DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The Amendment filed on 7/15/2026 has been entered. Claims 1-20 remain pending in the application.
Claim Rejections - 35 USC § 103
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.
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) 1, 2, 6-9 and 13-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent No. 4,674,323, hereinafter Rulf in view of United States Patent No. 4,762,617, hereinafter Stevens.
Regarding claim 1, Rulf teaches an apparatus for substance separation using size-exclusion chromatography (SEC) (abstract), the apparatus comprising: a body (item 18) forming an internal 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 internal 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 internal conduit (Fig. 1A), wherein a distance between the outlet and the inlet is less than a total length of the internal 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 internal 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 (Stevens, 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).
Regarding 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).
Regarding 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).
Regarding claim 7, the limitation of 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 (Stevens, 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)).
Regarding 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 an internal 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 internal 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 internal conduit (Fig. 1A), wherein a distance between the outlet and the inlet is less than a total length of the internal conduit (Fig. 1A, the sample traverses the length of the chromatography column while the inlet and outlet are terminal connection points of the internal 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 internal 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 internal 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).
Regarding claim 9, Rulf teaches the internal conduit comprises 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).
Regarding 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 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).
Regarding claim 14, the limitation of the test 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, lines 36-37) (MPEP § 2144.05 (II)).
Regarding 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 an internal 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 internal 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 internal conduit (Fig. 1a), wherein a distance between the outlet and the inlet is less than a total length of the internal conduit (Fig. 1A, the sample traverses the length of the chromatography column while the inlet and outlet are terminal connection points of the internal 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 internal 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 internal 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).
Regarding claim 16, Rulf teaches separating the test 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).
Claim(s) 3-5, 10-12 and 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rulf and Stevens and further in view of United States Application Publication No. 2013/0134083, hereinafter Benevides.
Regarding 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).
Regarding claim 4, modified Rulf teaches a cap to enclose the coupler and protect the flexible tubing. See supra.
Regarding claim 5, modified Rulf teaches the fitting comprising a thread, a seal and a handle for installation and removal. See supra.
Regarding 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).
Regarding claim 11, modified Rulf teaches a cap to enclose the coupler and protect the flexible tubing. See supra.
Regarding claim 12, modified Rulf teaches the fitting comprising a thread, a seal, and a handle for installation and removal. See supra.
Regarding 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).
Regarding claim 18, modified Rulf teaches enclosing the coupler and the flexible tubing using a rigid cap tight-fitting onto the housing. See supra.
Regarding 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(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rulf and Stevens as applied to claim 15 above, and further in view of United States Application Publication No. 2020/0284770, hereinafter Gho.
Regarding 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 7/15/2026 have been fully considered but they are not persuasive.
Regarding applicant’s argument that Rulf nor Stevens provides any structure that may reasonably be interpreted as the claimed body forming the internal conduit and having an inlet and outlet affixed onto the body as recited in claim 1 is not found persuasive. The body is considered to be item 18, which are the five columns which are connected in series. These five columns form an internal conduit as there is a conduit which is formed from the outside of each of the columns. The fact that Rulf teaches conventional columns doesn’t prevent the ability for these conventional columns to be considered a body. The claims have not specified any additional structure with what is being considered as a body and therefore, these five columns are able to be considered as the body.
Regarding applicant’s that the office considers item 62 as the claimed inlet, however, Rulf describes item 62 as a conduit connecting the injection valve to the columns and therefore is part of the external plumbing and not affixed onto the same body the form the internal SEC conduit is not found persuasive. Item 62 is connected to the columns, as applicant has stated and therefore since item 62 is affixed to the columns, item 62 is considered to be affixed onto the body. Additionally, the sample is feed through item 62 is therefore also considered to be the inlet.
Regarding applicant’s argument that item 66 nor item 20 can be the claim outlet, this is not found persuasive. Similarly, as above, items 66 and 20 are directly or indirectly connected to the columns and therefore are considered to be “affixed” to the columns, which are considered to be the body. Additionally, the sample is feed out through items 66 and 20 and therefore either one is able to be considered to be the outlet.
Regarding applicant’s argument that item 64 cannot be considered to be the divider and using item 64 as the divider would only confirm that the rejection relies on disparate parts of an instrument rather than the claimed integrated divider structure. Firstly, the examiner points out that the claim utilizes the open transitional phrase of comprising and therefore additional structure can be present in the prior art for the prior art to read on the instant claims. Therefore, the additional structure within item 64 does not prevent the ability for item 64 to read on the claimed divider. The claim states “a divider including a body…”, and therefore as long as the prior art has a structure which is able to be considered as the divider (item 64) which includes a body (item 18), the prior art would render the claim as obvious.
Regarding applicant’s argument that the claimed distance limitation is not properly addressed by the office action is not found persuasive. The claim only states “wherein a distance between the outlet and the inlet is less than a total length of the internal conduit.” The examiner has interpreted this recitation as being the physical distance between the inlet and the outlet is less than a total length of the internal conduit. There is nothing in the current claims which would prevent this interpretation of this recitation and therefore as described above in the rejection as seen in Figure 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.
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 MATTHEW D KRCHA whose telephone number is (571)270-0386. The examiner can normally be reached M-Th 7am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at (571)270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MATTHEW D KRCHA/ Primary Examiner, Art Unit 1796
Prosecution Insights