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 .
Status of the Claims
Claims 1-11 and 24 are pending. Claims 1-11 and 24 are the subject of this NON-FINAL Office Action. This is the first action on the merits.
Election/Restrictions
Applicant’s election without traverse of the species (A) wherein the transposome complexes are immobilized to the surface of a degradable polyester bead, (B) the bead binding moiety is streptavidin or avidin and the polynucleotide binding moiety is biotin, and (C) the bead binding moiety is streptavidin or avidin and the polynucleotide binding moiety is biotin in the reply filed on 05/26/2026 is acknowledged. The claims directed to the unelected species have been canceled. The requirement is still deemed proper and is therefore made FINAL.
Claim Interpretation
Claim 1 recites a degradable polyester bead. This limitation will be interpreted as the polyester bead can be degraded by any means, so long as the melting point of the degradable polyester bead is from 50 ºC to 65 ºC. The specification indicates that any polyester bead, especially polycaprolactone, will meet this limitation. See Spec. paras. 0201-03 (“A “degradable polyester bead,” as used herein, can refer to any type of bead that comprises polyester and that can be degraded. In some embodiments, a degradable polyester bead may comprise a polymer. In some embodiments, polyester polymers are not cross-linked, allowing for relatively low polymer melting temperatures (such as, for example, approximately 60° C.). . . . ¶ For example, melting may convert polyester beads into smaller polycaprolactone (PCL) polymers or individual molecules of PCL. In some embodiments, a PCL bead can melt at temperatures above 50° C., such that the bead degrades into smaller PCL polymers or molecules of PCL. In some embodiments, a bead melts at temperature of 50° C. to 65° C. ¶ In some embodiments, beads may comprise polyesters other than PCL. In some embodiments, the polyester other than PCL has a melting temperature of 50° C. to 65° C. In other words, the degradable polyester bead may comprise any polyester with appropriate thermal properties. )
Claims 8 and 11 recite the limitation “wherein most transposome complexes are immobilized on the surface of the bead.”
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-8, 10-11 and 24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the polyester bead" in lines 7-8. There is insufficient antecedent basis for this limitation in the claim. The claim previously recites “a degradable polyester bead.” It is unclear whether “the polyester bead” refers to the degradable polyester bead, or whether it refers to another polyester bead.
Claims 3-8 refer to “the polyester bead” and do not refer to the degradable polyester bead.
Claim 3 recites the limitation "the bead" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the bead” refers to the degradable polyester bead, the polyester bead, or another bead.
Claim 7 recites the limitation "the bead" in lines 3 and 4-5. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the bead” refers to the degradable polyester bead, the polyester bead, or another bead.
Claim 8 recites the limitation "the bead" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the bead” refers to the degradable polyester bead, the polyester bead, or another bead.
Claim 10 recites the limitation "the bead" in lines 2 and 4. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the bead” refers to the polyester bead or whether it refers to another bead.
Claim 11 recites the limitation "the bead" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the bead” refers to the polyester bead or whether it refers to another bead.
Claim 24 recites the limitation "the bead" in line . There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the bead” refers to the polyester bead or whether it refers to another bead.
Claim 24 recites the limitation "the flow cell" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 24 depends upon claim 1, but claim 1 does not recite a flow cell. Claim 6 and claim 9 recite a flow cell, but claim 24 does not depend upon claim 6 or claim 9. It is unclear whether claim 24 is meant to refer to the degradable polyester bead of claim 1, whether claim 24 is meant to depend upon claim 6, whether claim 24 is meant to depend upon claim 9, or whether the flow cell is meant to refer to another claim or limitation.
Claims 2 and 4-6 are rejected by virtue of their dependency upon claim 1.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3-4, 6-11, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Steemers et al. (WO 2016/061517 A2; cited on the IDS filed 09/22/2025) in view of Khurana et al. (WO 2019/028047 A1; cited on the IDS filed 01/06/2023) and Gilligan (WO 2018/172726 A1) and evidenced by ThermoFisher Scientific (Avidin-Biotin Interaction. ThermoFisher Scientific. www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/avidin-biotin-interaction.html, 9 pages, available as of March 02, 2019).
Regarding claim 1, Steemers teaches a bead comprising a plurality of transposome complexes immobilized to the surface thereof, wherein each transposome complex comprises a transposase bound to a first polynucleotide and a second polynucleotide, wherein the first polynucleotide comprises a 3’ portion comprising a transposon end sequence and a tag, and the second polynucleotide comprises a 5’ portion that is complementary to and hybridized to the transposon end sequence (Fig. 2, Fig. 3, Fig. 12; pg. 17, lines 24-31; pg. 18, lines 1-15).
Steemers does not teach that the bead is a degradable polyester bead or that the polyester bead has a melting point of from 50 ºC to 60 ºC.
Khurana teaches a degradable hydrogel bead that can be selectively depolymerized (pg. 10, lines 36-37). Khurana teaches the degradation of the hydrogel beads allows for transport and seeding of sequencing libraries onto the surface of a flow cell (pg. 1, lines 35-36; pg. 2, lines 1-2).
Khurana teaches the hydrogel beads can comprise polycaprolactone (pg. 18, lines 30-36; pg. 19, lines 1-12; polycaprolactone named on line 6 of pg. 19).
Khurana teaches a solid surface that is appropriate for or can be modified to be appropriate for the attachment of materials for the processing of nucleic acids, including transposome complexes (pg. 40, lines 25-28).
Khurana teaches a separate tagmentation bead which is encapsulated into a hydrogel bead (pg. 23, lines 36-37; pg. 24, lines 1-4).
Gilligan teaches a bead comprising a transposase target sequence, a barcode sequence, and a primer sequence attached to the bead (pg. 3, lines 32-35; pg. 4, lines 1-2). Gilligan teaches the bead is a hydrogel bead, which is advantageous because they are compatible with efficient enzymatic reactions (pg. 4, lines 15-21).
It would have been obvious to one of ordinary skill in the art to substitute the bead taught by Steemers for a bead comprised of polycaprolactone as taught by Khurana in view of Gilligan. Gilligan teaches that transposome complexes can be attached to a hydrogel bead, and that these beads have the advantage of being compatible with efficient enzymatic reactions. Khurana teaches that hydrogel beads can be degradable and comprised of polycaprolactone, and teaches that the degradation of the hydrogel beads allows for transport and seeding of sequencing libraries onto the surface of a flow cell.
One of ordinary skill in the art would be motivated to use a degradable polyester such as polycaprolactone as taught by Khurana in the beads taught by Steemers, as Khurana teaches that degradable polyester beads have the advantage of allowing for transport and seeding of sequencing libraries on the surface of a flow cell. One of ordinary skill in the art would have a reasonable expectation of success as Gilligan teaches that transposome complexes can be attached onto a hydrogel bead and provides further motivation as the beads have the advantage of being compatible with efficient enzymatic reactions, with no evidence of unexpected results.
Regarding claims 3 and 4, Steemers teaches a biotin-streptavidin binding pair to immobilize the transposomes to the bead surface (pg. 15, lines 23-26) and teaches biotinylated transposons (pg. 16, lines 1-3).
Regarding claims 6 and 7, Khurana teaches the hydrogel beads can be captured on a flow cell (pg. 2, lines 24-33), such as through a receptor-ligand binding pair and gives the example of streptavidin and biotin (pg. 24, lines 25-32).
It would have been obvious to one of ordinary skill in the art to use the same type of binding moiety as the polynucleotide binding moiety and the flow cell binding moiety, and it would have been obvious to one of ordinary skill in the art to have the transposome complexes bound to a first portion of the bead binding moieties on the bead and have the flow cell binding moiety bound to a second portion of the bead binding moieties on the bead. As evidenced by ThermoFisher Scientific, streptavidin proteins can bind up to four biotin molecules (Introduction; Schematic of the Avidin-biotin interaction). As both Khurana and Steemers teach streptavidin-biotin binding pairs, and streptavidin can bind up to four biotin molecules, it would have been obvious to one of ordinary skill in the art to use streptavidin as the bead binding moiety and biotin as both the flow cell biding moiety and the polynucleotide binding moiety, with no evidence of unexpected results.
Regarding claim 8, Steemers teaches a target molecule bound to multiple transposome complexes on the bead (Fig. 14; pg. 18, lines 29-31; pg. 19, lines 1-3).
Regarding claim 9, Regarding claim 1, Steemers teaches a bead comprising a plurality of transposome complexes immobilized to the surface thereof, wherein each transposome complex comprises a transposase bound to a first polynucleotide and a second polynucleotide, wherein the first polynucleotide comprises a 3’ portion comprising a transposon end sequence and a tag, and the second polynucleotide comprises a 5’ portion that is complementary to and hybridized to the transposon end sequence (Fig. 2, Fig. 3, Fig. 12; pg. 17, lines 24-31; pg. 18, lines 1-15).
Steemers does not teach that the bead is a degradable polyester bead or that the polyester bead has a melting point of from 50 ºC to 60 ºC.
Khurana teaches a degradable hydrogel bead that can be selectively depolymerized (pg. 10, lines 36-37). Khurana teaches the degradation of the hydrogel beads allows for transport and seeding of sequencing libraries onto the surface of a flow cell (pg. 1, lines 35-36; pg. 2, lines 1-2). Khurana teaches the hydrogel beads can be captured on a flow cell (pg. 2, lines 24-33).
Khurana teaches the hydrogel beads can comprise polycaprolactone (pg. 18, lines 30-36; pg. 19, lines 1-12; polycaprolactone named on line 6 of pg. 19).
Khurana teaches a solid surface that is appropriate for or can be modified to be appropriate for the attachment of materials for the processing of nucleic acids, including transposome complexes (pg. 40, lines 25-28).
Khurana teaches a separate tagmentation bead which is encapsulated into a hydrogel bead (pg. 23, lines 36-37; pg. 24, lines 1-4).
Gilligan teaches a bead comprising a transposase target sequence, a barcode sequence, and a primer sequence attached to the bead (pg. 3, lines 32-35; pg. 4, lines 1-2). Gilligan teaches the bead is a hydrogel bead, which is advantageous because they are compatible with efficient enzymatic reactions (pg. 4, lines 15-21).
It would have been obvious to one of ordinary skill in the art to substitute the bead taught by Steemers for a bead comprised of polycaprolactone as taught by Khurana in view of Gilligan. Gilligan teaches that transposome complexes can be attached to a hydrogel bead, and that these beads have the advantage of being compatible with efficient enzymatic reactions. Khurana teaches that hydrogel beads can be degradable and comprised of polycaprolactone, and teaches that the degradation of the hydrogel beads allows for transport and seeding of sequencing libraries onto the surface of a flow cell.
One of ordinary skill in the art would be motivated to use a degradable polyester such as polycaprolactone as taught by Khurana in the beads taught by Steemers, as Khurana teaches that degradable polyester beads have the advantage of allowing for transport and seeding of sequencing libraries on the surface of a flow cell. One of ordinary skill in the art would have a reasonable expectation of success as Gilligan teaches that transposome complexes can be attached onto a hydrogel bead and provides further motivation as the beads have the advantage of being compatible with efficient enzymatic reactions, with no evidence of unexpected results.
Regarding claim 10, Steemers teaches a biotin-streptavidin binding pair to immobilize the transposomes to the bead surface (pg. 15, lines 23-26) and teaches biotinylated transposons (pg. 16, lines 1-3).
Regarding claim 11, Steemers teaches a target molecule bound to multiple transposome complexes on the bead (Fig. 14; pg. 18, lines 29-31; pg. 19, lines 1-3).
Regarding claim 24, Steemers teaches the bead can be from about 0.5 µm to about 5 µm, and teaches that the beads can be 1 µm or larger (pg. 38, lines 6-12). Khurana teaches the beads can be from about 2 µm to about 140 µm. It would have been obvious to one of ordinary skill in the art to use a diameter of 1 µm or larger as both Steemers and Khurana teach this diameter, and it would be a simple substitution of one size for another, with no evidence of unexpected results.
Claim(s) 2 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Steemers, Khurana, and Gilligan as applied to claim 1 above, and further in view of Fahmy et al. (WO 2016/161148 A1).
Steemers teaches a streptavidin magnetic bead (pg. 54, lines 19-20), but does not teach a plurality of magnetic nanoparticles immobilized on the bead. Steemers teaches that purification of the tagmentation reaction is readily achieved by immobilizing beads with a magnet (pg. 19, lines 17-20).
Fahmy teaches magnetic particles covalently linked to a hydrogel (pg. 3, lines 12-13; pg. 23, lines 13-17).
It would have been obvious to one of ordinary skill of the art to use magnetic nanoparticles covalently bound through a linker, as this is a known method in the art for including magnetic particles in a hydrogel and would be a simple substitution of one type of magnetic particle for another, with no evidence of unexpected results.
Prior Art
The following prior art teaches polyester or polycaprolactone beads with transposome complexes: WO 2019028166.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Randi L Beil whose telephone number is (571)272-1147. The examiner can normally be reached M-F 8:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/R.L.B./Examiner, Art Unit 1684 /AARON A PRIEST/Primary Examiner, Art Unit 1681
Prosecution Insights