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 .
REQUEST FOR CONTINUED EXAMINATION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/02/2026 has been entered.
Information Disclosure Statement
An IDS has not been filed in the instant application.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application 62/756419 filed 11/06/2018 is acknowledged.
Status of Claims
Amendments to the claims are acknowledged. Claims 7 and 34 are cancelled.
Claims 1-6, 23-33 and 35-38 are under examination.
Claims 8-22 are withdrawn.
Claim Rejections - 35 USC § 112-2nd paragraph
The rejection of claim 35 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ),
second paragraph, is in part withdrawn in view of Applicant’s amendments filed 6/2/2026. The following over claims 38 maintained and further necessitated in view of Applicant’s amendments.
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 1-6, 23-33 and 35-38 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 pre-AIA the applicant regards as the invention.
Claims 1, 23 and 35 have been amended to recite “wherein the process is a nondestructive process.” There is lack of antecedent basis support for this limitation. It is unclear what steps specifically are being referred to as “the process” which is nondestructive. Furthermore, “nondestructive” is a relative term and it is unclear what the metes and bound of “nondestructive” are. Term is not defined in the specification and the claim does not set forth what is not being destroyed . It is unclear what destruction is avoided (or what is being preserved) and what the specific steps were implemented to achieve that nondestructive effect. The limitation is therefore indefinite because it is unclear what “the process is a nondestructive process” is referring to.
Claim 38 recites “the oligonucleotide” and “the binding protein.” There is insufficient antecedent basis for these limitations. The claims from which this claim depends recite “polynucleotide” and “the binding molecule.” The claims do not provide antecedent basis for an oligonucleotide or binding protein.
Response to Arguments
Applicant's arguments filed 6/2/2026 have been fully considered but they are not persuasive.
Applicants have clarified some of the deficiencies set forth under 112(b) in the previous Office Action of 3/2/2026, except for the recitation of “the binding protein” and “the oligonucleotide” in claim 38. If applicants intended that the binding protein is the protein needed for gRNA to bind, Applicants should clarify the claim language to provide antecedent basis for “the binding protein.” It is suggested the claim recite “wherein the guide RNA binds to a specific binding protein” before reciting “the binding protein.” Regarding “the oligonucleotide,” independent claim 35 recites “an oligonucleotide primer” and refers to this as “the primer.” Therefore it remains unclear if “the oligonucleotide” in claim 38 is referring to “the primer” oligonucleotide of claim 35 or something else. Clarification of antecedent basis is needed.
Furthermore, Applicants have introduced new issues of indefiniteness in claims 1, 23, and 35, as set forth above.
Claim Rejections - 35 USC § 103
Claims 7 and 34 have been cancelled and therefore withdrawn from the rejection.
The following rejection is maintained from the previous Office Action of 3/2/2026 and modified in view of amendments filed 6/2/2026.
The following is a quotation of 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 of this title, 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 negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-6 and 35-36 are rejected under 35 U.S.C. 103(a) as being unpatentable over Loehrlein et al. (US 2002/0160361) in view of Rutten (Nature Reviews Chemistry vol 2 (Published: 30 October 2018) 365-381).
Loehrlein et al. teach methods of gene expression analysis wherein information is stored on DNA (Abstract)(i.e. a database of data filed which are DNA’s).
Loehrlein et al. teach (par. 0162) contacting labeled DNA with beads bearing avidin or antibody, wherein the labeled DNA is labeled with biotin and antigen that binds of the avidin or antibody on the bead; Loehrlein teach (par. 0050) that a detectable moiety is synonymous with a label used to distinguish a particular nucleic acid (i.e. the DNA is labeled with a chemical moiety); Loehrlein et al. teach that the beads may be magnetic beads (par. 0162) (i.e. contacting the database with a magnetic bead comprising a corresponding chemical group that binds to the moiety), as in claims 1 and 35.
Loehrlein et al. teach a magnetic platform to precipitate the DNA bound to the beads (par. 0252) wherein the magnetic separation is performed with a moiety (par. 0044)(i.e. extracting the one or more polynucleotide strands bearing the data file using a magnet), as in claims 1 and 35.
Loehrlein et al. does not specifically teach providing an oligonucleotide primer that selectively binds a polynucleotide strand bearing a datafile, wherein the primer is labeled with a chemical moiety.
Loehrlein et al. does not specifically teach wherein the datafile is repeatedly extracted from the database, wherein the process is a nondestructive process and wherein the datafile comprises a subset of encoded information corresponding to a portion of the plurality of polynucleotide strands of the database.
Rutten et al. however teach encoding information into polymers and using DNA as an alternative for data storage (Abstract). Rutten et al. teach data storage in DNA where DNA strands that encode the data have attached forward and reverse primers (page 5, Figure 1)(i.e. providing an oligonucleotide primer that selectively binds a polynucleotide strand bearing a datafile), as in claims 1 and 35.
Rutten et al. teach a forward primer and a primer “key” (Figure 1)(i.e. chemical moiety or which also reads on a “physical occlusion”), as in claims 1 and 35.
Rutten et al. teach (page 366, col. 1, par. 1) that “We are interested in technology that can reliably store a sequence of bits in a polymer and, at some later point, reliably extract exactly the same sequence from the polymer again.” Rutten et al. teach (page 366, col. 1, par. 3) “reading sequences at the single molecule level, are currently under active exploration. These new methods, also referred to as third generation sequencing, allow longer reads and higher sequencing speeds and make use of smaller and often portable equipment. In particular, nanopore sequencing, which monitors modulations in ion current that occur when a DNA molecule translocates a narrow (protein) channel and translates them into the primary sequence of the strand, is a revolutionary advance that has been commercialized recently.” Rutten teach data storage in DNA by applying commercial synthesis protocols and standard sequencing techniques (par. 369, col. 2, par. 3) which is not a destructive process.
Rutten et al. also teach (page 370, col. 2, par. 2) “DNA can be stored on a solid support, in which one end of the double-stranded DNA is immobilized, reducing the risk of unwanted strand aggregation. Storage in solution is also possible, however. The latter enables more rapid replication and sequencing, as the molecules are more flexible and more easily accessible.” Rutten teaches rewriting of stored DNA (page 370, col. 1, par. 1) by addressing random access and rewritability; DNA is accessed, read and if needed rewritten by introducing overhangs (page 370, col. 2, par. 2). Rutten therefore suggest that the DNA is not destroyed, can be accessed repeatedly from its storage (i.e. database). Rutten et al. teach that DNA can be modified, amplified and is stable (page 371, col. 1, par. 2) In these processes taught by Rutten, the DNA may be accessed without destroying the DNA. Sequencing DNA at a single molecule level or in solution by PCR amplification does not destroy the DNA.
Rutten et al. teach, “To prevent this data corruption problem, multiple copies of the DNA strand are often used,” (page 366, col. 2, par. 3)(i.e. wherein the datafile comprises a subset of encoded information corresponding to a portion of the plurality of polynucleotide strands in the database).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have applied the method of attaching magnetic beads and moieties to separate DNA as taught by Loehrlein et al. to the method of storing information in DNA as taught by Rutten et al. Loehrlein et al. teach attaching primers to target sequences (par. 0005) wherein the primers may be forward and reverse primers (par. 0006) and that the primers may be coupled with a moiety (par. 0168). Rutten et al. teach forward and reverse primers and a “key” primer attached to the information carrying DNA sequence (i.e. data file). At the time of invention, a practitioner could have added a moiety with a magnetic bead as taught by Loehrlein et al. to the DNA data file as taught by Rutten et al. The predictable result of datafile DNAs with magnetic bead labeled moieties would be achieved. Such a combination is merely a "predictable use of prior art elements according to their established functions." One of ordinary skill could have also substituted the concept of having a primer “key” of Rutten et al. with a magnetic bead carrying moiety as taught by Loehrlein et al. Such would be a simple substitution of one known element for another to obtain predictable results. KSR Int’l 7, 127 S. Ct. at 1740.
Regarding dependent claims 2-6
Loehrlein et al. teach DNA (par. 0005), as in claim 2.
Loehrlein et al. teach biotin and antibody moieties (par. 0162) and streptavidin (par. 0179) and streptavidin coated magnetic beads (par. 0252), as in claim 3..
Loehrlein et al. teach amplification (par. 0004-0005), as in claim 4.
Loehrlein et al. teach sequencing (par. 0003 and 0076), as in claim 5.
Rutten et al. sequencing and error correction (page 5, section “Error correction”) (i.e. performing error analysis of sequencing data), as in claims 6.
Both Loehrlein et al. and Rutten et al. generally teach a system for use in carrying out a process as set forth in claim 35.
Loehrlein et al. teach double stranded polynucleotides (par. 0049), as in claim 36.
Claims 23-33 and 37-38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Loehrlein et al. (US 2002/0160361) in view of Rutten (Nature Reviews Chemistry vol 2 (2018) 365-381) and further in view of Dekker et al. (Nucleic Acid Research vol. 32 (2004) pages 1-8).
Loehrlein et al. teach methods of gene expression analysis wherein information is stored on DNA (Abstract)(i.e. a database of data filed which are DNA’s).
Loehrlein et al. teach (par. 0162) contacting labeled DNA with beads bearing avidin or antibody, wherein the labeled DNA is labeled with biotin and antigen that binds of the avidin or antibody on the bead; Loehrlein teach (par. 0050) that a detectable moiety is synonymous with a label used to distinguish a particular nucleic acid (i.e. the DNA is labeled with a chemical moiety); Loehrlein et al. teach that the beads may be magnetic beads (par. 0162) (i.e. contacting the database with a reagent that selectively binds a location on one or more polynucleotide strands not occluded by the physical occlusion), as in claim 23 and 25.
Loehrlein et al. teach a magnetic platform to precipitate the DNA bound to the beads (par. 0252) wherein the magnetic separation is performed with a moiety (par. 0044)(i.e. extracting the one or more polynucleotide strands bearing the data file using the reagent), as in claim 23 and 25.
Loehrlein et al. teach a “blocking group” (par. 0039) which reads on a physical occlusion but do not specifically teach that the physical occlusion comprises a single strand polynucleotide overhang (ss overhang) on the one or more double stranded polynucleotide strands bearing the datafile or wherein the physical occlusion comprises a DNA binding molecule, as in claim 23.
Loehrlein et al. does not specifically teach providing a database of a plurality of polynucleotide strands wherein the datafile comprises information encoded into double stranded (ds) polynucleotide strands, as in claim 23 .
Rutten et al. however teach encoding information into polymers and using DNA as an alternative for data storage (Abstract and pages 2-4). Rutten et al. teach data storage in DNA where DNA strands that encode the data have attached forward and reverse primers (page 5, Figure 1)(i.e. providing a database of a plurality of polynucleotide strands wherein the datafile comprises information encoded into double stranded (ds) polynucleotide strands), as in claims 23 and 25.
Rutten et al. teach a forward primer and a primer “key” (Figure 1)(i.e. chemical moiety or which also reads on a “physical occlusion”), as in claim 23 and 25.
Rutten et al. teach (page 366, col. 1, par. 1) that “We are interested in technology that can reliably store a sequence of bits in a polymer and, at some later point, reliably extract exactly the same sequence from the polymer again.” Rutten et al. teach (page 366, col. 1, par. 3) “reading sequences at the single molecule level, are currently under active exploration. These new methods, also referred to as third generation sequencing, allow longer reads and higher sequencing speeds and make use of smaller and often portable equipment. In particular, nanopore sequencing, which monitors modulations in ion current that occur when a DNA molecule translocates a narrow (protein) channel and translates them into the primary sequence of the strand, is a revolutionary advance that has been commercialized recently.” Rutten teach data storage in DNA by applying commercial synthesis protocols and standard sequencing techniques (par. 369, col. 2, par. 3) which is not a destructive process.
Rutten et al. also teach (page 370, col. 2, par. 2) “DNA can be stored on a solid support, in which one end of the double-stranded DNA is immobilized, reducing the risk of unwanted strand aggregation. Storage in solution is also possible, however. The latter enables more rapid replication and sequencing, as the molecules are more flexible and more easily accessible.” Rutten teaches rewriting of stored DNA (page 370, col. 1, par. 1) by addressing random access and rewritability; DNA is accessed, read and if needed rewritten by introducing overhangs (page 370, col. 2, par. 2). Rutten therefore suggest that the DNA is not destroyed, can be accessed repeatedly from its storage (i.e. database). Rutten et al. teach that DNA can be modified, amplified and is stable (page 371, col. 1, par. 2). In these processes taught by Rutten, the DNA may be accessed without destroying the DNA. Sequencing DNA at a single molecule level or in solution by PCR amplification does not destroy the DNA.
Rutten et al. teach, “To prevent this data corruption problem, multiple copies of the DNA strand are often used,” (page 366, col. 2, par. 3)(i.e. wherein the datafile comprises a subset of encoded information corresponding to a portion of the plurality of polynucleotide strands in the database).
Regarding an “overhang” on the double stranded DNA, Dekker et al. teach creating dsRNA molecules with overhangs for efficient hybridization and ligation (Abstract). Dekker et al. teach that the protocols used function on any DNA substrate and allow the user to determine the sequence of the overhangs incorporated; Dekker et al. teach that sticky ends for dsRNA are used for controlled, specific and efficient ligation of dsRNA molecules through hybridization (page 1, col. 1, par. 2).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have applied the method of attaching magnetic beads and moieties to separate DNA as taught by Loehrlein et al. to the method of storing information in DNA as taught by Rutten et al. Loehrlein et al. teach attaching primers to target sequences (par. 0005) wherein the primers may be forward and reverse primers (par. 0006) and that the primers may be coupled with a moiety (par. 0168). Rutten et al. teach forward and reverse primers and a “key” primer attached to the information carrying DNA sequence (i.e. data file). At the time of invention, a practitioner could have added a moiety with a magnetic bead as taught by Loehrlein et al. to the DNA data file as taught by Rutten et al. The predictable result of datafile DNAs with magnetic bead labeled moieties would be achieved. Such a combination is merely a "predictable use of prior art elements according to their established functions." One of ordinary skill could have also substituted the concept of having a primer “key” of Rutten et al. with a magnetic bead carrying moiety as taught by Loehrlein et al. Such would be a simple substitution of one known element for another to obtain predictable results. KSR Int’l 7, 127 S. Ct. at 1740.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the method of separating polynucleotides by magnetic beads as taught by Loehrlein et al. wherein the polynucleotides store information as taught by Rutten et al. with the method of creating an overhang on double stranded polynucleotides as taught by Dekker et al. Dekker et al. provide motivation by teaching that the overhang provides for ligation by hybridization (page 1, col. 1, par. 2). One of ordinary skill would have an expectation of success in combining Loehrlein et al. in view of Rutten et al. with Dekker et al. because Rutten et al. also teach providing an overhang on a DNA sequence as a means of adding additional information or editing the information on the DNA strand. However, the structure of the physical DNA strand “overhang” would be the same as that in Dekker et al.
Regarding claims 24, 26-33 and 37-38
Loehrlein et al. teach double stranded DNA (par. 0049 and 0158) and double or single stranded primers (par. 0133), as in claim 24.
Loehrlein et al. teach biotin and antibody moieties (par. 0162) and streptavidin (par. 0179) and streptavidin coated magnetic beads (par. 0252), as in claim 26.
Rutten et al. teach a single stranded overhand and contacting the database with a key nucleic acid (page 5, Figure 1), as in claim 27.
Rutten et al. teach associating free nucleotides (i.e. an overhang sequence) and polymerizing with a polymerase (page 16-17, connecting par.)(i.e. polynucleotide strand comprises a RNA polymerase promoter sequence, extracting the polynucleotide by extracting the ss overhand using a labeled primer, adding the RNA polymerase), as in claim 28.
Rutten et al. teach that m-RNA acts as a reading template after DNA is copied by the DNA polymerase (page 21, section “Writing by catalytic methods), as in claim 29.
Loehrlein et al. teach a “blocking group” (par. 0039), contacting (i.e. providing a reagent that binds a sequence not occluded by the DNA binding molecule) and target specific primers that include labels such as a “friction moiety” (par. 0010 and 0017) which would aid in magnetic extract like a bead (par. 0044)(i.e. providing a reagent that binds to a sequence not occluded, contacted the data base with the reagent and magnetic bead, and extracting polynucleotide strands), as in claim 30.
Loehrlein et al. teach contacting DNA with a reagent of primers (par. 0006) and polymerase (par. 0018)(i.e. oligonucleotide and/or binding protein), as in claim 31.
Loehrlein et al. teach sequencing (par. 0003 and 0076), as in claim 32.
Rutten et al. sequencing and error correction (page 5, section “Error correction”) (i.e. performing error analysis of sequencing data), as in claims 33.
Rutten et al. teach that storing information in DNA polymers is “durable” (Abstract and page 1, par. 1) and DNA can be copied (page 3, par. 2), as in claims 34.
Regarding archeal histone proteins and guide RNA with dCAS9, as in claims 37-38, these DNA binding molecules are well known in the art as basic proteins that bind to DNA.
Response to Arguments
Applicant's arguments filed 6/2/2026 have been fully considered but they are not persuasive.
Applicants argue (Remarks, page 12) that Rutten acknowledges that polymers such as DNA may offer storage solutions but does not teach or suggest using a random-access primer addressed nucleic acid database that preserves the underlying data pool for repeated retrieval and in place-editing. Applicants argue that Loehrlein and Rutten do not appear to disclose “wherein the data file is repeatedly extracted from the database, wherein the [extraction of the data file] is nondestructive and wherein the data file comprises a subset of encoded information corresponding to a portion of the plurality of polynucleotides strands in the database.”
In response, as set forth above, Rutten et al. teach nondestructive methods for extracting information from DNA. One of ordinary skill would recognize that single molecule sequencing and sequencing that includes PCR amplification does not destroy DNA. Furthermore, Rutten et al. suggests that the DNA can be used again after information is extracted. Specifically, Rutten et al. teach modifying the information on the DNA by introducing “overhangs” (page 370, col. 2, par. 1) for the purpose of editing the information. Rutten et al. also teach that specific sequences can be selected and edited (last sentence, page 370, col. 2, par. 1) which suggests that the DNA is not destroyed after selection and will be accessed again after it is edited with additional information. Furthermore, Rutten et al. also teach, “To prevent this data corruption problem, multiple copies of the DNA strand are often used,” (page 366, col. 2, par. 3). This reads on being able to extract the same file repeatedly because it is copied onto a plurality of DNA strands.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-7035. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Anna Skibinsky/
Primary Examiner, AU 1635
Prosecution Insights