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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/13/2026 has been entered.
Status of the Claims
Claims 1-17 and 19-21 are pending.
Claims 1, 4-5, 9, 16 and 19-20 are newly amended.
Claim 21 is newly added.
Claims 1-17 and 19-21 are under examination on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 1, 4, 8-9, 13, 16-20 under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) is withdrawn in order to address the claimed as amended.
The rejection of claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) and Bangs Laboratory (ProMag HP Magnetic Microspheres, retrieved from internet 07/22/2025) is withdrawn in order to address the claimed as amended.
The rejection of claims 2-3 and 6-7 under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025), as applied to claim 1 above, and further in view of Banfi et al. (Clin Chem Lab Med, 2007) and Dickinson (Krackeller Scientific, retrieved from Internet Archive, archived June 24, 2022) is withdrawn in order to address the claimed as amended.
The rejection of claims 5 and 10 under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025), as applied to claims 1 and 4 above, and further in view of Golias et al. (US4811866A, 1989) is withdrawn in order to address the claimed as amended.
The rejection of claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025), as applied to claim 1 above, and further in view of Pectu et al. (Applied Surface Science, 2015) is withdrawn in order to address the claimed as amended.
The rejection of claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025), as applied to claim 1 above, and further in view Zeng et al. (Thrombosis Research, 2020) is withdrawn in order to address the claimed as amended.
The rejection of claims 15 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025), as applied to claim 1 above, and further in view of Murto et al. (US6689615B1, on IDS 06/12/2025) is withdrawn in order to address the claimed as amended.
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.
Claims 1, 4, 8-9, 12-13, 16-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020, previously cited) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025, previously cited) and MTC Bio (ordering information, 2018, previously cited) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025, previously cited) and Bangs Laboratory (ProMag HP Magnetic Microspheres, retrieved from internet 07/22/2025, previously cited).
In regards to claims 1 and 8-9, Vemulapati teaches methods for separating targeting biological entities comprising one or more cellular materials (e.g., red blood cells) from a fluid sample (e.g., blood) and isolating plasma (claims 17, 31-32; paragraphs [0019, 0060]; Figs. 2-4).
In regards to step a) sub-step i), Vemulapati teaches that the method comprises obtaining a tube containing (thus, packed with) a plurality of magnetic beads (claim 23).
In regards to step a) sub-step i), Vemulapati teaches that the tube comprises an aggregation agent that aggregates the biological entities (claims 18-21; Fig. 5A).
In regards to the limitation of a “package” it is noted that the specification does not explicitly define this term. As evidenced by Merriam-Webster, most broadly, a “package” is “a covering wrapper or container”, which is how it has been interpreted throughout.
To this regard, the collection container or vessel, as taught by Vemulapati is a package as understood on the art.
However, in as much as a “package” refers to a disposable package (such as for example, a shipping package), a person of ordinary skill in the art would have been motivated to package the tube in order to maintain sterility of the tube as taught by MTC Bio (First page). Furthermore, because MTC Bio teaches that tube can be packaged (individually wrapped) (first page), it could have been done with predictable results and a reasonable expectation of success.
In regards to step b), a person of ordinary skill in the art would have been motivated to remove the packed tube from its package in order to be able to use the tube. Furthermore, because MTC bio teaches that the tube wrappers (packages) are easy to peel (first page), it could have been done with predictable results and a reasonable expectation of success.
In regards to step c), Vemulapati teaches a step of disposing the fluid sample into the packed tube (Figs. 2 and 4).
In regards to step d), Vemulapati teaches that the tube comprises a lid (Figs. 2 and 4). A person of ordinary skill in the art would have recognized that a tube lid would be capped in order to prevent contamination and reduce the likelihood of spilling the contents of the tube. Furthermore, because capping tubes with lids is standard laboratory practice, it could have been done with predictable results and a reasonable expectation of success.
In regards to a dispensing tip, Vemulapati uses a separate aspiration/dispensing needle in order to collect/dispense blood (Fig. 4A).
However, according to MPEP 2144.04(V)(B), it is prima facie obvious to make components integral (In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965) (A claim to a fluid transporting vehicle was rejected as obvious over a prior art reference which differed from the prior art in claiming a brake drum integral with a clamping means, whereas the brake disc and clamp of the prior art comprise several parts rigidly secured together as a single unit. The court affirmed the rejection holding, among other reasons, “that the use of a one-piece construction instead of the structure disclosed in [the prior art] would be merely a matter of obvious engineering choice.”).
Furthermore, tubes with integrated dispensing tips for collecting blood and plasma where known in the art before the effective filing date.
Specifically, Pennie teaches a tube for collecting blood and isolating plasma comprising a dispensing tip (claim 1; paragraphs [0025, 0045]; Figs. 2-3). Pennie also teaches that this tube comprises a filter (claim 1; paragraphs [0025, 0045]; Figs. 2-3).
A person of ordinary skill in the art would have been motivated to modify the method of Vemulapati and a tube with an integrated dispensing tip and filter, such as that as taught by Pennie because Pennie teaches that this tube is better than those used in conventional aspiration techniques because it minimizes cross-contamination of blood components in a simply more cost-effective manner (paragraphs [0002-0004]). Furthermore, because Vemulapati and Pennie are in the same technical field of using tubes to obtain blood components such as plasma, it could have been done with predictable results and a reasonable expectation of success.
In regards to step e), Vemulapati teaches that the contents of the packed tube can be mixed (agitated) (paragraphs [0012, 0086-0087, 00104]). A person of ordinary skill in the art would have recognized that this requires capping in order to avoid spilling blood or avoiding contamination.
In regards to step f), Vemulapati teaches that following mixing, the packed tube is placed in proximity of a magnetic field that separates the beads from the supernatant including the plasma (paragraphs [0020, 0062-0064]; Figs. 3, 5A-5B).
In regards to steps g) and h), while Vemulapati does not explicitly teach inverting the packed tube to bring the plasma sample in fluid and dispensing the plasma sample from the dispensing tip (i.e., filtering the plasma as it is being dispensed from the tip of the tube (see instant Fig. 4A), it would have been prima facie obvious to do so in order to remove blood components from the blood sample for further diagnosis (Fig. 3, paragraph [0069]). Furthermore, because Pennie teaches that the tubes can be inverted so that the blood product is oriented in layers and in communication with the filter for aspiration (i.e., dispensing) (paragraph [0030]; Fig. 7), and that the tube tip can serve as both inlet/outlet port (Abstract), it could have been done with predictable results and a reasonable expectation of success.
In regards the percent yield Vemulapati teaches that the method results in yields of 90% (paragraph [0166]) which overlaps with the claimed amount.
In regards to claim 4, Vemulapati teaches the supernatant can be collected for further diagnostics with suitable devices and techniques (Fig. 3, paragraph [0069]), which a person of ordinary skill in the art would have recognized suggests a further collection tube.
In regards to claim 12, Vemulapati teaches that the beads were ProMag HP, Bangs Labs beads (paragraph [00172]), which as evidenced by Bangs Laboratory, ProMag HP beads have an average diameter of 3 µm (Characteristics, first page), which is less than no larger than 4 µm.
In regards to claim 13, Vemulapati teaches that the aggregation agent is an antibody (paragraph [0048]).
In regards to claim 16, Vemulapati teaches that the supernatant is substantially free of the target biological entity.
In regards to claim 17, as above, Pennie teaches that the tube cap may comprise a filter for restricting the entry of contaminants in the chamber through the vents which is in fluid communication with the dispensing tip (claim 19; paragraph [0019]; Fig. 3). It is noted that the filter is a physical object that separates contaminants from the contents of the tube, and is therefore, a “membrane” as understood in the art. Furthermore, it is noted, that a person of ordinary skill in the art would have recognized that a filter (membrane) separates contaminates by size-exclusion due to the pore size of that filter. A person of ordinary skill in the art would have been motivated to include a filter (membrane), as taught by Pennie in order to prevent contamination. Furthermore, because Pennie teaches a filter (membrane) for a tube with a dispensing tip, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 19, Vemulapati teaches that separation and extraction can occur with a short time (e.g., within 2 min or 108 ± 21 seconds) (paragraphs [0099, 00166]; Table 1; Fig. 2), which is at least close to a timing of substantially separating within one minute as in claim 19.
According to MPEP 2144.05(I), a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985).
Furthermore, a person of ordinary skill in the art could have arrived at a timing of substantially separating within one minute as in claim 19 by routine optimization, and the disclosure does not point to a criticality in this timing.
In regards to routine optimization, according to MPEP 2144.05(II)(A), “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
In the instant case, because Vemulapati teaches that separation and extraction can occur with a short time, including ranges of times (e.g., within 2 min or 108 ± 21 seconds) (paragraphs [0099, 00166]; Table 1; Fig. 2), a person of ordinary skill in the art could have arrived at a timing of substantially separating within one minute as in claim 19 by routine optimization with predictable results and a reasonable expectation of success.
In regards to claim 20, Vemulapati teaches that the plasma purity can be greater than 99.9% (paragraph [0166]) which means that greater than 95% of the plurality of target biological entities are separated from the plasma sample.
Therefore, the combined teachings of Vemulapati, MTC Bio, and Pennie renders the invention unpatentable as claimed
Claims 2-3 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020, previously cited) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025, previously cited) and MTC Bio (ordering information, 2018, previously cited), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025, previously cited), as applied to claim 1 above, and further in view of Banfi et al. (Clin Chem Lab Med, 2007, previously cited) and Dickinson (Krackeller Scientific, retrieved from Internet Archive, archived June 24, 2022, previously cited).
In regards to claims 2-3 and 6-7, while Vemulapati teaches that the tube has an interior surface (Fig. 2), Vemulapati does not explicitly teach that the packed tube is coated at least in part with a chelation agent or anticoagulant (and thus, also contains a chelation agent or anticoagulant).
However, a person of ordinary skill in the art would have been motivated to do so because Banfi teaches that anticoagulants, including chelating agents such as EDTA, are commonly added to collection tubes in order to maintain blood in the fluid state for hematological testing or to obtain suitable plasma for coagulation and clinical chemistry analyses (Abstract, p565). They would have been motived to use tubes coated with an anticoagulant or chelation agent, because as taught by Dickinson EDTA coated blood used for whole blood hematology determinations and immunohematology testing (first page). Furthermore, because Banfi teaches that K2EDTA is the internationally recognized choice for hematological testing (Introduction, p566), and because Dickinson teaches confirms that commercial K2EDTA is the anticoagulant of choice according to international standardizations and that coated collection tubes are readily available commercially (first page), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Vemulapati, MTC Bio, Pennie, Banfi, and Dickinson renders the invention unpatentable as claimed.
Claims 5 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020, previously cited) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025, previously cited) and MTC Bio (ordering information, 2018, previously cited), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025, previously cited), as applied to claims 1 and 4 above, and further in view of Golias et al. (US4811866A, 1989, previously cited).
In regards to claims 5 and 10, in regards to a further step of squeezing the packed tube to dispense the plasma, Vemulapati teaches that the tube can be simple test tube (Fig. 2), which are well-known in the art to be made of deformable plastics. Additionally, Pennie teaches that the tube can be made out of the plastic polypropylene (paragraph [0034]) specifically, which is also is known to be deformable.
As discussed above, it would have prima facie obvious to dispense the plasma sample from the dispensing tip.
In regards to squeezing, a person of ordinary skill in the art would have been motivated to squeeze the supernatant through the tip because Golias teaches that squeezable tubes overcome problems readily encountered in the art such splashing and avoids the need for manipulative skill (Columns 1 and 2). Furthermore, because Golias (column 5) and Pennie both teach tubes can be made of polypropylene, because Golias demonstrates that biological substances can be squeezed (Fig. 5) (which also demonstrates deformability) and because Vemulapati, Pennie, and Golias are all in the same technical field of collecting biological samples in plastic tubes, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Vemulapati, MTC Bio, Pennie, and Golias renders the invention unpatentable as claimed.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020, previously cited) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025, previously cited) and MTC Bio (ordering information, 2018, previously cited), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025, previously cited), as applied to claim 1 above, and further in view of Pectu et al. (Applied Surface Science, 2015, previously cited).
In regards to claim 11, as discussed above, both Vemulapati and Pennie teach that the tube can be made out of plastic such as polypropylene, which are well-known hydrophobic materials.
Additionally, a person of ordinary skill in the art would have been motivated to specifically coat the container with a hydrophobic material because Pectu teaches that hydrophobic coatings allow for antifouling or ice repellant surfaces and promote self-cleaning (Introduction, p359). Furthermore, because Pectu teaches that plastic surfaces such as polypropylene can be coated with hydrophobic materials (Title, Abstract, p359), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Vemulapati, MTC Bio, Pennie, and Pectu renders the invention unpatentable as claimed.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020, previously cited) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025, previously cited) and MTC Bio (ordering information, 2018, previously cited), as evidenced by Merriam-Webster (retrieved from internet 07/22/2025, previously cited), as applied to claim 1 above, and further in view Zeng et al. (Thrombosis Research, 2020, previously cited).
In regards to claim 14, it is noted that the claim is unlimited in regards to the aggregation agent, but only states that any aggregation agent can be present at a concentration from about 3mg/mL to about 5mg/mL.
Turning to the art, Vemulapati teaches that a concentration of about 3.5µg/mL of aggregation agent is sufficient to obtain plasma of high purity (greater than 99%) (paragraph [00168]).
While less than a concentration of about 3mg/mL to about 5mg/mL, again it is noted that that the claim does not require any particular aggregation agent, and a person of ordinary skill in the art would have realized that concentrations are dependent on the specific compound being used.
Additionally, a person of ordinary skill in the art could have arrived at a concentration of about 3mg/mL to about 5mg/mL by routine optimization, the disclosure does not point to a criticality in this concentration range (see MPEP 2144.05(II)(A), as discussed above).
Furthermore, because as taught by Zeng, increasing concentrations of fibrinogen to 5 mg/mL increases clot strength in blood samples (Abstract, p48), which overlaps with the range of about 3mg/mL to about 5mg/mL, a concentration range of about 3mg/mL to about 5mg/mL could have been arrived at by routine optimization with predictable results and a reasonable expectation of success.
Moreover, a person of ordinary skill in the art would have been motivated to use a concentration of 5 mg/mL because Zeng indicates that this results in increased clot turbidity and increased clot strength for multiple species compared to lower concentrations when using fibrinogen (Abstract, p48). Furthermore, because Vemulapati specifically lists fibrinogen as a possible aggregation agent (paragraph [00196]), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Vemulapati, MTC Bio, Pennie, and Pectu renders the invention unpatentable as claimed.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020, previously cited) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025, previously cited) and MTC Bio (ordering information, 2018, previously cited) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025, previously cited), as applied to claim 1 above, and further in view of Murto et al. (US6689615B1, on IDS 06/12/2025, previously cited).
In regards to claim 15, Vemulapati teaches that magnetic beads and aggregation agent (antibodies) were tried together in the tube (claim 26; paragraph [00172], but is silent as to whether the magnetic beads and aggregation agents were lyophilized specifically. However, a person of ordinary skill in the art would have been motivated to do so because Murto teaches that lyophilized particles resuspend quicker relative to other dried preparations (claim 32; example 6, paragraphs 19-20; Table 3). Furthermore, because Murto teaches lyophilization techniques (claim 32; example 6, paragraphs 19-20; Table 3), and because Vemulapati and Murto are in the same technical field of separating biological components using magnetic beads, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Vemulapati, MTC Bio, Pennie, and Murto renders the invention unpatentable as claimed.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Vemulapati et al. (WO2020019001A1, 2020, previously cited) in view of Pennie (US20160367982A1, 2008, on IDS 06/12/2025, previously cited) and MTC Bio (ordering information, 2018, previously cited) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025, previously cited), as applied to claim 1 above, and further in view of Cassaday et al. (US4602995, on IDS 06/12/2025).
In regards to claim 21, in regards to the limitation of “wherein the dispensing tip dispenses a pre-determined amount of plasma sample”, it is noted that the claim is broad and does not require any specific amount. Indeed, subjecting a tube comprising a dispensing tip with a given dimension with the same dispensing force would result in the dispensing of the same amount (and therefore, a uniform amount) of plasma sample. Furthermore, as taught by Cassaday, aspirating probe length (i.e. tip length) can be changed to control the precisely repeatable level of blood serum for sample analysis (column 8, lines 50-59; Fig. 5). A person of ordinary skill in the art would have been motivated to set a specific tip length to a particular length so that repeated samples are uniform for further diagnostics. Furthermore, because Cassaday teaches that tip length can be changed to control serum levels for sample analysis, and furthermore, teaches generally a similar cap (lid) to be used with tubes for collecting blood samples and separating those blood samples into their components, including plasma (Abstract; columns 1 and 2; claim 1; Fig. 5), and because Vemulapati, Pennie, and Cassaday are all in the same technical field of utilizing tubes for collection of blood and obtaining serum, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Vemulapati, MTC Bio, Pennie, and Cassaday renders the invention unpatentable as claimed.
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 1, 4, 8-9, 12-14, 16-17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,216,116 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025).
Claims 2-3 and 6-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,216,116 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Banfi et al. (Clin Chem Lab Med, 2007, previously cited) and Dickinson (Krackeller Scientific, retrieved from Internet Archive, archived June 24, 2022, previously cited).
Claims 5 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,216,116 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Golias et al. (US4811866A, 1989, previously cited).
Claim 13 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,216,116 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Pectu et al. (Applied Surface Science, 2015, previously cited).
Claim 15 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,216,116 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Zeng et al. (Thrombosis Research, 2020, previously cited).
Claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,216,116 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Murto et al. (US6689615B1, on IDS 06/12/2025, previously cited).
While the instant claims and claims 1-21 of U.S. Patent No. 12,216,116 are not the same, they are not patentably distinct because the claims of both inventions are drawn to systems that utilize a vessel (package) comprising a tube containing (packed with) magnetic beads, an aggregation agent (that can overlaps with the range of about 3mg/ml to about 5 mg/mL), and a fluid biological sample (blood) which is exposed to a magnetic force in to agitate (mix) the components of the tube in order to obtain a biological entity (of which serum, a component of blood is a type).
In regards to the limitation of a “package” it is noted that the specification does not explicitly define this term. As evidenced by Merriam-Webster, most broadly, a “package” is “a covering wrapper or container”, which is how it has been interpreted throughout.
To this regard, the collection container or vessel, as claimed by U.S. Patent No. 12,216,116 is a package as understood on the art.
However, in as much as a “package” refers to a disposable package (such as for example, a shipping package), a person of ordinary skill in the art would have been motivated to package the tube in order to maintain sterility of the tube as taught by MTC Bio (First page). Furthermore, because MTC Bio teaches that tube can be packaged (individually wrapped) (first page), it could have been done with predictable results and a reasonable expectation of success. Additionally, it would have been predicably obvious to
In regards to the design of the tube, U.S. Patent No. 12,216,116 is silent as to these limitations.
However, Vemulapati teaches methods for separating targeting biological entities comprising one or more cellular materials (e.g., red blood cells) from a fluid sample (e.g., blood) and isolating plasma (claims 17, 31-32; paragraphs [0019, 0060]; Figs. 2-4). Vemulapati teaches that the method results in yields of 90% (paragraph [0166]) which overlaps with the claimed amount. Vemulapati teaches that the method comprises obtaining a tube containing (thus, packed with) a plurality of magnetic beads (claim 23) and that the tube comprises an aggregation agent that aggregates the biological entities (claims 18-21; Fig. 5A).
Furthermore, Vemulapati teaches a step of disposing the fluid sample into the packed tube (Figs. 2 and 4) and Vemulapati teaches that the tube comprises a lid (Figs. 2 and 4). A person of ordinary skill in the art would have recognized that a tube lid would be capped in order to prevent contamination and reduce the likelihood of spilling the contents of the tube. Furthermore, because capping tubes with lids is standard laboratory practice, it could have been done with predictable results and a reasonable expectation of success.
In regards to a dispensing tip, Vemulapati uses a separate aspiration/dispensing needle in order to collect/dispense blood (Fig. 4A).
However, according to MPEP 2144.04(V)(B), it is prima facie obvious to make components integral (In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965) (A claim to a fluid transporting vehicle was rejected as obvious over a prior art reference which differed from the prior art in claiming a brake drum integral with a clamping means, whereas the brake disc and clamp of the prior art comprise several parts rigidly secured together as a single unit. The court affirmed the rejection holding, among other reasons, “that the use of a one-piece construction instead of the structure disclosed in [the prior art] would be merely a matter of obvious engineering choice.”).
Furthermore, tubes with integrated dispensing tips for collecting blood and plasma where known in the art before the effective filing date.
Specifically, Pennie teaches a tube for collecting blood and isolating plasma comprising a dispensing tip (claim 1; paragraphs [0025, 0045]; Figs. 2-3). Pennie also teaches that this tube comprises a filter (claim 1; paragraphs [0025, 0045]; Figs. 2-3).
A person of ordinary skill in the art would have been motivated to modify the method of Vemulapati and a tube with an integrated dispensing tip and filter, such as that as taught by Pennie because Pennie teaches that this tube is better than those used in conventional aspiration techniques because it minimizes cross-contamination of blood components in a simply more cost-effective manner (paragraphs [0002-0004]). Furthermore, because Vemulapati and Pennie are in the same technical field of using tubes to obtain blood components such as plasma, it could have been done with predictable results and a reasonable expectation of success.
In regards to inverting the packed tube to bring the plasma sample in fluid and dispensing the plasma sample from the dispensing tip (i.e., filtering the plasma as it is being dispensed from the tip of the tube (see instant Fig. 4A), it would have been prima facie obvious to do so in order to remove blood components from the blood sample for further diagnosis (Fig. 3, paragraph [0069]). Furthermore, because Pennie teaches that the tubes can be inverted so that the blood product is oriented in layers and in communication with the filter for aspiration (i.e., dispensing) (paragraph [0030]; Fig. 7), and that the tube tip can serve as both inlet/outlet port (Abstract), it could have been done with predictable results and a reasonable expectation of success.
Furthermore, the embodiments of the dependent claims were also known in the prior art before the effective filing date.
Specifically, in regards to claims 2-3 and 6-7, a person of ordinary skill in the art would have been motivated to do so because Banfi teaches that anticoagulants, including chelating agents such as EDTA, are commonly added to collection tubes in order to maintain blood in the fluid state for hematological testing or to obtain suitable plasma for coagulation and clinical chemistry analyses (Abstract, p565). They would have been motived to use tubes coated with an anticoagulant or chelation agent, because as taught by Dickinson EDTA coated blood used for whole blood hematology determinations and immunohematology testing (first page). Furthermore, because Banfi teaches that K2EDTA is the internationally recognized choice for hematological testing (Introduction, p566), and because Dickinson teaches confirms that commercial K2EDTA is the anticoagulant of choice according to international standardizations and that coated collection tubes are readily available commercially (first page), it could have been done with predictable results and a reasonable expectation of success.
Additionally, regards to claims 5 and 10, in regards to a further step of squeezing the packed tube to dispense the plasma, Vemulapati teaches that the tube can be simple test tube (Fig. 2), which are well-known in the art to be made of deformable plastics. Additionally, Pennie teaches that the tube can be made out of the plastic polypropylene (paragraph [0034]) specifically, which is also is known to be deformable.
As discussed above, it would have prima facie obvious to dispense the plasma sample from the dispensing tip.
In regards to squeezing, a person of ordinary skill in the art would have been motivated to squeeze the supernatant through the tip because Golias teaches that squeezable tubes overcome problems readily encountered in the art such splashing and avoids the need for manipulative skill (Columns 1 and 2). Furthermore, because Golias (column 5) and Pennie both teach tubes can be made of polypropylene, because Golias demonstrates that biological substances can be squeezed (Fig. 5) (which also demonstrates deformability) and because Vemulapati, Pennie, and Golias are all in the same technical field of collecting biological samples in plastic tubes, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 11, as discussed above, both Vemulapati and Pennie teach that the tube can be made out of plastic such as polypropylene, which are well-known hydrophobic materials.
Additionally, a person of ordinary skill in the art would have been motivated to specifically coat the container with a hydrophobic material because Pectu teaches that hydrophobic coatings allow for antifouling or ice repellant surfaces and promote self-cleaning (Introduction, p359). Furthermore, because Pectu teaches that plastic surfaces such as polypropylene can be coated with hydrophobic materials (Title, Abstract, p359), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 15, a person of ordinary skill in the art would have been motivated to do so because Murto teaches that lyophilized particles resuspend quicker relative to other dried preparations (claim 32; example 6, paragraphs 19-20; Table 3). Furthermore, because Murto teaches lyophilization techniques (claim 32; example 6, paragraphs 19-20; Table 3), and because Vemulapati and Murto are in the same technical field of separating biological components using magnetic beads, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 21, in regards to the limitation of “wherein the dispensing tip dispenses a pre-determined amount of plasma sample”, it is noted that the claim is broad and does not require any specific amount. Indeed, subjecting a tube comprising a dispensing tip with a given dimension with the same dispensing force would result in the dispensing of the same amount (and therefore, a uniform amount) of plasma sample. Furthermore, as taught by Cassaday, aspirating probe length (i.e. tip length) can be changed to control the precisely repeatable level of blood serum for sample analysis (column 8, lines 50-59; Fig. 5). A person of ordinary skill in the art would have been motivated to set a specific tip length to a particular length so that repeated samples are uniform for further diagnostics. Furthermore, because Cassaday teaches that tip length can be changed to control serum levels for sample analysis, and furthermore, teaches generally a similar cap (lid) to be used with tubes for collecting blood samples and separating those blood samples into their components, including plasma (Abstract; columns 1 and 2; claim 1; Fig. 5), and because Vemulapati, Pennie, and Cassaday are all in the same technical field of utilizing tubes for collection of blood and obtaining serum, it could have been done with predictable results and a reasonable expectation of success.
Claims 1, 4, 8-9, 12-13, 16-17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,262,352 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025).
Claims 2-3 and 6-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,262,352 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Banfi et al. (Clin Chem Lab Med, 2007, previously cited) and Dickinson (Krackeller Scientific, retrieved from Internet Archive, archived June 24, 2022, previously cited).
Claims 5 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,262,352 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Golias et al. (US4811866A, 1989, previously cited).
Claim 13 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,262,352 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Pectu et al. (Applied Surface Science, 2015, previously cited).
Claim 14 is ejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,262,352 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Zeng et al. (Thrombosis Research, 2020, previously cited).
Claim 15 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,262,352 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Zeng et al. (Thrombosis Research, 2020, previously cited).
Claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,262,352 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Murto et al. (US6689615B1, on IDS 06/12/2025, previously cited).
While the instant claims and 1-26 of U.S. Patent No. 11,262,352 are not the same, they are not patentably distinct because the claims of both inventions are drawn to systems and methods that utilize a vessel (package) comprising a tube containing (packed with) magnetic beads, an aggregation agent, and a fluid biological sample which is exposed to a magnetic force. A person of ordinary skill in the art would have recognized that exposing a tube with magnetic beads to a magnetic force would cause agitation of the contents of the tube.
In regards to the limitation of a “package” it is noted that the specification does not explicitly define this term. As evidenced by Merriam-Webster, most broadly, a “package” is “a covering wrapper or container”, which is how it has been interpreted throughout.
To this regard, the collection container or vessel, as claimed by U.S. Patent No. 12,216,116 is a package as understood on the art.
However, in as much as a “package” refers to a disposable package (such as for example, a shipping package), a person of ordinary skill in the art would have been motivated to package the tube in order to maintain sterility of the tube as taught by MTC Bio (First page). Furthermore, because MTC Bio teaches that tube can be packaged (individually wrapped) (first page), it could have been done with predictable results and a reasonable expectation of success. Additionally, it would have been predicably obvious to
In regards to the design of the tube, U.S. Patent No. 12,216,116 is silent as to these limitations.
However, Vemulapati teaches methods for separating targeting biological entities comprising one or more cellular materials (e.g., red blood cells) from a fluid sample (e.g., blood) and isolating plasma (claims 17, 31-32; paragraphs [0019, 0060]; Figs. 2-4). Vemulapati teaches that the method results in yields of 90% (paragraph [0166]) which overlaps with the claimed amount. Vemulapati teaches that the method comprises obtaining a tube containing (thus, packed with) a plurality of magnetic beads (claim 23) and that the tube comprises an aggregation agent that aggregates the biological entities (claims 18-21; Fig. 5A).
Furthermore, Vemulapati teaches a step of disposing the fluid sample into the packed tube (Figs. 2 and 4) and Vemulapati teaches that the tube comprises a lid (Figs. 2 and 4). A person of ordinary skill in the art would have recognized that a tube lid would be capped in order to prevent contamination and reduce the likelihood of spilling the contents of the tube. Furthermore, because capping tubes with lids is standard laboratory practice, it could have been done with predictable results and a reasonable expectation of success.
In regards to a dispensing tip, Vemulapati uses a separate aspiration/dispensing needle in order to collect/dispense blood (Fig. 4A).
However, according to MPEP 2144.04(V)(B), it is prima facie obvious to make components integral (In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965) (A claim to a fluid transporting vehicle was rejected as obvious over a prior art reference which differed from the prior art in claiming a brake drum integral with a clamping means, whereas the brake disc and clamp of the prior art comprise several parts rigidly secured together as a single unit. The court affirmed the rejection holding, among other reasons, “that the use of a one-piece construction instead of the structure disclosed in [the prior art] would be merely a matter of obvious engineering choice.”).
Furthermore, tubes with integrated dispensing tips for collecting blood and plasma where known in the art before the effective filing date.
Specifically, Pennie teaches a tube for collecting blood and isolating plasma comprising a dispensing tip (claim 1; paragraphs [0025, 0045]; Figs. 2-3). Pennie also teaches that this tube comprises a filter (claim 1; paragraphs [0025, 0045]; Figs. 2-3).
A person of ordinary skill in the art would have been motivated to modify the method of Vemulapati and a tube with an integrated dispensing tip and filter, such as that as taught by Pennie because Pennie teaches that this tube is better than those used in conventional aspiration techniques because it minimizes cross-contamination of blood components in a simply more cost-effective manner (paragraphs [0002-0004]). Furthermore, because Vemulapati and Pennie are in the same technical field of using tubes to obtain blood components such as plasma, it could have been done with predictable results and a reasonable expectation of success.
In regards to inverting the packed tube to bring the plasma sample in fluid and dispensing the plasma sample from the dispensing tip (i.e., filtering the plasma as it is being dispensed from the tip of the tube (see instant Fig. 4A), it would have been prima facie obvious to do so in order to remove blood components from the blood sample for further diagnosis (Fig. 3, paragraph [0069]). Furthermore, because Pennie teaches that the tubes can be inverted so that the blood product is oriented in layers and in communication with the filter for aspiration (i.e., dispensing) (paragraph [0030]; Fig. 7), and that the tube tip can serve as both inlet/outlet port (Abstract), it could have been done with predictable results and a reasonable expectation of success.
Furthermore, the embodiments of the dependent claims were also known in the prior art before the effective filing date.
Specifically, in regards to claims 2-3 and 6-7, a person of ordinary skill in the art would have been motivated to do so because Banfi teaches that anticoagulants, including chelating agents such as EDTA, are commonly added to collection tubes in order to maintain blood in the fluid state for hematological testing or to obtain suitable plasma for coagulation and clinical chemistry analyses (Abstract, p565). They would have been motived to use tubes coated with an anticoagulant or chelation agent, because as taught by Dickinson EDTA coated blood used for whole blood hematology determinations and immunohematology testing (first page). Furthermore, because Banfi teaches that K2EDTA is the internationally recognized choice for hematological testing (Introduction, p566), and because Dickinson teaches confirms that commercial K2EDTA is the anticoagulant of choice according to international standardizations and that coated collection tubes are readily available commercially (first page), it could have been done with predictable results and a reasonable expectation of success.
Additionally, regards to claims 5 and 10, in regards to a further step of squeezing the packed tube to dispense the plasma, Vemulapati teaches that the tube can be simple test tube (Fig. 2), which are well-known in the art to be made of deformable plastics. Additionally, Pennie teaches that the tube can be made out of the plastic polypropylene (paragraph [0034]) specifically, which is also is known to be deformable.
As discussed above, it would have prima facie obvious to dispense the plasma sample from the dispensing tip.
In regards to squeezing, a person of ordinary skill in the art would have been motivated to squeeze the supernatant through the tip because Golias teaches that squeezable tubes overcome problems readily encountered in the art such splashing and avoids the need for manipulative skill (Columns 1 and 2). Furthermore, because Golias (column 5) and Pennie both teach tubes can be made of polypropylene, because Golias demonstrates that biological substances can be squeezed (Fig. 5) (which also demonstrates deformability) and because Vemulapati, Pennie, and Golias are all in the same technical field of collecting biological samples in plastic tubes, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 11, as discussed above, both Vemulapati and Pennie teach that the tube can be made out of plastic such as polypropylene, which are well-known hydrophobic materials.
Additionally, a person of ordinary skill in the art would have been motivated to specifically coat the container with a hydrophobic material because Pectu teaches that hydrophobic coatings allow for antifouling or ice repellant surfaces and promote self-cleaning (Introduction, p359). Furthermore, because Pectu teaches that plastic surfaces such as polypropylene can be coated with hydrophobic materials (Title, Abstract, p359), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 14, Vemulapati teaches that a concentration of about 3.5µg/mL of aggregation agent is sufficient to obtain plasma of high purity (greater than 99%) (paragraph [00168]).
While less than a concentration of about 3mg/mL to about 5mg/mL, again it is noted that that the claim does not require any particular aggregation agent, and a person of ordinary skill in the art would have realized that concentrations are dependent on the specific compound being used.
Additionally, a person of ordinary skill in the art could have arrived at a concentration of about 3mg/mL to about 5mg/mL by routine optimization, the disclosure does not point to a criticality in this concentration range (see MPEP 2144.05(II)(A), as discussed above).
Furthermore, because as taught by Zeng, increasing concentrations of fibrinogen to 5 mg/mL increases clot strength in blood samples (Abstract, p48), which overlaps with the range of about 3mg/mL to about 5mg/mL, a concentration range of about 3mg/mL to about 5mg/mL could have been arrived at by routine optimization with predictable results and a reasonable expectation of success.
Moreover, a person of ordinary skill in the art would have been motivated to use a concentration of 5 mg/mL because Zeng indicates that this results in increased clot turbidity and increased clot strength for multiple species compared to lower concentrations when using fibrinogen (Abstract, p48). Furthermore, because Vemulapati specifically lists fibrinogen as a possible aggregation agent (paragraph [00196]), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 15, a person of ordinary skill in the art would have been motivated to do so because Murto teaches that lyophilized particles resuspend quicker relative to other dried preparations (claim 32; example 6, paragraphs 19-20; Table 3). Furthermore, because Murto teaches lyophilization techniques (claim 32; example 6, paragraphs 19-20; Table 3), and because Vemulapati and Murto are in the same technical field of separating biological components using magnetic beads, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 21, in regards to the limitation of “wherein the dispensing tip dispenses a pre-determined amount of plasma sample”, it is noted that the claim is broad and does not require any specific amount. Indeed, subjecting a tube comprising a dispensing tip with a given dimension with the same dispensing force would result in the dispensing of the same amount (and therefore, a uniform amount) of plasma sample. Furthermore, as taught by Cassaday, aspirating probe length (i.e. tip length) can be changed to control the precisely repeatable level of blood serum for sample analysis (column 8, lines 50-59; Fig. 5). A person of ordinary skill in the art would have been motivated to set a specific tip length to a particular length so that repeated samples are uniform for further diagnostics. Furthermore, because Cassaday teaches that tip length can be changed to control serum levels for sample analysis, and furthermore, teaches generally a similar cap (lid) to be used with tubes for collecting blood samples and separating those blood samples into their components, including plasma (Abstract; columns 1 and 2; claim 1; Fig. 5), and because Vemulapati, Pennie, and Cassaday are all in the same technical field of utilizing tubes for collection of blood and obtaining serum, it could have been done with predictable results and a reasonable expectation of success.
Claims 1, 4, 8-9, 12-13, 16-17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/024,319 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025) and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025).
Claims 2-3 and 6-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/024,319 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Banfi et al. (Clin Chem Lab Med, 2007, previously cited) and Dickinson (Krackeller Scientific, retrieved from Internet Archive, archived June 24, 2022, previously cited).
Claims 5 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/024,319 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Golias et al. (US4811866A, 1989, previously cited).
Claim 13 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/024,319 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Pectu et al. (Applied Surface Science, 2015, previously cited).
Claim 14 is ejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/024,319 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Zeng et al. (Thrombosis Research, 2020, previously cited).
Claim 15 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/024,319 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Zeng et al. (Thrombosis Research, 2020, previously cited).
Claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/024,319 in view of Vemulapati et al. (WO2020019001A1, 2020, previously cited), Pennie (US20160367982A1, 2008, on IDS 06/12/2025), and MTC Bio (ordering information, 2018) as evidenced by Merriam-Webster (retrieved from internet 07/22/2025) as applied to claim 1 above, and further in view of Murto et al. (US6689615B1, on IDS 06/12/2025, previously cited).
While the instant claims and claims 1-20 of copending Application No. 19/024,319 are not the same, they are not patentably distinct because the claims of both inventions are drawn to systems that utilize a vessel (package) comprising a tube containing (packed with) magnetic beads, an aggregation agent, and a fluid biological sample (blood) which is exposed to a magnetic force. A person of ordinary skill in the art would have recognized that exposing a tube with magnetic beads to a magnetic force would cause agitation of the contents of the tube.
In regards to the limitation of a “package” it is noted that the specification does not explicitly define this term. As evidenced by Merriam-Webster, most broadly, a “package” is “a covering wrapper or container”, which is how it has been interpreted throughout.
To this regard, the collection container or vessel, as claimed by copending Application No. 19/024,319 is a package as understood on the art.
However, in as much as a “package” refers to a disposable package (such as for example, a shipping package), a person of ordinary skill in the art would have been motivated to package the tube in order to maintain sterility of the tube as taught by MTC Bio (First page). Furthermore, because MTC Bio teaches that tube can be packaged (individually wrapped) (first page), it could have been done with predictable results and a reasonable expectation of success.
In regards to the design of the tube, copending Application No. 19/024,319 is silent as to these limitations.
While the instant claims and 1-26 of U.S. Patent No. 11,262,352 are not the same, they are not patentably distinct because the claims of both inventions are drawn to systems and methods that utilize a vessel (package) comprising a tube containing (packed with) magnetic beads, an aggregation agent, and a fluid biological sample which is exposed to a magnetic force. A person of ordinary skill in the art would have recognized that exposing a tube with magnetic beads to a magnetic force would cause agitation of the contents of the tube.
In regards to the limitation of a “package” it is noted that the specification does not explicitly define this term. As evidenced by Merriam-Webster, most broadly, a “package” is “a covering wrapper or container”, which is how it has been interpreted throughout.
To this regard, the collection container or vessel, as claimed by U.S. Patent No. 12,216,116 is a package as understood on the art.
However, in as much as a “package” refers to a disposable package (such as for example, a shipping package), a person of ordinary skill in the art would have been motivated to package the tube in order to maintain sterility of the tube as taught by MTC Bio (First page). Furthermore, because MTC Bio teaches that tube can be packaged (individually wrapped) (first page), it could have been done with predictable results and a reasonable expectation of success. Additionally, it would have been predicably obvious to
In regards to the design of the tube, U.S. Patent No. 12,216,116 is silent as to these limitations.
However, Vemulapati teaches methods for separating targeting biological entities comprising one or more cellular materials (e.g., red blood cells) from a fluid sample (e.g., blood) and isolating plasma (claims 17, 31-32; paragraphs [0019, 0060]; Figs. 2-4). Vemulapati teaches that the method results in yields of 90% (paragraph [0166]) which overlaps with the claimed amount. Vemulapati teaches that the method comprises obtaining a tube containing (thus, packed with) a plurality of magnetic beads (claim 23) and that the tube comprises an aggregation agent that aggregates the biological entities (claims 18-21; Fig. 5A).
Furthermore, Vemulapati teaches a step of disposing the fluid sample into the packed tube (Figs. 2 and 4) and Vemulapati teaches that the tube comprises a lid (Figs. 2 and 4). A person of ordinary skill in the art would have recognized that a tube lid would be capped in order to prevent contamination and reduce the likelihood of spilling the contents of the tube. Furthermore, because capping tubes with lids is standard laboratory practice, it could have been done with predictable results and a reasonable expectation of success.
In regards to a dispensing tip, Vemulapati uses a separate aspiration/dispensing needle in order to collect/dispense blood (Fig. 4A).
However, according to MPEP 2144.04(V)(B), it is prima facie obvious to make components integral (In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965) (A claim to a fluid transporting vehicle was rejected as obvious over a prior art reference which differed from the prior art in claiming a brake drum integral with a clamping means, whereas the brake disc and clamp of the prior art comprise several parts rigidly secured together as a single unit. The court affirmed the rejection holding, among other reasons, “that the use of a one-piece construction instead of the structure disclosed in [the prior art] would be merely a matter of obvious engineering choice.”).
Furthermore, tubes with integrated dispensing tips for collecting blood and plasma where known in the art before the effective filing date.
Specifically, Pennie teaches a tube for collecting blood and isolating plasma comprising a dispensing tip (claim 1; paragraphs [0025, 0045]; Figs. 2-3). Pennie also teaches that this tube comprises a filter (claim 1; paragraphs [0025, 0045]; Figs. 2-3).
A person of ordinary skill in the art would have been motivated to modify the method of Vemulapati and a tube with an integrated dispensing tip and filter, such as that as taught by Pennie because Pennie teaches that this tube is better than those used in conventional aspiration techniques because it minimizes cross-contamination of blood components in a simply more cost-effective manner (paragraphs [0002-0004]). Furthermore, because Vemulapati and Pennie are in the same technical field of using tubes to obtain blood components such as plasma, it could have been done with predictable results and a reasonable expectation of success.
In regards to inverting the packed tube to bring the plasma sample in fluid and dispensing the plasma sample from the dispensing tip (i.e., filtering the plasma as it is being dispensed from the tip of the tube (see instant Fig. 4A), it would have been prima facie obvious to do so in order to remove blood components from the blood sample for further diagnosis (Fig. 3, paragraph [0069]). Furthermore, because Pennie teaches that the tubes can be inverted so that the blood product is oriented in layers and in communication with the filter for aspiration (i.e., dispensing) (paragraph [0030]; Fig. 7), and that the tube tip can serve as both inlet/outlet port (Abstract), it could have been done with predictable results and a reasonable expectation of success.
Furthermore, the embodiments of the dependent claims were also known in the prior art before the effective filing date.
Specifically, in regards to claims 2-3 and 6-7, a person of ordinary skill in the art would have been motivated to do so because Banfi teaches that anticoagulants, including chelating agents such as EDTA, are commonly added to collection tubes in order to maintain blood in the fluid state for hematological testing or to obtain suitable plasma for coagulation and clinical chemistry analyses (Abstract, p565). They would have been motived to use tubes coated with an anticoagulant or chelation agent, because as taught by Dickinson EDTA coated blood used for whole blood hematology determinations and immunohematology testing (first page). Furthermore, because Banfi teaches that K2EDTA is the internationally recognized choice for hematological testing (Introduction, p566), and because Dickinson teaches confirms that commercial K2EDTA is the anticoagulant of choice according to international standardizations and that coated collection tubes are readily available commercially (first page), it could have been done with predictable results and a reasonable expectation of success.
Additionally, regards to claims 5 and 10, in regards to a further step of squeezing the packed tube to dispense the plasma, Vemulapati teaches that the tube can be simple test tube (Fig. 2), which are well-known in the art to be made of deformable plastics. Additionally, Pennie teaches that the tube can be made out of the plastic polypropylene (paragraph [0034]) specifically, which is also is known to be deformable.
As discussed above, it would have prima facie obvious to dispense the plasma sample from the dispensing tip.
In regards to squeezing, a person of ordinary skill in the art would have been motivated to squeeze the supernatant through the tip because Golias teaches that squeezable tubes overcome problems readily encountered in the art such splashing and avoids the need for manipulative skill (Columns 1 and 2). Furthermore, because Golias (column 5) and Pennie both teach tubes can be made of polypropylene, because Golias demonstrates that biological substances can be squeezed (Fig. 5) (which also demonstrates deformability) and because Vemulapati, Pennie, and Golias are all in the same technical field of collecting biological samples in plastic tubes, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 11, as discussed above, both Vemulapati and Pennie teach that the tube can be made out of plastic such as polypropylene, which are well-known hydrophobic materials.
Additionally, a person of ordinary skill in the art would have been motivated to specifically coat the container with a hydrophobic material because Pectu teaches that hydrophobic coatings allow for antifouling or ice repellant surfaces and promote self-cleaning (Introduction, p359). Furthermore, because Pectu teaches that plastic surfaces such as polypropylene can be coated with hydrophobic materials (Title, Abstract, p359), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 14, Vemulapati teaches that a concentration of about 3.5µg/mL of aggregation agent is sufficient to obtain plasma of high purity (greater than 99%) (paragraph [00168]).
While less than a concentration of about 3mg/mL to about 5mg/mL, again it is noted that that the claim does not require any particular aggregation agent, and a person of ordinary skill in the art would have realized that concentrations are dependent on the specific compound being used.
Additionally, a person of ordinary skill in the art could have arrived at a concentration of about 3mg/mL to about 5mg/mL by routine optimization, the disclosure does not point to a criticality in this concentration range (see MPEP 2144.05(II)(A), as discussed above).
Furthermore, because as taught by Zeng, increasing concentrations of fibrinogen to 5 mg/mL increases clot strength in blood samples (Abstract, p48), which overlaps with the range of about 3mg/mL to about 5mg/mL, a concentration range of about 3mg/mL to about 5mg/mL could have been arrived at by routine optimization with predictable results and a reasonable expectation of success.
Moreover, a person of ordinary skill in the art would have been motivated to use a concentration of 5 mg/mL because Zeng indicates that this results in increased clot turbidity and increased clot strength for multiple species compared to lower concentrations when using fibrinogen (Abstract, p48). Furthermore, because Vemulapati specifically lists fibrinogen as a possible aggregation agent (paragraph [00196]), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 15, a person of ordinary skill in the art would have been motivated to do so because Murto teaches that lyophilized particles resuspend quicker relative to other dried preparations (claim 32; example 6, paragraphs 19-20; Table 3). Furthermore, because Murto teaches lyophilization techniques (claim 32; example 6, paragraphs 19-20; Table 3), and because Vemulapati and Murto are in the same technical field of separating biological components using magnetic beads, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 21, in regards to the limitation of “wherein the dispensing tip dispenses a pre-determined amount of plasma sample”, it is noted that the claim is broad and does not require any specific amount. Indeed, subjecting a tube comprising a dispensing tip with a given dimension with the same dispensing force would result in the dispensing of the same amount (and therefore, a uniform amount) of plasma sample. Furthermore, as taught by Cassaday, aspirating probe length (i.e. tip length) can be changed to control the precisely repeatable level of blood serum for sample analysis (column 8, lines 50-59; Fig. 5). A person of ordinary skill in the art would have been motivated to set a specific tip length to a particular length so that repeated samples are uniform for further diagnostics. Furthermore, because Cassaday teaches that tip length can be changed to control serum levels for sample analysis, and furthermore, teaches generally a similar cap (lid) to be used with tubes for collecting blood samples and separating those blood samples into their components, including plasma (Abstract; columns 1 and 2; claim 1; Fig. 5), and because Vemulapati, Pennie, and Cassaday are all in the same technical field of utilizing tubes for collection of blood and obtaining serum, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant argues that that the combined teachings of Vemulapati, Pennie, and MTC are not prima facie obvious over the claimed as amended, pointing specifically to steps d) through h) (Remarks, p6-7).
Applicant’s arguments filed 03/13/2026 have been fully considered but are not found persuasive. All of the claimed features of claim 1 as amended are prima facie obvious as discussed above.
Specifically, as discussed above, in regards to step d), Vemulapati teaches that the tube comprises a lid (Figs. 2 and 4). A person of ordinary skill in the art would have recognized that a tube lid would be capped in order to prevent contamination and reduce the likelihood of spilling the contents of the tube. Furthermore, because capping tubes with lids is standard laboratory practice, it could have been done with predictable results and a reasonable expectation of success.
In regards to a dispensing tip, Vemulapati uses a separate aspiration/dispensing needle in order to collect/dispense blood (Fig. 4A).
However, according to MPEP 2144.04(V)(B), it is prima facie obvious to make components integral (In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965) (A claim to a fluid transporting vehicle was rejected as obvious over a prior art reference which differed from the prior art in claiming a brake drum integral with a clamping means, whereas the brake disc and clamp of the prior art comprise several parts rigidly secured together as a single unit. The court affirmed the rejection holding, among other reasons, “that the use of a one-piece construction instead of the structure disclosed in [the prior art] would be merely a matter of obvious engineering choice.”).
Furthermore, tubes with integrated dispensing tips for collecting blood and plasma where known in the art before the effective filing date.
Specifically, Pennie teaches a tube for collecting blood and isolating plasma comprising a dispensing tip (claim 1; paragraphs [0025, 0045]; Figs. 2-3). Pennie also teaches that this tube comprises a filter (claim 1; paragraphs [0025, 0045]; Figs. 2-3).
A person of ordinary skill in the art would have been motivated to modify the method of Vemulapati and a tube with an integrated dispensing tip and filter, such as that as taught by Pennie because Pennie teaches that this tube is better than those used in conventional aspiration techniques because it minimizes cross-contamination of blood components in a simply more cost-effective manner (paragraphs [0002-0004]). Furthermore, because Vemulapati and Pennie are in the same technical field of using tubes to obtain blood components such as plasma, it could have been done with predictable results and a reasonable expectation of success.
In regards to step e), Vemulapati teaches that the contents of the packed tube can be mixed (agitated) (paragraphs [0012, 0086-0087, 00104]). A person of ordinary skill in the art would have recognized that this requires capping in order to avoid spilling blood or avoiding contamination.
In regards to step f), Vemulapati teaches that following mixing, the packed tube is placed in proximity of a magnetic field that separates the beads from the supernatant including the plasma (paragraphs [0020, 0062-0064]; Figs. 3, 5A-5B).
In regards to steps g) and h), while Vemulapati does not explicitly teach inverting the packed tube to bring the plasma sample in fluid and dispensing the plasma sample from the dispensing tip (i.e., filtering the plasma as it is being dispensed from the tip of the tube (see instant Fig. 4A), it would have been prima facie obvious to do so in order to remove blood components from the blood sample for further diagnosis (Fig. 3, paragraph [0069]). Furthermore, because Pennie teaches that the tubes can be inverted so that the blood product is oriented in layers and in communication with the filter for aspiration (i.e., dispensing) (paragraph [0030]; Fig. 7), and that the tube tip can serve as both inlet/outlet port (Abstract), it could have been done with predictable results and a reasonable expectation of success.
In regards the percent yield Vemulapati teaches that the method results in yields of 90% (paragraph [0166]) which overlaps with the claimed amount.
Applicant argues that none of the Banfi, Dickinson, Golias, Pectu, Bangs Laboratory, Zeng, or Murto, cure the deficiencies of Vemulapati (Remarks, p7-10).
Applicant’s arguments filed 03/13/2026 have been fully considered but are not found persuasive because the combined teachings of Vemulapati, Pennie, and MYC are not deficient as discussed above.
Applicant argues that the claims as amended are patentably distinct from the referenced co-pending applications or patents and requests withdrawal of the double-patenting rejections (Remarks, p10-12).
Applicant’s arguments filed 03/13/2026 have been fully considered but are not found persuasive. The claims are not distinct as discussed in detail above, and therefore, the double-patenting rejections have been maintained.
Conclusion
No claims are allowed.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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