www.uspto.gov
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box 1450
`Alexandria, Virginia 2231371450
`
`15/603,013
`
`05/23/2017
`
`William BANYAI
`
`44854-701402
`
`2258
`
`WILSON, SONSINI, GOODRICH & ROSATI
`650 PAGE MILL ROAD
`PALO ALTO, CA 94304-1050
`
`HAMMELL NEIL P
`
`ART UNIT
`
`1636
`
`PAPER NUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`06/26/2019
`
`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.
`15/603,013
`Examiner
`NEIL P HAMMELL
`
`Applicant(s)
`BANYAI et al.
`Art Unit
`1636
`
`AIA (FITF) Status
`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 g 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 09 May 2019.
`[:1 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2a)D This action is FINAL.
`
`2b)
`
`This action is non-final.
`
`3)[:] 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)
`
`1—7,9—10,12—13 and 17—23 is/are pending in the application.
`
`5a) Of the above claim(s)
`
`is/are withdrawn from consideration.
`
`E] Claim(s)
`
`is/are allowed.
`
`Claim(s) 1—7,9—10,12—13 and 17—23 is/are rejected.
`
`[:1 Claim(s)
`
`is/are objected to.
`
`) ) ) )
`
`6 7
`
`8
`
`
`
`are subject to restriction and/or election requirement
`[j Claim(s)
`9
`* If any claims have been determined aflowabie. 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
`
`http://www.uspto.gov/patents/init events/pph/index.jsp or send an inquiry to PPeredback@uspto.gov.
`
`Application Papers
`10)[:] The specification is objected to by the Examiner.
`
`11)[:] The drawing(s) filed on
`
`is/are: a)D accepted or b)l:] objected to by the Examiner.
`
`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)D All
`
`b)I:I Some**
`
`c)CI None of the:
`
`1.[:] Certified copies of the priority documents have been received.
`
`2.[:] Certified copies of the priority documents have been received in Application No.
`
`3.[:] 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)
`
`Notice of References Cited (PTO-892)
`
`Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`2)
`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 20190612
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 2
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`DETAILED CORRESPONDENCE
`
`Notice ofPre-AIA orAIA Status
`
`1.
`
`The present application, filed on or after March 16, 2013, is being examined under the first
`
`inventor to file provisions of the AIA.
`
`Continued Examination Under 37 CFR 1.114
`
`2.
`
`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 1.1 14.
`
`Applicant's submission filed on May 9, 2019 has been entered.
`
`Application Status
`
`3.
`
`This action is written in response to applicant's correspondence received May 9, 2019.
`
`Claims 1-7, 9, 10, 12, 13, 17-20, and 22-28 are currently pending and under examination.
`
`4.
`
`Any rejection or objection not reiterated herein has been overcome by amendment
`
`Applicant's amendments and arguments have been thoroughly reviewed, but are not persuasive to
`
`place the claims in condition for allowance for the reasons that follow.
`
`5.
`
`35 U.S.C. 101 reads as follows:
`
`Claim Rejections - 35 USC § 101
`
`Whoever invents or discovers any new and useful process, machine, manufacture, or
`composition of matter, or any new and useful improvement thereof, may obtain a
`patent therefor, subject to the conditions and requirements of this title.
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 3
`
`6.
`
`Claims 1-7, 9, 10, 12, 13, 17-20, and 22-28 are rejected under 35 U.S.C. 101 because the
`
`claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or
`
`an abstract idea) without significantly more. The claims are directed to a nucleic acid cDNA library
`
`comprising nucleic acids, which are nature-based products. The recitation that the nucleic acids
`
`“encode cDNA sequences with an aggregate error rate ofless than 1 in 800 bases" and “wherein the
`
`nucleic acids comprise subsets ofnucleic acids, and wherein each ofthe subsets of nucleic acids
`
`comprises nucleic acids: (i) varying within a range oflengths; (ii) collectively spanning atleast 0.5
`
`kb in length; and (iii) collectively encoding cDNA sequence for one of the at least 1000 genes" does
`
`not refer to any markedly different characteristic that distinguishes the nucleic acids from their
`
`naturally occurring counterparts in exons of genomic DNA that naturally occur in naturally
`
`occurring genomes. The recitation that the nucleic acids are “synthesized based on instructions
`
`provided in a computer readable non-transient medium" refers to a process of making the claimed
`
`product However, this process of “synthesis" does not result in a product that is markedly different
`
`from its naturally occurring counterpart Accordingly, claim 1 is directed to a product of nature.
`
`There are no elements that are recited in addition to the product of nature of claim 1. Accordingly,
`
`claim 1 is directed to a patent ineligible product of nature without significantly more.
`
`Claims 2-7, 9, 10, 12, 13, 17-20, and 22-28 similarly do not recite any markedly different
`
`characteristic and either do not recite any elements in addition to the products of nature or the
`
`additional elements recited by the claims do not add significantly more to the products of nature
`
`themselves. For example, although claims 12 and 13 recite wherein the nucleic acids are attached to
`
`a structure, the attachment of such cDNA molecules to arrays (i.e. a solid support) was routine and
`
`conventional in the art In addition, claims 17-20 refer to the process by which the nucleic acids are
`
`made, which fails to specify a markedly different characteristic for the synthesized nucleic acid
`
`product itself. Although claim 24 recites “wherein each ofthe nucleic acids comprises at least one
`
`barcode sequence for identification of each of said nucleic acids", it is noted that the specification
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 4
`
`does not define the term “barcode". The claimed “barcode sequence" is also not limited to any
`
`particular nucleotide sequence structure or length, for example. The specification does not provide
`
`guidance for how the “barcode sequence" differs from any given genomic DNA sequence adjacent to
`
`an mRNA—encoding genomic DNA sequence or why such genomic DNA sequence could not be used
`
`to identify its adjacent mRNA-encoding genomic DNA sequence. Rather, such genomic DNA
`
`sequence could be used to identify its neighboring mRNA-encoding genomic DNA sequence.
`
`Accordingly, the recitation “wherein each of the nucleic acids comprises at least one barcode
`
`sequence for identification of each of said nucleic acids" does not require a markedly different
`
`characteristic for the nucleic acid cDNA library.
`
`When the claims are considered as a whole, the claims are directed to naturally occurring
`
`nucleic acids without markedly different characteristics and without additional elements that add
`
`significantly more.
`
`For these reasons the claims are rejected under section 101 as being directed to non-
`
`statutory subject matter.
`
`Response to Arguments
`
`To the extent that Applicant's remarks pertain to the current rejections of the current
`
`claims, Applicants argue that the incorporation of the language ofpreviously pending claim 21
`
`regarding each gene comprising “atleast one intron" into claim 1 would overcome the 101 rejection
`
`and such language is not reflected in amended independent claim 1 (see remarks on page 5).
`
`This argument has been fully considered but is not persuasive because claim 1 was
`
`additionally amended to recite “wherein the nucleic acids comprise subsets of nucleic acids, and
`
`wherein each of the subsets of nucleic acids comprises nucleic acids: (i) varying within a range of
`
`lengths; (ii) collectively spanning at least 0.5 kb in length; and (iii) collectively encoding cDNA
`
`sequence for one ofthe at least 1000 genes". The recitation that the nucleic acids “comprise subsets
`
`of nucleic acids" and further that each ofthe subsets of nucleic acids comprise nucleic acids that
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 5
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`“collectively spanning at least 0.5 kb in lengt " broadens the subject matter of the claim with
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`respect to the length ofthe nucleic acids such that the claim broadly encompasses short exonic
`
`fragments of genomic DNA of even at least 1000 genes comprising at least one intron.
`
`7.
`
`The following is a quotation of 35 U.S.C. 112(b):
`
`Claim Rejections - 35 USC § 112
`
`(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.
`
`8.
`
`Claims 1-7, 9, 10, 12, 13, 17-20, and 22-28 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.
`
`Claim 1 recite “wherein the nucleic acids comprise subsets of nucleic acids, and wherein
`
`each ofthe subsets of nucleic acids comprises nucleic acids: (i) varying within a range oflengths".
`
`The recitation “varying within a range of lengths" is ambiguous because it fails to specify what
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`“range oflengths" the lengths of nucleic acids is required to vary “within". As a result, the metes and
`
`bounds ofthe claim with respect to the lengths of the nucleic acids is unclear. The same rationale is
`
`applicable to claim 28.
`
`Claims 2-7, 12, 17, 23-27 recite “the nucleic acids". However, claim 1 refers to “A nucleic
`
`acid cDNA library comprising nucleic acids...wherein the nucleic acids encode cDNA sequences" and
`
`further “wherein the nucleic acids comprise subsets of nucleic acids, and wherein each of the
`
`subsets of nucleic acids comprises nucleic acids". Accordingly, claim 1 sets forth “nucleic acids" on
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 6
`
`two different occasions, each having different limitations. Accordingly, it is not clear which “nucleic
`
`acids" is being referred to by claims 2-7, 12, 17, 23-27.
`
`Claim 9 recites “wherein each of the subsets of nucleic acids comprise nucleic acids
`
`collectively spanning at least 1 kb in length". Claim 10 similarly recites “wherein each of the subsets
`
`of nucleic acids comprises nucleic acids collectively spanning at least 3 kb in length". It is not clear
`
`how these “nucleic acids" relate to the previous recitation of “nucleic acids" that are “collectively
`
`spanning atleast 0.5 kb in lengt ". It is not clear if they are referring to the same nucleic acids or
`
`different nucleic acids.
`
`Claim 25 recites “wherein each ofthe nucleic acids is 80 to 200 base pairs in lengt ". The
`
`term “base pairs" appears to refer to a double-stranded nucleic acid structure in which nitrogenous
`
`bases form Watson-Crick pairs with complementary nitrogenous bases via hydrogen bonds.
`
`However, the claim does not explicitly recite that the nucleic acids of the cDNA library have a
`
`double-stranded structure. Therefore, it is unclear whether claim 25 encompasses a cDNA library in
`
`which each ofthe nucleic acids is 80 to 200 nucleotides in length or whether claim 25 requires a
`
`double-stranded structure.
`
`Those claims identified in the statement of rejection but not explicitly referenced in the
`
`rejection are also rejected for depending from a rejected claim but failing to remedy the
`
`indefiniteness therein.
`
`9.
`
`The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
`
`Claim Rejections - 35 USC § 112
`
`(a) IN GENERAL—The specification shall contain a written description of the
`
`invention, and ofthe manner and process of making and using it, in such full, clear,
`
`concise, and exact terms as to enable any person skilled in the art to which it
`
`pertains, or with which it is most nearly connected, to make and use the same, and
`
`shall set forth the best mode contemplated by the inventor or joint inventor of
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`carrying out the invention.
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 7
`
`The following is a quotation of the first paragraph ofpre-AIA 35 U.S.C. 112:
`
`The specification shall contain a written description of the invention, and of the
`
`manner and process of making and using it, in such full, clear, concise, and exact
`
`terms as to enable any person skilled in the art to which it pertains, or with which it
`
`is most nearly connected, to make and use the same, and shall set forth the best
`
`mode contemplated by the inventor of carrying out his invention.
`
`10.
`
`Claims 1-7, 9, 10, 12, 13, 17-20, and 22-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C.
`
`112 (pre-AIA), first paragraph, as failing to comply with the written description requirement The
`
`claim(s) contains subject matter which was not described in the specification in such a way as to
`
`reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-
`
`AIA the inventor(s), at the time the application was filed, had possession ofthe claimed invention.
`
`This is a NEW MATTER rejection.
`
`MPEP 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support
`
`in the original disclosure for new or amended claims" and “[i]fthe originally filed disclosure does
`
`not provide support for each claim limitation, or if an element which applicant describes as
`
`essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112a,
`
`as lacking adequate written description". According to MPEP § 2163.1.B, "While there is no in haec
`
`verba requirement, newly added claim limitations must be supported in the specification through
`
`express, implicit, or inherent disclosure" and "The fundamental factual inquiry is whether the
`
`specification conveys with reasonable clarity to those skilled in the art that, as of the filing date
`
`sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935
`
`F.2d at 1563-64, 19 USPQ2d at 1117".
`
`In the instantly rejected claims, the new limitation of "genomic sequence" in claims 1 and 28
`
`appears to represent new matter. No specific basis for this limitation was identified in the
`
`specification, nor did a review of the specification by the examiner find any basis for the limitation.
`
`Since no basis has been identified, the claims are rejected as incorporating new matter.
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`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 8
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`Withdrawn Claim Rejections - 35 USC§ 103
`
`11.
`
`The rejections of claims 1-7, 9, 10, and 17-23 under 35 U.S.C. 103 as being unpatentable
`
`over Gao (Gao et al. (2002) PNAS, 99(20):12612-12616) in view ostieh (US 2010/0099103) is
`
`withdrawn in view of the amendments to the claims.
`
`12.
`
`The rejections of claims 1-7, 9, 10, 17, 19, and 21-23 under 35 U.S.C.103 as being
`
`unpatentable over Baynes (US 2008/02 87320, herein referred to as “Baynes ‘320") in view of Gao
`
`(Gao et al. (2002) PNAS, 99(20):12612-12616), and Hsieh (US 2010/0099103) is withdrawn in
`
`view of the amendments to the claims. The prior art rejections set forth below are applicable to the
`
`current claims.
`
`Claim Rejections - 35 USC § 103
`
`13.
`
`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
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`basis 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.
`
`14.
`
`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
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`each claim that was not commonly owned as ofthe 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.
`
`15.
`
`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
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 9
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`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.
`
`16.
`
`Claims 1-7, 12, 13, 17-20, and 25-28 are rejected under 35 U.S.C. 103 as being unpatentable
`
`over Baynes (US 2008/02 87320, herein referred to as “Baynes ‘320") in view of Gao (Gao et al.
`
`(2002) PNAS, 99(20):12612-12616), as evidenced by Cruse (Cruse et al. "Atlas ofImmunology,
`
`Third Edition". Boca Raton:CRC Press, 2010. Pages 261-265, 282-283).
`
`Baynes ‘320 describes a nucleic acid library, wherein the library contains nucleic acids that
`
`are assembled from oligonucleotides (i.e. subsets of nucleic acids) synthesized on a solid support
`
`([0180]). Regarding (i), Baynes ‘320 teaches that the oligonucleotides (i.e. subsets of nucleic acids)
`
`can be ofany length, but is typically 40-200 bases long ([0098]) and therefore teaches that the
`
`lengths ofthe oligonucleotides can vary. Baynes ‘320 further teaches wherein the oligonucleotides
`
`are synthesized to form a stem-loop structure ([0091]) in which the length of the stem of the
`
`oligonucleotides have differentlengths and can range from about 20 to about 100 or more
`
`nucleotides long (i.e. varying within a range oflengths) ([0101]). Regarding (ii), Baynes ‘320
`
`teaches wherein the oligonucleotides assemble to form nucleic acids of any size of interest
`
`including 500-1000 or 1000-10000, for example (i.e. collectively spanning at least 0.5 kb in length)
`
`([0116]).
`
`Baynes ‘320 does teach wherein the nucleic acids may have been obtained from cDNA
`
`([005 8]), but does not teach that the cDNA library is “collectively encoding for at least 1000 genes,
`
`wherein each of the atleast 1000 genes is a different genomic sequence that comprises atleast one
`
`intron" such that the oligonucleotides are “(iii) collectively encoding cDNA sequence for one of the
`
`at least 1000 genes".
`
`However, Baynes ‘320 teaches that the libraries of the invention may be an expression
`
`library such as a phage display library in which each nucleic acid corresponds to a polypeptide
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 10
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`whose function is screened ([0174]). Baynes ‘320 specifically teaches that the synthetic nucleic
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`acids may be provided as libraries for screening in research and development such as for potential
`
`therapeutic proteins ([0205]).
`
`In addition, Gao teaches that combinatorial antibody library technology represents a
`
`powerful tool for discovering and designing antibodies that bind targets with high affinity and
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`specificity that obviate the need for immunization and laborious protocols (see page 12612, column
`
`1, paragraph 1). Gao describes a combinatorial antibody library comprising cDNA sequences (page
`
`12613, column 1, paragraph 3), wherein the library comprises members that correspond to 4.5 X
`
`109 genes (page 12614, column 1, paragraph 2). Gao further teaches that the combinatorial
`
`antibody library is useful for screening for antibodies specific for various endogenous factors and
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`exogenous toxins for passive immunotherapy of disease and for protection (page 12616, column 1).
`
`It would have been obvious to one ofordinary skill in the art to have applied the nucleic
`
`acid library ofBaynes ‘320 to synthesize a combinatorial antibody library comprising cDNA
`
`sequences as described by Gao because it would have merely amounted to a simple combination of
`
`prior art elements according to known methods to yield predictable results. One would have been
`
`motivated to do so for the advantage of achieving the benefits of such combinatorial antibody
`
`libraries as discussed by Gao such as for screening for potentially therapeutic antibodies. In
`
`addition, since Baynes ‘320 teaches that the members of the nucleic acid library are intended to be
`
`representative of a plurality ofpredetermined nucleic acids of interest ([0030]), one would have
`
`had a reasonable expectation of success in designing the nucleic acid library ofBaynes ‘320 to
`
`reproduce the combinatorial antibody library of Gao.
`
`Regarding the recitation that “each of the at least 1000 genes is a different genomic
`
`sequence that comprises at least one intron", Gao teaches that the cDNA sequences in the nucleic
`
`acid library encode VH and VL sequences obtained from peripheral blood lymphocytes (see page
`
`

`

`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 11
`
`12613, column 1, paragraphs 2 and 3). However, Gao does not teach whether the immunoglobulin
`
`genes comprise atleast one intron. However, Cruse describes the presence ofintrons in
`
`immunoglobulin genes to which the cDNA sequences correspond (see Fig 7.94). Therefore, it is
`
`inherent to such immunoglobulin genes that they comprise introns.
`
`Regarding the recitation of “preselected cDNA sequences" and “wherein the nucleic acids
`
`encode cDNA sequences with an aggregate error rate ofless than 1 in 800 bases", it is noted that the
`
`structure of the “preselected cDNA sequences" and the cDNA sequences in the nucleic acid library
`
`are unlimited. In addition, the recitation “wherein the nucleic acids encode cDNA sequences with an
`
`aggregate error rate ofless than 1 in 800 bases" broadly encompasses wherein the cDNA sequences
`
`in the nucleic acid library are identical to the preselected cDNA sequences. One could sequence
`
`each cDNA sequence in Gao's library to generate a list of cDNA sequences that accurately represent
`
`the cDNA sequences in the library. Given such a list of cDNA sequences that are identical to the
`
`cDNA sequences in the cDNA library, the cDNA sequences in the cDNA library would comprise an
`
`aggregate error rate of zero (i.e. less than 1 in 800 bases) relative to this list ochNA sequences.
`
`The recitation that the “cDNA sequences" in the “instructions" are “preselected" amounts to non-
`
`functional descriptive material that is not sufficient to distinguish such a set of cDNA sequences that
`
`are not “preselected". Attempting to define the set ochNA sequences in the nucleic acid library as
`
`compared to another set of cDNA sequences which are undefined and unlimited is not sufficient to
`
`distinguish the claim from the prior art
`
`In addition, the additional recitations that the nucleic acids are “synthesized based on
`
`instructions provided in a computer readable non-transient medium, wherein the instructions
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`comprise a list of preselected cDNA sequences" or “wherein the nucleic acids encode cDNA
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`sequences with an aggregate error rate ofless than 1 in 800 bases compared to the preselected
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`cDNA sequences received in the instructions provided in the computer readable non-transient
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`

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`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 12
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`medium", these elements refer to the process by which the claimed cDNA library is made. MPEP
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`2113 makes clear that “Product-by-process claims are notlimited to the manipulations of the
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`recited steps, only the structure implied by the steps" when evaluating such claims in view of the
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`prior art The structural limitations ofthe nucleic acids ofthe cDNA library are addressed above
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`and are sufficient to meet the claim as a whole. As a result, the process limitations as identified
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`above fail to distinguish the claim from the prior art.
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`Nevertheless, in the event that one did carry out a process of synthesizing the nucleic acids
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`based on “preselected" cDNA sequences, Baynes ‘320 teaches wherein less than 0.001% oflibrary
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`members contain a sequence error ([0046]). Baynes ‘320 teaches achieving this low error rate by
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`carrying out steps that correct for errors (see [0080]—[009 6], for example). Baynes ‘320 teaches
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`that after such error correction steps, the resulting library may contain less 1/2000 errors per base
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`(i.e. less than 1 error in 2000 bases) ([0187]). It would have been obvious to have applied such
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`error correction steps for the advantage of achieving a nucleic acid library that is substantially free
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`of errors and therefore more accurately represents the intended sequences thereby reducing the
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`aggregate error rate to less than 1 in 1000 or less than 1 in 2000 bases (i.e. less than 1 in 800
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`bases).
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`To the extent that Gao does not explicitly teach the length of the cDNA sequences encoding
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`the scFv antibody fragments or the number of amino acids in the scFv fragments, Cruse teaches that
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`ScFv is a single-chain molecule comprised of both heavy and light chain variable regions fastened
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`together by a flexible linker (see page 242, column 1, paragraph 1). Cruse further teaches that each
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`immunoglobulin domain is comprised of approximately 110 amino acid residues (see page 244,
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`column 2). Accordingly, it is inherent to the scFv of Gao that they each comprise approximately 22 0
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`amino acid residues, which is encoded by approximately 660 nucleotides (i.e. atleast 0.5 kb in
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`length).
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`

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`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 13
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`Regarding claim 2, requiring a particular “error rate" for the nucleic acids which is
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`determined relative to “preselected cDNA sequences", wherein the “preselected cDNA sequences"
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`are undefined and therefore unlimited is not sufficient to distinguish the claim from the prior art.
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`Nevertheless, the embodiment in which errors in the nucleic acids are corrected such that the error
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`rate is reduced to less than 1 in 1000 bases is discussed above as applied to claim 1.
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`Regarding claim 3, Baynes ‘320 teaches wherein the nucleic acid library is “isolated"
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`q0198D.
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`Regarding claim 4, Baynes ‘320 teaches wherein the nucleic acid library is “purified"
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`q0198D.
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`Regarding claims 5-7, Baynes ‘320 teaches wherein the library may comprise 10,000,000
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`different members ([0044]). To the extent that Baynes ‘320 does not explicitly teach that such
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`different members are cDNA sequences encoding for as many genes, Gao teaches wherein the cDNA
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`library contains members that correspond to 4.5 X 109 genes (page 12614, column 1, paragraph 2)
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`as discussed above. The obviousness of making a cDNA library as described by Gao in the manner
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`described by Baynes ‘320 is discussed above as applied to claim 1.
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`Regarding claims 12 and 13, Baynes ‘320 teaches wherein the oligonucleotides are attached
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`to a solid support ([0180]).
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`Regarding claims 17-20, claim 17 recites “wherein the nucleic acids are synthesized by a
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`process comprising chemical synthesis on a solid support", which refers to the process by which the
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`

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`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 14
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`nucleic acids of the claimed cDNA library are made. Claims 18-20 further limit the process by which
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`the nucleic acids are made. However, the process of“chemical synthesis" as recited by claim 17, the
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`recitation wherein the solid support “comprises a plurality of molecules bound to the solid support
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`at loci, and wherein the plurality of molecules comprise a reactive group capable ofcoupling to a
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`nucleoside" as recited by claim 18, the recitation “wherein the solid support is a plate" as recited by
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`claim 19, and the recitation “wherein the solid support comprises silicon, polypropylene, or
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`polydimethylsiloxane (PDMS)" as recited by claim 20 are not sufficient to limit the structure of the
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`claimed nucleic acid cDNA library.
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`Nevertheless, regarding claim 17, Baynes ‘320 teaches wherein the nucleic acids are
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`synthesized by a process comprising chemical synthesis on a solid support ([0180]). Regarding
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`claim 18, Baynes ‘320 teaches wherein the solid support comprises cleavable linker moieties (i.e.
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`molecules comprising reactive groups) that are capable of attaching to the 5' or 3' end of the
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`oligonucleotide ([0180]). Regarding claim 19, Baynes ‘320 teaches wherein the solid support
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`comprises a plate ([0180]).
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`Regarding claim 25, Baynes ‘320 teaches that the oligonucleotides (i.e. subsets of nucleic
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`acids) can be of any length, but is typically 40-200 bases long ([0098]), which describes with
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`sufficient specificity the claimed range of“80 to 200 base pairs in length" because the claimed range
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`“80 to 200 base pairs in length" is entirely encompassed by the teaching “40-200 bases long" and
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`because there is no evidence ofthe criticality ofthe more narrow claimed range which does not
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`encompass the range of40-79 bases. In addition, Baynes ‘320 additionally teaches the preferred
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`embodiments in which stem-loop oligonucleotides comprise a loop that is 3-10 nucleotides in
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`length ([0094]), wherein the stem elements of the stem-loop oligonucleotides is “about 50"
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`nucleotides long ([0101]), which sufficiently teaches oligonucleotides that are about 110-1 13
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`nucleotides in length, which anticipates the claimed range of“80 to 200".
`
`

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`Application/Control Number: 15/603,013
`Art Unit: 1636
`
`Page 15
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`Regarding claim 26, Baynes ‘320 does not explicitly teach “wherein the nucleic acids varying
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`within a range oflengths are of atleast 10 differentlengths".
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`However, Baynes ‘320 teaches that the oligonucleotides (i.e. subsets of nucleic acids) can