches that the fittings provide a seal against leaks (paragraph 0088).
With respect to claim 4, modified Rulf teaches a cap to enclose the coupler and protect the flexible tubing. See supra.
With respect to claim 5, modified Rulf teaches the fitting comprising a thread, a seal and a handle for installation and removal. See supra.
With respect to claim 10, Rulf teaches coupling (Fig. 1A) the plurality of parallel tubes (item 18).
Rulf and Stevens do not teach that the coupler comprises a fitting and a flexible tubing.
Benevides further teaches a coupler/connecter (figure 5) comprising a fitting 510, flexible tubing 500a, a cap/ferrule 520, a thread, a seal, and a handle/fitting nut 530 where the fitting sealingly connects an open end of the tubing so that it provides a seal against leaks (paragraphs 0088-0089).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized a fitting which has a thread, a seal, a handle, a cap and flexible tubing as the coupler because Benevides teaches that the fittings provide a seal against leaks (paragraph 0088).
With respect to claim 11, modified Rulf teaches a cap to enclose the coupler and protect the flexible tubing. See supra.
With respect to claim 12, modified Rulf teaches the fitting comprising a thread, a seal, and a handle for installation and removal. See supra.
With respect to claim 17, Rulf teaches coupling (Fig. 1A) the plurality of parallel tubes (item 18).
Rulf and Stevens do not teach sealingly connecting an open end of the flexible tubing to a corresponding one of the plurality or parallel tubes using a fitting of the coupler.
Benevides further teaches a coupler/connector (figure 5) comprising a fitting 510, flexible tubing 500a, a cap/ferrule 520, a thread, a seal, and a handle/fitting nut 530 where the fitting sealingly connects an open end of the tubing so that it provides a seal against leaks (paragraphs 0088-0089).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized a fitting which has a thread, a seal, handle, a cap and flexible tubing as the coupler because Benevides teaches that the fittings provide a seal against leaks (paragraph 0088).
With respect to claim 18, modified Rulf teaches enclosing the coupler and the flexible tubing using a rigid cap tight-fitting onto the housing. See supra.
With respect to claim 19, modified Rulf teaches rotating the fitting of the coupler onto the plurality of parallel tubes via an intermediate connector providing female threads for receiving male threads on the fitting of the coupler and male threads on the plurality of parallel tubes. See supra.
Claim 20, is rejected under 35 U.S.C. 103 as being unpatentable over Rulf et al. (“Rulf”)(US 4,674,323) in view of Stevens (US 4,762,617) in further view of Gho et al. (“Gho”)(US 2020/0284770 A1).
With respect to claim 20, modified Rulf teaches filing the conduit with resin composite having a cross-linked agarose (see supra) and pumping the test sample through the conduit (column 5, lines 55-65) for measuring an absorbance value using the liquid chromatography UV detector (column 5, lines 17-22 and 26-29).
Rulf and Stevens do not teach the test sample is plasma.
Gho teaches a method using size exclusion chromatography on blood plasma which looks for extracellular vesicles (paragraph 0029) so that the extracellular vesicles can be separated to monitor cancer progression metastasis or angiogenesis (paragraph 0003).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to analyze blood plasma using the apparatus of modified Rulf because the extracellular vesicles can be separated to monitor cancer progression metastasis or angiogenesis (Gho, paragraph 0003).
Response to Arguments
Applicant's arguments filed April 16, 2026 have been fully considered but they are not persuasive.
Applicant argues that the rejection should be withdrawn because Rulf nor Stevens do not disclose a body forming a conduit for enclosing a resin composite for the substance separation using SEC, an inlet affixed onto the body and an outlet affixed onto the body. Remarks 6-7. The basis of the argument is that Rulf does not disclose or suggest at least a body forming a conduit for enclosing a resin composite for the substance separation using SEC as recited in the amended claim 1.
Applicant made amendments to independent claims 1, 8 and 15. Amendments to these
claims added the limitation of “a body forming a conduit for enclosing a resin composite for the substance separating using SEC” and “the body and fluidly connected to the conduit, the inlet configured to receive”.
Examiner is interpreting the recited “body” to mean a chromatography column body or housing that defines a fluid flow passage through chromatographic media.
Fig. 1A of Rulf shows inlet 62 and outlet 66 operatively connected to the chromatographic column through which the sample enters and exits the chromatographic flow path. Accordingly, inlet 62 and outlet 66 are attached to and associated with the column body defining the conduit.
The argument is not persuasive because Rulf in view of Stevens still teaches the added limitation in Rulf, Fig. 1 and Stevens, column 4, lines 4-8 (teaches the resin composite), rendering the rejection applicable notwithstanding applicant’s prior position.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brianna K. Slade whose telephone number is (571)272-8514. The examiner can normally be reached Monday - Friday 8:30 AM - 2:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan V. Van can be reached at (571) 272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.K.S./Examiner, Art Unit 1796
/MATTHEW D KRCHA/Primary Examiner, Art Unit 1796
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