www.uspto.gov
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`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box 1450
`Alexandria, Virginia 2231371450
`
`15/952,203
`
`04/12/2018
`
`Timothy A. Blauwkamp
`
`47697-709201
`
`6884
`
`WILSON, SONSINI, GOODRICH & ROSATI
`650 PAGE MILL ROAD
`PALO ALTO, CA 94304-1050
`
`STRZELECKA~ TERESA E
`
`ART UNIT
`
`1637
`
`PAPER NUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`08/20/2019
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
`
`following e—mail address(es):
`
`patentdoeket@ wsgroom
`
`PTOL-90A (Rev. 04/07)
`
`

`

`0/7709 A0170” Summary
`
`Application No.
`15/952,203
`Examiner
`TERESA E STRZELECKA
`
`Applicant(s)
`Blauwkamp et al.
`Art Unit
`AIA (FITF) Status
`1637
`Yes
`
`- The MAILING DA TE of this communication appears on the cover sheet wit/7 the correspondence address -
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 2 MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed after SIX (6) MONTHS from the mailing
`date of this communication.
`|f NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any earned patent term
`adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1)[:] Responsive to communication(s) filed on
`[:1 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2a)D This action is FINAL.
`
`2b)
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`This action is non-final.
`
`3)C] An election was made by the applicant in response to a restriction requirement set forth during the interview on
`; the restriction requirement and election have been incorporated into this action.
`
`4):] Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Expat/7e Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`5)
`Claim(s)
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`115—151 is/are pending in the application.
`
`5a) Of the above claim(s)
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`is/are withdrawn from consideration.
`
`[:1 Claim(s) _ is/are allowed.
`
`[3 Claim(s)
`
`is/are rejected.
`
`C] Claim(s) _
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`is/are objected to.
`
`) ) ) )
`
`6 7
`
`8
`
`
`
`Claim(s) 115—151 are subject to restriction and/or election requirement
`9
`* If any claims have been determined aflowabte, you may be eligible to benefit from the Patent Prosecution Highway program at a
`
`participating intellectual property office for the corresponding application. For more information, please see
`
`httpfiwww.”smogovmatentszinit_events[pph[index.'sp or send an inquiry to PPeredhack@g§ptg.ggv.
`
`Application Papers
`
`10):] The specification is objected to by the Examiner.
`
`is/are: a)D accepted or b)D objected to by the Examiner.
`11):] The drawing(s) filed on
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`12)[:] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`
`a)I:J All
`
`b)D Some”
`
`c)D None of the:
`
`1E] Certified copies of the priority documents have been received.
`
`2.[:] Certified copies of the priority documents have been received in Application No.
`
`3.0 Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`
`1) C] Notice of References Cited (PTO-892)
`
`2) E] Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`Paper No(s)/Mail Date_
`U.S. Patent and Trademark Office
`
`3) C] Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`4) CI Other-
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20190816A
`
`

`

`Application/Control Number: 15/952,203
`Art Unit: 1637
`
`Page 2
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`DETAILED ACTION
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`Notice ofPre-AIA 0r AIA Status
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`1.
`
`The present application, filed on or after March 16, 2013, is being examined under the
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`first inventor to file provisions of the AIA.
`
`Election/Restriction
`
`2.
`
`Restriction to one of the following inventions is required under 35 U.S.C. 121:
`
`1. Claims 115—136, drawn to a method for performing a primer extension reaction on
`
`RNA and DNA, comprising:
`
`a) providing a sample comprising a mixture of single—stranded DNA and single—stranded
`
`RNA;
`
`b) attaching a first adapter to said single—stranded DNA,
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`c) attaching a second adapter to said single—stranded RNA;
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`d) annealing a first primer to said first adapter and annealing a second primer to said
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`second adapter;
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`e) extending said annealed first primer on said single—stranded DNA to form double—
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`stranded DNA; and
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`f) extending said annealed second primer on said single—stranded RNA to form a double—
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`stranded DNA—RNA hybrid, classified in C12Q 1/6855, for example.
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`11. Claims 137—143, drawn to a method of performing an amplification reaction on a first
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`RNA and a first DNA, comprising:
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`a) providing a sample comprising a mixture of said first DNA and said first RNA,
`
`wherein said first DNA does not comprise a sequence complementary to said first RNA;
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`b) tagging said first DNA with a first tag Without using a transposase;
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`

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`Application/Control Number: 15/952,203
`Art Unit: 1637
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`Page 3
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`c) tagging said first RNA with a second tag;
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`d) performing an amplification or primer extension reaction on said first DNA with a
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`polymerase that is selective for DNA templates; and
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`e) synthesizing a complementary cDNA strand from said first RNA with a reverse
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`transcriptase, classified in C12Q 1/6806, for example.
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`111. Claim 144, drawn to a method of sequencing nucleic acids comprising:
`
`a) providing a sample comprising double—stranded nucleic acids and single—stranded
`
`nucleic acids;
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`b) ligating a first adapter to an end of said double—stranded nucleic acids;
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`c) denaturing said double—stranded nucleic acids into single—stranded nucleic acids; and
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`d) sequencing nucleic acids ligated to said first adapter and identifying sequences
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`associated with said first adapter as being double—stranded, classified in C12Q 1/6869, for
`
`example.
`
`IV. Claim 145, drawn to a method for concurrent processing of different nucleic acid
`
`forms in a sample comprising:
`
`a) denaturing said nucleic acid forms in a sample;
`
`b) ligating a first adapter to one end of a first nucleic acid form using a ligase that has a
`
`preference for said first nucleic acid form and ligating a second adapter to one end of a second
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`nucleic acid form using a ligase that has preference for said second nucleic acid form;
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`c) primer extending said first and said second ligated nucleic acid forms;
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`d) ligating a third adapter comprising a priming element; and
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`e) amplifying said first and second nucleic forms, classified in C12Q 1/6809, for
`
`example.
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`

`

`Application/Control Number: 15/952,203
`Art Unit: 1637
`
`Page 4
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`V. Claim 146 and 148, drawn to reaction mixture composition and a kit comprising: a) an
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`adapter; b) a first ligase that has a preference for a first nucleic acid form; c) a second ligase that
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`has a preference for a second nucleic acid form; and d) a buffer, classified in C12N 9/93, for
`
`example.
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`VI. Claim 147 and 149, drawn to a reaction mixture and a kit comprising: a) a ligase; b) a
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`DNA—dependent polymerase that has non—templated activity, wherein said non—templated base is
`
`N1; and c) a RT polymerase that has non—templated actiVity, wherein said non—templated base is
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`N2, wherein N1 and N2 are different nucleic acid bases, classified in C12N 19/1247, for
`
`example.
`
`VII. Claim 150, drawn to a method of sequencing different nucleic acids forms
`
`comprising:
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`a) providing a sample comprising different nucleic acid forms;
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`b) denaturing said nucleic acid forms in a sample;
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`c) ligating a first adapter to one end of a first nucleic acid form using a ligase that has a
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`preference for said first nucleic acid form; and ligating a second adapter to one end of a second
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`nucleic acid form using a ligase that has preference for said second nucleic acid form, wherein
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`said first and said second adapter comprise different identifying sequences; and
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`d) sequencing said ligated nucleic acids, thereby identifying said different nucleic acid
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`forms in said sample, classified in C12Q 1/6869, for example.
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`VIII. Claim 151, drawn to a method for processing different nucleic acid forms in a
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`sample comprising:
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`a) denaturing said different nucleic acid forms in a sample, wherein said different nucleic
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`acid forms comprise a first nucleic acid form and a second nucleic acid form;
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`

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`Application/Control Number: 15/952,203
`Art Unit: 1637
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`Page 5
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`b) attaching a first adapter to said first nucleic acid form and a second adapter to said
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`second nucleic acid form;
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`c) amplifying said first nucleic acid form using a DNA—dependent polymerase that has
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`non—templated activity, wherein said non—templated activity comprises adding at least one N1
`
`nucleotide or a first sequence to amplified products of said amplification of said first nucleic acid
`
`form; and
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`d) amplifying said second nucleic acid form using a reverse transciptase polymerase that
`
`has non—templated activity, wherein said non—templated activity comprises adding at least one N2
`
`nucloetide or a second sequence to amplified products of said amplification of said second
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`nucleic acid form, wherein said N1 nucleotide and said N2 nucleotide are different nucleotides or
`
`said first sequence is different from said second sequence, classified in Cl2Q 1/6844, for
`
`example.
`
`The inventions are independent or distinct, each from the other because:
`
`3.
`
`Inventions I—IV, VII and VIII are unrelated. Inventions are unrelated if it can be shown
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`that they are not disclosed as capable of use together and they have different designs, modes of
`
`operation, and effects (MPEP § 802.01 and § 806.06). In the instant case, the different
`
`inventions are methods with different goals, method steps and materials.
`
`The method of performing a primer extension reaction (Group I), the method of
`
`performing an amplification reaction (Group II), the method of sequencing (Group III), the
`
`method of concurrent processing of different nucleic acid forms (Group IV), the method of
`
`sequencing different nucleic acid forms (Group VII) and the method of processing different
`
`nucleic acid forms (Group VIII) are all unrelated as they comprise distinct steps and utilize
`
`different products which demonstrates that each method has a different mode of operation. Each
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`

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`Application/Control Number: 15/952,203
`Art Unit: 1637
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`Page 6
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`invention performs this function using a structurally and functionally divergent material. For
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`these reasons the Inventions I—IV, VII and VIII are patentably distinct. Furthermore, the distinct
`
`steps and products require separate and distinct searches. The inventions of Groups I—IV, VII and
`
`VIII have a separate status in the art as shown by their different classifications. As such, it
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`would be burdensome to search the inventions of Groups I—IV, VII and VIII together.
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`4.
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`Inventions V and (I—IV, VII and VIII) are unrelated. Inventions are unrelated if it can be
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`shown that they are not disclosed as capable of use together and they have different designs,
`
`modes of operation, and effects (MPEP § 802.01 and § 806.06). In the instant case, the
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`composition and kit of Group V are not required for the methods of Groups I—IV, VII and VIII.
`
`5.
`
`Inventions VI and (I—IV, VII and VIII) are unrelated. Inventions are unrelated if it can be
`
`shown that they are not disclosed as capable of use together and they have different designs,
`
`modes of operation, and effects (MPEP § 802.01 and § 806.06). In the instant case, the
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`composition and kit of Group VI are not required for the methods of Groups I—IV, VII and VIII.
`
`6.
`
`Restriction for examination purposes as indicated is proper because all the inventions
`
`listed in this action are independent or distinct for the reasons given above @ there would be a
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`serious search and/or examination burden if restriction were not required because one or more of
`
`the following reasons apply:
`
`Because these inventions are distinct for the reasons given above, have acquired a
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`separate status in the art as shown by their different classification, and the search required for
`
`each group is not required for the other groups because each group requires a different non—
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`patent literature search due to each group comprising different products and/or method steps,
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`restriction for examination purposes as indicated is proper.
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`

`

`Application/Control Number: 15/952,203
`Art Unit: 1637
`
`Page 7
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`Applicant is advised that the reply to this requirement to be complete must include
`
`(i) an election of a invention to be examined even though the requirement may be traversed (37
`
`CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
`
`The election of an invention may be made with or without traverse. To reserve a right to
`
`petition, the election must be made with traverse. If the reply does not distinctly and specifically
`
`point out supposed errors in the restriction requirement, the election shall be treated as an
`
`election without traverse. Traversal must be presented at the time of election in order to be
`
`considered timely. Failure to timely traverse the requirement will result in the loss of right to
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`petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate
`
`which of these claims are readable upon the elected invention.
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`Should applicant traverse on the ground that the inventions are not patentably distinct,
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`applicant should submit evidence or identify such evidence now of record showing the
`
`inventions to be obvious variants or clearly admit on the record that this is the case. In either
`
`instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence
`
`or admission may be used in a rejection under 35 U.S.C. 103 or pre—AIA 35 U.S.C. 103(a) of the
`
`other invention.
`
`7.
`
`This application contains claims directed to the following patentably distinct species:
`
`Group I
`
`Species of a 1igase for the first adapter
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`A) CircLigase 11 (claim 117),
`
`B) Thermostable App—DNA/RNA 1igase (claim 117),
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`C) T4 RNA 1igase (claim 117),
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`D) T4 RNA Ligase 2 truncated (claim 117),
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`

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`Page 8
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`Application/Control Number: 15/952,203
`Art Unit: 1637
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`E) a combination of ligases (claim 117).
`
`Species of a sample
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`F) blood (claim 122),
`
`G) plasma (claim 122),
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`H) serum (claim 122),
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`I) cerebrospinal fluid (claim 122),
`
`J) synovial fluid (claim 122),
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`K) bronchio—alveolar lavage (claim 122),
`
`L) urine (claim 122),
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`M) stool (claim 122),
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`N) saliva (claim 122),
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`O) nasal swab (claim 122),
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`P) a combination of samples (claim 122).
`
`Species of further method steps
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`Q) further comprising adding at least one non—templated nucleotide to a first primer extension
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`strand (claims 126—132),
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`R) further comprising adding at least one second non—templated nucleotide to a second primer
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`extension strand forming a second overhang (claim 133),
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`S) further comprising hybridizing a third adapter to said first overhang and a fourth adapter to
`
`said second overhang (claim 134),
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`T) further comprising sequencing said third adapter and said fourth adapter and sequences
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`attached to said third adapter and said fourth adapter (claim 135),
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`

`

`Application/Control Number: 15/952,203
`Art Unit: 1637
`
`Page 9
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`U) further comprising (i) identifying sequences associated with said third adapter as originating
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`from said DNA in said mixture of single—stranded DNA and single—stranded RNA and (ii)
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`identifying sequences associated with said fourth adapter as originating from said RNA in said
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`mixture of single—stranded DNA and single—stranded RNA (claim 136).
`
`S ecies of at least one non—tem lated nucleotide if s ecie
`
`is elected
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`V) said at least one non—templated nucleotide is a deoxycytidine (claim 127),
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`W) said at least one non—templated nucleotide is added to a 3' end (claim 128),
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`X) said at least one non—templated nucleotide is up to eight nucleotides (claim 129),
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`Y) said at least one non—templated nucleotide is three non—templated nucleotides (claim 130),
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`Z) said at least one non—templated nucleotide is four non—templated nucleotides (claim 130),
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`AA) said at least one non—templated nucleotide is five non—templated nucleotides (claim 130),
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`AB) said at least one non—templated nucleotide is one non—templated nucleotide (claim 131),
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`AC) said at least one non—templated nucleotide forms a first overhang (claim 132).
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`Group II
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`Species of first DNA
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`A) single—stranded DNA (claim 138),
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`B) double—stranded DNA (claim 138),
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`C) triple—stranded DNA (claim 138),
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`D) a Holliday junction (claim 138),
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`E) cell—free DNA (claim 140).
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`Species of first RNA
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`F) single—stranded RNA (claim 139),
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`G) double—stranded RNA (claim 139),
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`

`

`Application/Control Number: 15/952,203
`Art Unit: 1637
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`H) a ribozyme (claim 139).
`
`Page 10
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`Species of a sample
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`1) blood (claim 141),
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`J) plasma (claim 141),
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`K) serum (claim 141),
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`L) cerebrospinal fluid (claim 141),
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`M) synovial fluid (claim 141),
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`N) bronchio—alveolar lavage (claim 141),
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`O) urine (claim 141),
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`P) stool (claim 141),
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`Q) saliva (claim 141),
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`R) nasal swab (claim 141),
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`S) a combination of samples (claim 141).
`
`8.
`
`The species are independent or distinct because the claims to the different species recite
`
`the mutually exclusive characteristics of such species. In addition, these species are not obvious
`
`variants of each other based on the current record.
`
`Applicant is required under 35 U.S.C. 121 to elect a single disclosed species from each of
`
`the sets of species if Group I or Group II is elected, or a single grouping of patentably indistinct
`
`species, for prosecution on the merits to which the claims shall be restricted if no generic claim is
`
`finally held to be allowable. Currently, claims 115 and 137 are generic.
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`There is a search and/or examination burden for the patentably distinct species as set
`
`forth above because at least the following reason(s) apply:
`
`

`

`Application/Control Number: 15/952,203
`Art Unit: 1637
`
`Page 11
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`The species require a different field of search (e. g., searching different classes/subclasses
`
`or electronic resources, or employing different search queries); and/or the prior art applicable to
`
`one species would not likely be applicable to another species; and/or the species are likely to
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`raise different non—prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
`
`Applicant is advised that the reply to this requirement to be complete must include
`
`(i) an election of a species to be examined even though the requirement may be traversed (37
`
`CFR 1.143) and (ii) identification of the claims encompassing the elected species or
`
`grouping of patentably indistinct species, including any claims subsequently added. An
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`argument that a claim is allowable or that all claims are generic is considered nonresponsive
`
`unless accompanied by an election.
`
`The election may be made with or without traverse. To preserve a right to petition, the
`
`election must be made with traverse. If the reply does not distinctly and specifically point out
`
`supposed errors in the election of species requirement, the election shall be treated as an election
`
`without traverse. Traversal must be presented at the time of election in order to be considered
`
`timely. Failure to timely traverse the requirement will result in the loss of right to petition under
`
`37 CFR 1.144. If claims are added after the election, applicant must indicate which of these
`
`claims are readable on the elected species or grouping of patentably indistinct species.
`
`Should applicant traverse on the ground that the species, or groupings of patentably
`
`indistinct species from which election is required, are not patentably distinct, applicant should
`
`submit evidence or identify such evidence now of record showing them to be obvious variants or
`
`clearly admit on the record that this is the case. In either instance, if the examiner finds one of
`
`the species unpatentable over the prior art, the evidence or admission may be used in a rejection
`
`under 35 U.S.C. 103 or pre—AIA 35 U.S.C. 103(a) of the other species.
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`

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`Application/Control Number: 15/952,203
`Art Unit: 1637
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`Page 12
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`Upon the allowance of a generic claim, applicant will be entitled to consideration of
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`claims to additional species which depend from or otherwise require all the limitations of an
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`allowable generic claim as provided by 37 CFR 1.141.
`
`9.
`
`Applicant is reminded that upon the cancellation of claims to a non—elected invention, the
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`inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the
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`currently named inventors is no longer an inventor of at least one claim remaining in the
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`application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an
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`application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her
`
`legal name and by the processing fee required under 37 CFR 1.17(i).
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`10.
`
`The examiner has required restriction between product or apparatus claims and process
`
`claims. Where applicant elects claims directed to the product/apparatus, and all
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`product/apparatus claims are subsequently found allowable, withdrawn process claims that
`
`include all the limitations of the allowable product/apparatus claims should be considered for
`
`rejoinder. All claims directed to a nonelected process invention must include all the limitations
`
`of an allowable product/apparatus claim for that process invention to be rejoined.
`
`In the event of rejoinder, the requirement for restriction between the product/apparatus
`
`claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be
`
`fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the
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`rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C.
`
`101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an
`
`otherwise proper restriction requirement between product/apparatus claims and process claims
`
`may be maintained. Withdrawn process claims that are not commensurate in scope with an
`
`allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in
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`

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`Application/Control Number: 15/952,203
`Art Unit: 1637
`
`Page 13
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`order for rejoinder to occur, applicant is advised that the process claims should be amended
`
`during prosecution to require the limitations of the product/apparatus claims. Failure to do so
`
`may result in no rejoinder. Further, note that the prohibition against double patenting rejections
`
`of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner
`
`before the patent issues. See MPEP § 804.01.
`
`Conclusion
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to TERESA E STRZELECKA whose telephone number is
`
`(571)272—0789. The examiner can normally be reached on M—F 9—7.
`
`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, Gary Benzion can be reached on 571—272—0782. The fax phone number for the
`
`organization where this application or proceeding is assigned is 571—273—8300.
`
`Information regarding the status of an application may be obtained from the Patent
`
`Application Information Retrieval (PAIR) system. Status information for published applications
`
`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
`
`applications is available through Private PAIR only. For more information about the PAIR
`
`system, see http://pair—direct.uspto.gov. Should you have questions on access to the Private PAIR
`
`system, contact the Electronic Business Center (EBC) at 866—217—9197 (toll—free). If you would
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`Application/Control Number: 15/952,203
`Art Unit: 1637
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`Page 14
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`like assistance from a USPTO Customer Service Representative or access to the automated
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`information system, call 800—786—9199 (IN USA OR CANADA) or 571—272—1000.
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`/TERESA E STRZELECKA/
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`Primary Examiner, Art Unit 1637
`August 16, 2019
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