Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Detailed Action
This office action is a response to applicant’s communication submitted May 22, 2026, wherein claims 2 and 11 are amended. This application is a continuation of US application 16/890752, now US patent 11254927, filed June 2, 2020, which is a continuation of US application 16/818458, now US patent 11060082, filed March 13, 2020, which is a continuation of US application 16/158752, now US patent 10590410, filed October 12, 2018, which is a continuation of US application 14/976746, now US patent 10100302, filed December 21, 2015, which is a continuation of US application 14/262525, now US patent 9217143, filed April 25, 2014, which is a continuation of US application 13/692980, now US patent 8710211, field December 3, 2012, which is a continuation of US application 12/172214, now US patent 8324372, filed July 11, 2008, which claims benefit of provisional application 60/959437, filed July 13, 2007.
Claims 2, 4-11, 13-15, and 17-21 are pending in this application.
Claims 2, 4-11, 13-15, and 17-21 as amended are examined on the merits herein.
The following rejections of record in the previous action are maintained:
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 2, 4-11, 14-15 and 17-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 2 is directed to a kit which is composed of a process tube containing beads which are amide-bonded to polycationic polyamine dendrimers, and a lytic enzyme, and further composed of a release solution capable of eluting nucleic acids from the beads, a pipette tip configured to dispense the release solution into the process tube, and a separate microfluidic cartridge configured to receive polynucleotides released form the beads. The beads are further described as carboxyl-modified beads to which polyamine dendrimers are linked via one or more carbodiimide bonds. As discussed under 35 USC 112(a), the limitation requiring the dendrimer to be linked via one or more carbodiimide bonds is new matter not supported by the original disclosure, and appears to be intended to refer to amide bonds produced using carbodiimide coupling agents. Therefore this limitation is interpreted as requiring that somewhere within the structure of the dendrimer-bead conjugate there be an amide bond attaching a dendrimer portion to the bead. While claim 2 has been amended to describe an intended use wherein the magnetic beads are suspended in the solution, this limitation is reasonably considered to merely require that the magnetic beads are in a form that could be suspended in a solution, whether or not they are specifically suspended in a solution in actual practice.
Dependent claims 4-7 and 10 further specify structural limitations of the dendrimers. Dependent claims 8 and 9 further define the contents of the container. Claims 11, 13-15 and 17--21 are directed to a kit essentially comprising the same elements.
Farchaus et al. discloses a biological sample preparation system comprising a dried reagent on top of a separation column. (p. 4 lines 10-15) In a particular embodiment the dried reagent is intended to process a biological sample when reconstituted in aqueous solution and the separation column is intended to separate components of interest form the biological sample. (p. 4 line 16-23) In one embodiment the reagent system is intended to isolate label, detect, amplify, modify, or sequence nucleic acids. (p. 9 lines 8-15) In a particular embodiment the dried reagent is a lysis reagent such as proteinase K. (p. 5 lines 2-3) Various different separation devices can be used in these sample preparation systems, including a column containing a matrix. (p. 5 lines 6-11, p. 10 lines 17-24) These columns are used in methods of preparing a biological sample by adding an aqueous solution and a biological sample to the dried reagent solution, incubating the combination to process the sample, and separating the components of the sample. (p. 6 lines 13-22) Therefore these columns are reasonably considered to fall within the scope of “process tubes” recited in present claims 2 and 11.
Regarding the presence of a release solution and a pipette tip in the kit, Farchaus et al. describes the use of pipette tips and elution steps in their working examples. (p. 17 line 15 – p. 18 line 12) It would therefore have been obvious to one of ordinary skill in the art to package the columns described by Farchaus et al. along with appropriate reagents such as an elution buffer and other elements such as pipette tips, as doing so is directly suggested by the fact that Farchaus et al. describes these elements as being necessary to use the disclosed columns.
Regarding the limitation requiring that the kit contain an additional microfluidic cartridge external to the container that is configured to receive polynucleotides released from the beads, Farchaus et al. does not specifically disclose a kit having an additional microfluidic cartridge as described in this limitation. However, Farchaus et al. does disclose that the purified nucleic acids released from the device can be used for analytical techniques such as amplification, as discussed above. Tyvoll et al. further discloses a microfluidic device for enriching and amplifying a particular nucleic acid target sequence form a sample. (p. 1 paragraph 4, also figures 10-12, for example) This device is reasonably considered to fall within the scope of a cartridge as recited in present claims 2 and 11. This device enriches the nucleic acid by specifically binding the target nucleic acid preferentially from other nucleic acids. (p. 3 paragraphs 39-43) This is a different method of purification and solves a different problem than the removal of non-nucleic-acid inhibitory compounds described in the disclosure of Farchaus et al. The assay performed by the device can include polymerase chain reaction. (p. 8 paragraph 83)
It would therefore have been obvious to one of ordinary skill in the art to include in a kit for nucleic acid analysis both one or more spin columns according to Farchaus et al. and one or more cartridges according to Tyvoll et al. One of ordinary skill in the art would have considered these two cartridges to be useful together for the purpose of analyzing a biological sample, first by purifying nucleic acids from a biological sample and then by selecting and amplifying a particular target nucleic acid to be analyzed.
Farchaus et al. additionally does not disclose a kit or system wherein the matrix for purifying the nucleic acid is a dendrimer attached to magnetic particles as recited in the present claims.
Yoza et al. discloses a DNA extraction method based on dendrimer-modified magnetic particles bearing a polyamidoamine (PAMAM) dendrimer. (p. 21 left column third paragraph) These dendrimers are based on 3-[2-(2-aminoethyl)ethylamino]propyltrimethoxysilane (AEEA) further reacted with sequential cycles of methyl acrylate and ethylenediamine. (p. 21 right column, “modification of bacterial and artificial magnetic particles with a hyperbranched polyamidoamine dendrimer”) These dendrimers were constructed from between 1-6 generations. (p. 23 table 1) These particles were found to bind and release DNA. (p. 24 right column third paragraph, also table 3)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use a cationic PAMAM dendrimer as described by Yoza et al. as the matrix in the system described by Farchaus et al., and to assemble a kit or system containing lyophilized dendrimer modified particles, a lytic enzyme, and release solution as described in the present claims. One of ordinary skill in the art would have seen the disclosure of Farchaus et al. as generally describing a matrix for binding DNA as being useful in such a system, and therefore would have realized that the dendrimers described by Yoza et al. are useful for this purpose.
With respect to the particular structural elements described in claims 4-7, 10, 12-15, 17, and 21, the dendrimers described by Yoza et al. would have the following structure:
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With the exact molecular weight, and number of branches and amino groups, depending on the generation to which it is constructed. Because Yoza et al. discloses that the generation can be anywhere between 1 and 6, one of ordinary skill in the art would have found it to be obvious to use any of these different generations of dendrimers as the matrix in the methods of Farchaus et al., rendering obvious larger dendrimers having the number of amine groups recited in claims 4, 6, and 7, or smaller dendrimers having a low molecular weight as recited in claim 5, for example.
With respect to the requirement that the dendrimer is connected via amide bonds as recited in present claims 2 and 16, the claims do not describe a specific structural formula localizing the amide bond to a particular position. Therefore the broadest reasonable interpretation of “amide bonded” as it is used in the claims merely requires that somewhere in the dendrimer structure there exists an amide bond with a dendron structure on one side and a linker structure connecting to the particle on the other side. Since the PAMAM dendrimers described by Yoza et al. contain amide bonds fulfilling these criteria, they infringe this limitation. Similarly, with respect to the “initial monomer core of ethylene diamine,” as recited in present claims 10 and 21, the present claims are not directed to a synthetic process where there is a clearly defined initial starting material, nor are they directed to a specific chemical structure having an ethylenediamine moiety in a particular position. Rather, the broadest reasonable interpretation of this limitation is merely that there exists an ethylenediamine substructure somewhere within the larger structure of the dendrimer. Because this is clearly the case for the PAMAM dendrimer described by Yoza et al., these claims are infringed by this structure as well. Further regarding the reference to a carbodiimide in present claim 2, as discussed under 35 USC 112(a), for the sake of this action this limitation is interpreted as a product-by-process limitation requiring that the amide bond be one which could have been formed using a carbodiimde coupling agent. Looking to the PAMAM structure above, the amide bonds in said structure could in fact have been formed using a carbodiimide coupling agent.
For these reasons the invention taken as a whole is prima facie obvious.
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 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11254927. (of record in previous action, herein referred to as ‘927) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action)
Specifically, claims 1 and 15 of ‘927 claim a system or kit comprising dendrimer-coated magnetic beads, a lytic enzyme, and a release solution as recited in present claims 2 and 11. With respect to the newly added limitation requiring that the kit also contain a microfluidic cartridge external to the container configured to receive polynucleotides released from the beads, claim 1 of ‘927 further describes the kit as including a microfluidic cartridge configured to receive polynucleotides from the polynucleotide-retained beads. Since this cartridge is separate from the beads, it would necessarily be external to whatever the chamber contained the beads, meeting this limitation. Dependent claims 2-8, 14, 16-19, and 22 further define the structure of the dendrimers in the same manner as present claims 2-7, 10-18, and 21. Dependent claims 9-13 and 20-21 define additional features of the kit as recited in present claims 8, 9, 19, and 20. While the claims of ‘927 do not specifically describe the container as a process tube, as discussed under 35 USC 103(a), Farchaus et al. describes a device which is a spin column reasonably considered to fall within the scope of “process tube” which further contains a matrix and a lytic enzyme, and is configured to receive a biological sample and separate nucleic acids from the sample. Therefore in view of this disclosure one of ordinary skill in the art would have found it to be obvious that the “container” containing the lytic reagent and the magnetic beads described in the claims of ‘927 could be arranged as a centrifuge tube, as described by Farchaus. Furthermore as described under 35 USC 103(a) Farchaus et al. suggests methods of using these devices that involve pipette tips, rendering obvious the inclusion of a pipette tip in the kit.
Claims 2, 4-11, 11-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-7 of U.S. Patent No. 10494663 (of record in previous action, herein referred to as ‘663) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022)
Independent claim 1 of ‘663 is directed to a method comprising lysing a biological sample with a lysing reagent, retaining a polynucleotide from the biological sample on binding particles comprising a polycationic molecule, and later releasing the polynucleotides using a release solution, and receiving the released polynucleotides into a second region for processing the sample, which could reasonably be considered to be an additional cartridge as required by the newly introduced limitations in claims 2 and 11. Dependent claims 4-5 of ‘663 further specify that the polycationic substance is connected to the binding particles by carboxylic groups. Claims 6 and 7 of ‘663 further recite that the binding particles are preloaded with a lysing reagent that can be proteinase K. While the claims of ‘663 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, and Farchaus et al. discloses a system comprising dried lytic reagent and a nucleic acid binding matrix that meets all of the other claim limitations. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘663 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides. Furthermore as described under 35 USC 103(a) Farchaus et al. suggests methods of using these devices that involve pipette tips, rendering obvious the inclusion of a pipette tip in the kit.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11060082 (of record in previous action, herein referred to as ‘062) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘082 is directed to a composition of carboxyl-modified magnetic beads bound via amide bonds to polycationic polyamine dendrimers. Dependent claims 2-18 of ‘082 further specify that the dendrimer is a PAMAM dendrimer having a structure falling within the limitations recited in present claims 2-7, 10-18, and 21. While the claims of ‘082 do not specifically claim the beads as part of a DNA-binding kit or system having the additional components recited in present claims 2 and 11, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system comprising dried lytic reagent and a nucleic acid binding matrix that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification columns. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use the PAMAM coated beads claimed by ‘082 in such a system, as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-13, 14, 16, 19, and 20 of U.S. Patent No. 10590410 (of record in previous action, herein referred to as ‘410) in view of Farchaus et al. (PCT international publication WO2008/118566, of record in previous action) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 8 of ‘410 is directed to a method of nucleic acid isolation comprising contacting a biological sample with binding particles amide-bonded to a polycationic dendrimer. Dependent claims 9-12 further define the dendrimer as a PAMAM having the same structure recited in present claims 2-7, 10-18, and 21. Claim 14 of ‘410 describes the binding particles as magnetic. Claim 16 of ’410 further describes using a lysis solution to lyse the biological sample.
While the claims of ‘410 do not specifically claim the beads as part of a DNA-binding kit or system having the additional components recited in present claims 2 and 11, as discussed previously under 35 USC 103, Farchaus et al. discloses a system comprising dried lytic reagent and a nucleic acid binding matrix that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use the PAMAM coated beads claimed by ‘410 in such a system, as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA as required by the systems disclosed by Farchaus et al. and Tyvoll et al.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10100302 (Cited in PTO-1449 submitted 4/11/2022, herein referred to as ‘302) in view of Farchaus et al. (PCT international publication WO2008/118566, of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘082 is directed to a kit comprising a lysis buffer, binding particles having PAMAM generation zero covalently bound, a wash solution, and a release solution. Dependent claims 2, 3, 5-6, and 14 of ‘302 further specify that the PAMAM dendrimer has a structure falling within the limitations recited in present claims 2-7, 10-18, and 21. While the claims of ‘302 do not specifically claim the lysis buffer, binding particles, and release solution as parts of a system or kit having a container recited in present claims 2 and 11, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system comprising dried lytic reagent and a nucleic acid binding matrix that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use the PAMAM coated beads and other components claimed by ‘302 in such a system, as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, and 7 of U.S. Patent No. 8710211 (of record in previous action, herein referred to as ‘211) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘211 is directed to a method of nucleic acid isolation comprising contacting a biological sample with a lysis solution, and then with magnetic binding particles amide-bonded to a polycationic PAMAM dendrimer, before further washing the particles and then contacting them with a release solution. Dependent claim 2 further defines the dendrimer as a PAMAM generation zero dendrimer which according to the figure on p. 19 of the specification as originally filed has a structure falling within the dendrimer structure recited in present claims 2-7, 10-18, and 21.
While the claims of ‘211 do not specifically claim the beads as part of a DNA-binding kit or system configured as recited in present claims 2 and 11, as discussed previously under 35 USC 103, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use the PAMAM generation zero coated beads and other reagents claimed by ‘211 in such a system, as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA as required by the system disclosed by Farchaus et al.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 6, and 9 of U.S. Patent No. 8324372 (of record in previous action, herein referred to as ‘372) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘372 is directed to a method of nucleic acid isolation comprising contacting a biological sample with a lysis solution, and then with magnetic binding particles amide-bonded to a polycationic PAMAM generation zero dendrimer, before further washing the particles and then contacting them with a release solution. According to the figure on p. 19 of the specification as originally filed, the PAMAM generation zero dendrimer has a structure falling within the dendrimer structure recited in present claims 2-7, 10-18, and 21. Claims 5 and 6 of ‘372 further specify that the dendrimer is covalently linked to carboxyl groups of the polymeric material, and claim 9 specifies that at least some of the particles are magnetic.
While the claims of ‘372 do not specifically claim the beads as part of a DNA-binding kit or system configured as recited in present claims 2 and 11, as discussed previously under 35 USC 103, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use the PAMAM generation zero coated beads and other reagents claimed by ‘372 in such a system, as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA as required by the system disclosed by Farchaus et al.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 15-25 of U.S. Patent No. 9217143 (of record in previous action, herein referred to as ‘143) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘143 is directed to a method of nucleic acid isolation comprising contacting a biological sample with a lysis solution, and then with magnetic binding particles amide-bonded to a polycationic PAMAM generation zero dendrimer, before further washing the particles and then contacting them with a release solution. According to the figure on p. 19 of the specification as originally filed, the PAMAM generation zero dendrimer has a structure falling within the dendrimer structure recited in present claims 2-7, 10-18, and 21. Claims 15-25 of ‘143 further specify particular structural features of the dendrimer recited in the present claims.
While the claims of ‘143 do not specifically claim the beads as part of a DNA-binding kit or system configured as recited in present claims 2 and 11, as discussed previously under 35 USC 103, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use the PAMAM generation zero coated beads and other reagents claimed by ‘143 in such a system, as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA as required by the system disclosed by Farchaus et al.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 10364456 (of record in previous action, herein referred to as ‘456) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘456 is directed to a method comprising retaining a polynucleotide on binding particles comprising a polycationic substance, and then releasing the polynucleotides using a release solution. Dependent claim 4 of ‘456 further specifies that the polycationic substance is connected to the binding particles by carboxylic groups. While the claims of ‘456 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification cartridge. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘456 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 10443088 (of record in previous action, herein referred to as ‘088) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘088 is directed to a method comprising retaining a polynucleotide on binding particles comprising a polycationic substance, and then releasing the polynucleotides using a release solution. Dependent claim 4 of ‘088 further specifies that the polycationic substance is connected to the binding particles by carboxylic groups. While the claims of ‘088 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘088 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 9382532 (of record in previous action, herein referred to as ‘532) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘532 is directed to a method comprising binding a polynucleotide from a biological sample to binding particles comprising a polycationic dendrimer molecule, and later releasing the polynucleotides using a release solution. Dependent claim 2 of ‘532 specifies that the microparticles are magnetic microparticles, and that they are bonded to the cationic dendrimer by an amine-reactive ester. While the claims of ‘532 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘532 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 9540636 (of record in previous action, herein referred to as ‘636) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘636 is directed to a method comprising binding a polynucleotide from a biological sample to binding particles comprising a polycationic dendrimer molecule, and later releasing the polynucleotides using a release solution. Dependent claim 2 of ‘636 specifies that the microparticles are magnetic microparticles, and that they are bonded to the cationic dendrimer by an amine-reactive ester. While the claims of ‘636 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘532 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 8852862 (of record in previous action, herein referred to as ‘862) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘862 is directed to a method comprising retaining a polynucleotide on binding particles comprising a polycationic substance, and then releasing the polynucleotides using a release solution. While the claims of ‘862 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘862 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 6 of U.S. Patent No. 10604788 (of record in previous action, herein referred to as ‘788) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘788 is directed to a system for isolating polynucleotides form a biological sample comprising a lysing container comprising magnetic binding particles comprising a polycationic substance, and a release solution. Dependent claim 5 and 6 of ‘788 further specify that proteinase K is included in the lysing chamber as a lysing reagent. While the claims of ‘788 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘788 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides.
Claims 2, 4-11, 13-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21, 25, and 28 of U.S. Patent No. 8570586 (of record in previous action, herein referred to as ‘586) in view of Farchaus et al. (PCT international publication WO2008/118566, Reference of record in previous action) in view of Yoza et al. (“Fully Automated DNA extraction from Blood Using Magnetic Particles Modified with a Hyperbranched Polyamidoamine Dendrimer,” Journal of Bioscience and Bioengineering vol. 95 no. 1 pp. 21-26, Reference 1691 cited in PTO-1449 submitted April 11, 2022) in view of Tyvoll et al (US pre-grant publication 2004/0086870, cited in PTO-1449 submitted April 30, 2024)
Independent claim 1 of ‘586 is directed to a device for isolating polynucleotides form a biological sample comprising a lysing container comprising magnetic binding particles comprising a polycationic substance. Dependent claim 21 of ‘788 further specify that a lysing reagent is included in the lysing chamber. Dependent claim 25 specifies that the polycationic substance is attached to a carboxyl group of the particles by an amide bond. Claim 28 of ‘586 recites that at least some of the particles are magnetic. While the claims of ‘586 do not claim a DNA-binding kit or system having the additional components recited in present claims 2 and 11, comprising a PAMAM dendrimer, as discussed previously under 35 USC 103, Yoza et al. discloses that PAMAM dendrimer coated beads can bind DNA, Farchaus et al. discloses a system using a DNA binding column that meets all of the other claim limitations, and Tyvoll et al. discloses a different cartridge for selectively amplifying a target nucleic acid from a mixture that one of ordinary skill in the art would have recognized as useful for further processing nucleic acids released from Farchaus’s purification column. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use polycationic coated beads claimed by ‘586 in a polynucleotide purification system as described by Farchaus et al., as one of ordinary skill in the art would have expected that they were useful for binding and purifying DNA. It would also have been obvious to one of ordinary skill in the art to use one of the PAMAM dendrimers described by Yoza as the polycationic binding moiety, in view of the fact that Yoza et al. describes these moieties as being useful for the same purpose of binding polynucleotides.
Response to Arguments
Applicant’s arguments, submitted May 22, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that the cited prior art does not each or suggest embodiments wherein the beads are carboxyl-modified, in particular wherein the amide bond is between a surface carboxyl group on the magnetic beads and a primary amine of the polycationic polyamine dendrimer.
Firstly, the examiner notes that present claims 2 and 11 are directed to a kit rather than a process. Any process steps described relating to forming an amide bond are product-by-process limitations and would be infringed by any bead containing an amide bond that could have been formed according to the presently recited steps. More specifically, in order to infringe the claims, a dendrimer coated bead must contain an amide bond wherein the carbonyl portion of the amide is a surface carboxyl group of the carboxyl modified magnetic beads. A review of the specification does not indicate that this term has been particularly defined in such a way as to require that the carboxyl group be attached to the rest of the bead in such a way that it is exposed on the surface of the bead. The claims still do not specify what particular attachment connects the carboxyl to the rest of the bead.
This is important because, as discussed in the previous office action, the conjugates actually used in the method of Yoza are seen to have a structure of:
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This structure could reasonably be derived by an amidation reaction connecting the following carboxyl-coated bead:
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to an amine-containing dendrimer in order to produce the full structure. This carboxyl-containing structure can reasonably be considered to be a surface carboxyl of a carboxyl coated magnetic bead. While Yoza describes the beads as being modified with AEEA, an amine modification agent, and then subjected to construction of a dendrimer, this is not the only way to conceptualize the construction of such a structure. For example Peter (US pre-grant publication 2010/0062474, cited in PTO-892, cited as an evidentiary reference to illustrate the scope of the claims) describes functionalized magnetic beads capable of binding substance from culture medium. (p. 2 paragraph 14) The construction of these beads is described as proceeding by reacting an amino functionalized bead with methyl acrylate in order to functionalize the surface of the bead with carboxyl groups, which can be further reacted with amines to form dendrimers on the surface of the beads. (p. 3 paragraph 26, p. 3 paragraph 39 – p. 4 paragraph 49) Because the claims are directed to a kit and the beads are described by a product-by-process limitation, rather than actually claiming a method of making said beads or a specific chemical structure that would exclude Yoza’s beads, the claims are seen to be infringed by these beads regardless of the specifics of how Yoza describes them being produced. Furthermore because the structure would include ethylenediamine as the first compound reacted with the carboxyl, this would reasonably be considered to fall within the broadest reasonable interpretation of “a plurality of terminal primary amines around a diamine core.”
Applicant further argues that because present claims 2 and 11 refer to a covalent bond between a terminal group of the dendrimer and the carboxyl group of the bead, this differentiated the claimed structure from the prior art, because the structure produced by Yoza’s method involves building the dendrimers directly on the surface of the beads rather than attaching already-formed dendrimers to the surface of a bead. Applicant’s argument rests on the interpretation of “terminal primary amine” as not including the amine involved in the innermost amide bond. By way of illustration, the beads described by Yoza would involve an amide bond between the amine-containing dendrimer:
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and the carboxylated bead:
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. In its broadest reasonable interpretation, in the absence of a specific chemical structure, both the rightmost (blue) and leftmost (green) primary amines are “terminal” because they occur at the end of a chain and any tertiary amines within the structure are not terminal. If one of ordinary skill in the art were to give this term its broadest reasonable interpretation, then any such dendrimer according to Yoza, regardless of its generation, would have a single “right-hand” terminal amine that participates in the amide bond connecting the dendrimer to the particle.
For these reasons the rejections are deemed proper and maintained.
In addition, Applicant’s attention is directed to the non-patent reference Si et al. (Reference included with PTO-892) Even assuming for the sake of argument that some or all of the arguments discussed above were valid so as to differentiate the beads recited in the present claims from those described by Yoza, such an amendment would simply necessitate a new ground of rejection over the cited references and further in view of this reference. Si et al. describes an alternate form of dendrimer-coated magnetic bead wherein an acrylamide bearing magnetic bead is treated with an activating agent and then reacted with a terminal amine of a fully formed PAMAM dendrimer. (see abstract, also p. 384 sections 1.1-1.5) While the dendrimer is reacted with a glutaraldehyde-activated amide rather than a free carboxylate, the resulting amide would be identical to an amide formed in any other manner such as direct reaction of a carboxyl with a primary amine. Therefore in such a case it would still have been obvious to one of ordinary skill in the art to use dendrimer-coated magnetic beads produced by Si’s method in place of dendrimer-coated magnetic beads coated by Yoza’s method. One of ordinary skill in the art would have seen these two beads as equivalents usable for the same purpose.
Conclusion
No claims are allowed in this action. THIS ACTION IS MADE FINAL. 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.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 7/15/2026
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