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 .
DETAILED ACTION
Responsive to communications entered 26AUG2025
Claims Pending 178-180,182-186,188-190,192-193,197-208,210-215
Claims Under Consideration 178-180,182-186,188-190,192-193,197-208,210-215
Priority
This application has a filing date of 05/09/2024 and is a CON of
17/197,796 03/10/2021 PAT 12019077
17/197,796 is a CON of 16/098,436 11/01/2018
16/098,436 is a 371 of PCT/US17/30702 05/02/2017
PCT/US17/30702 has PRO 62/376,886 08/18/2016
PCT/US17/30702 has PRO 62/339,071 05/19/2016
PCT/US17/30702 has PRO 62/330,841 05/02/2016
Maintained Claim Rejection(s) - 35 USC § 103
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 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.
Claims 178-180,182-184,186,188-190,192,193,197,198,200-208,210,211,212,214 are rejected under 35 U.S.C. 103 as being unpatentable over Mikkelsen et al (US PgPub 20160122753; of record) in view of Young et al (US PgPub 20100297693; of record)
Mikkelsen et al teach throughout the document and especially the title and paragraph 0003, high throughput RNA-Seq. More particularly in figures 2-3, paragraphs 0009,0017,0067 and/or 0044 plus the examples, Mikkelsen et al prepares a nucleic acid library that has open reading frame (ORF) information regarding a plurality of peptides, wherein the nucleic acid library inherently includes at least 1,000,000 nucleic acid molecules encoding over 10,000 peptides and nucleic acid molecules of the nucleic acid library and comprise: a unique molecular identifier; a universal priming site for priming amplification and/or for sequencing of the library; at least three encoder barcodes including: one for wells or cells, a second for plate indexing and a third being a naturally ORF, such that: the library further optionally include PNA or locked nucleotides; and each encoder barcode necessarily provides an identifier tag associated with ORF codons such as an AUG translated to amino terminal methionine, a peptide component modified upon binding methionyl aminopeptidase. Such Mikkelsen library is purified with a solid support with nucleic acids necessarily spaced apart from one another on a surface. The foregoing reads on claims 178 (in part),179,180,182,183,184,186, 188,189,190,192,193,197,200, 202,203,204,205,206,207, 208,210,212,214.
The composition of Mikkelsen et al meets all of the structural limitations of the claimed library (see above) except for the product-by-process limitations set forth in claims claim 198 and 201 lines 13-17, (i.e., that "the nucleic acid library is obtained by transfer of an encoder barcode from a binding agent, which the encoder barcode identifies and is attached to, onto a single nucleic acid molecule upon binding of the binding agent to a component of one or more peptides of the plurality of peptides, and which transfer is performed for each encoder sequence barcode of the at least three different encoder barcodes") and thus would either anticipate or render obvious the claimed library. See MPEP § 2113, “‘[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.’ In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).” Here, claims 198 and 201 lines 13-17 are drawn to a polynucleotide library (i.e., a product), but are defined by various method steps that produce the library and, consequently, are deemed a product-by-process. However, the process limitations do not appear to provide any patentable weight to the claimed invention in accordance with MPEP § 2113, since the ordinary skilled artisan would expect the composition to be the same, no matter how it was generated.
Mikkelsen et al do not teach at least three different encoder barcodes each having a length from 4 to 30 nucleotides such that each constitutes an identifier tag for a binding agent that specifically binds to a component of a peptide and thereby comprises information regarding an amino acid sequence of the peptide like claims 178 and 201.
Yet, such as recited in claims 178 and 201, in an effort to prepare protein conjugates, Young et al teach throughout the document and especially the abstract, paragraph 0064 and figures 1,5 taken with paragraph 0109, incorporating unnatural amino acids (e.g. pApa, aka p-acetylphenylalanine) by expanding the standard genetic code with at least three different encoder barcodes (codons), each having a length from 4 to 5 nucleotides and each constitutes an identifier tag for a binding agent (e.g. ABT-510) that specifically binds to a component of a peptide and necessarily has information regarding the amino acid sequence in the peptide its transcript encodes.
It would have been prima facie obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention to have engineered proteins bearing unnatural amino acids with an expanded genetic code in the manner suggested by Young et al and perform clonal selection by high throughput RNA-seq as developed by Mikkelsen et al.
One of ordinary skill in the art would have been motivated to have engineered proteins bearing unnatural amino acids with an expanded genetic code in the manner suggested by Young et al and perform clonal selection by high throughput RNA-seq as developed by Mikkelsen et al in order to quickly select properly transformed cells: as interpreted in MPEP 2141 section III (C) the Supreme Court held under KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385, 1396 (2007) the use of a known technique (RNA-seq) to improve similar devices methods or products (synthesizing protein conjugates) in the same way is obvious.
One of ordinary skill in the art would have had a reasonable expectation of success in applying RNA-seq toward preparing protein conjugates in view of the compelling experimental results and detailed experimental protocols reported by Mikkelsen et al (e.g. paragraphs 0107-0125 and corresponding figures).
Regarding claim 211, the examiner submits during translation, peptides are indirectly attached to their encoding mRNA transcripts.
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Please note that the above rejection has been updated from the original version to more clearly address applicants’ newly amended and/or added claims and/or arguments.
Response to Arguments
The remarks accompanying the present response argue: (i) not all elements are taught; (ii) motivation is lacking.
Applicant’s arguments have been fully considered but they are not deemed persuasive for the following reasons.
Concerning (i) first more specifically pp 9-10 of the current remarks contends: Mikkelsen’s barcodes are used to track which well or cell a particular cDNA originated from and the UMI (unique molecular identifier) is used for sequencing, as opposed to claim 178 being drawn to three different encoder barcodes having a length 4 to 30 nucleotides, and that the encoder barcodes provide an identifier tag for a binding agent that specifically binds to a component a peptide and thereby comprises information regarding an amino acid sequence of the component of the one or more peptides.
First in response to applicant's argument that the references fail to show certain features of applicant’s invention, it is noted that the features upon which applicant relies (i.e., a UMI functioning as encoder barcode) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Second, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here the presently claimed barcodes are provided in Young et al which is discussed next.
Further concerning (i), p 11 of the remarks alleges the Young reference does not disclose at least three encoder barcodes (codons) in a single gene, rather one 4 base codon (pApa).
In this vein the following is noted. As interpreted in MPEP 2131 III, the courts have held “A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination.” Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)).
Here, Applicant’s attention is respectfully invited to paragraph 0109, as cited previously which states “Examples of four base codons include, e.g., AGGA, CUAG, UAGA, CCCU, and the like. Examples of five base codons include, e.g., AGGAC, CCCCU, CCCUC, CUAGA, CUACU, UAGG Four or more base codons can insert, e.g., one or multiple unnatural amino acids, into the same protein” (emphasis added) and in paragraphs 0086 and 0008 further detailing paragraph 0044, beyond pApa that binds with hydroxyamines, Young et al disclose unnatural amino acids including, for instance O-propargyl-L-tyrosine (that specifically binds with azides in a 1,3 dipolar cycloaddition “click” reaction), a biotin containing amino acid (that specifically binds streptavidin), etc.
As such, Young anticipates ‘at least three different encoder barcodes or each having a length of 4 nucleotides’ since the skilled artisan can immediately envisage a gene or transcript with at least AGGA, CUAG and UAGA four base barcodes encoding 3 unnatural amino acids, each specific for different binding agents.
Even further, in the pertinent section starting with paragraph spanning pp 11-12, the remarks allege when an unnatural codon is incorporated in DNA or RNA, it does not provide an identifier tag for ABT-510.
In response, as interpreted in MPEP 2123 I, the courts have held, “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art..”.Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)
Here, the examiner respectfully submits, in accordance with figure 5, it is shown that ABT-510 reacts with human serum albumin (HSA) containing pApa but not wild-type HSA. Working backward, the skilled artisan would appreciate the HSA unnatural codon confers this specificity change.
Finally concerning (ii), in the last paragraph at p 13, the remarks urge Mikkelsen’s high throughput RNA-Seq is useful when there is a need to determine unknown sequences in cells, whereas the DNA and RNA sequences are known in Young et al (from knowledge implied by the design).
In response, while the examiner does not disagree that the sequences are known, what is not known is whether sufficient transcript is generated tor translation. That is, for instance in accordance with Young paragraph 0118 and figure 4, promoters that are not induced by methanol may be advantageous and some are better than others. Accordingly, using high throughput RNA-Seq, the skilled artisan could beneficially quickly screen promoters for adequate transcription.
New Claim Rejection(s) – 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 178-180,182-184,186,188-190,192,193,197,198,200-208,210,211,212,214 and 215 are rejected under 35 U.S.C. 103 as being unpatentable over Mikkelsen et al (US PgPub 20160122753; of record) in view of Young et al (US PgPub 20100297693) and further in view of Wang et al (2014 Nat Chem. 6:393-403)
Mikkelsen et al in view of Young et al is relied upon as above.
Mikkelsen et al in view of Young et al do not teach encoder barcodes providing information regarding temporal binding of a binding agent to a single peptide of claim 215.
Using the same technology of Young et al, Wang et al teach throughout the document and especially figures 5 & 6a, simultaneous double calmodulin labeling at unnatural amino acids encoded with binding agents having similar kinetics (information regarding temporal order of a binding agent) like claim 215.
It would have been prima facie obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention to have engineered proteins bearing unnatural amino acids with an expanded genetic code in the manner suggested by Young et al and performed clonal selection by high throughput RNA-seq as developed by Mikkelsen et al for simultaneous double labeling in the manner of Wang et al.
One of ordinary skill in the art would have been motivated to have engineered proteins bearing unnatural amino acids with an expanded genetic code in the manner suggested by Young et al and performed clonal selection by high throughput RNA-seq as developed by Mikkelsen et al for simultaneous double labeling in the manner of Wang et al for the benefits of providing a modular route to install diverse pairs of probes into proteins at essentially any genetically controlled pair of sites in proteins at physiological temperature, pressure and pH as well as not generating toxic side products nor using toxic catalysts, all advantages noted by Wang et al in the Discussion.
One of ordinary skill in the art would have had a reasonable expectation of success in applying the modular double labeling approach of Wang et al toward preparing protein conjugates with clones screened with RNA-seq as in Mikkelsen et al in view of Young et al in view or the appreciable technological overlap between Young and Wang.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis 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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER M GROSS whose telephone number is (571)272-4446. The examiner can normally be reached M-F 10-6.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on (571)272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTOPHER M GROSS/
Primary Examiner, Art Unit 1684