DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This application is a continuation of application no. 15/816,263, filed 17 November 2017 (now abandoned), claiming priority to provisional application no. 62/423,574, filed 17 November 2016.
Claim Renumbering - Reminder
It is again noted that misnumbered claim “9” has been renumbered as claim 228, with incorrectly numbered claims “228-240” being renumbered as claims 229-241, respectively (see paragraph 2 of the Election/Restriction mailed 10 April 2026).
Election/Restrictions
Applicant’s election without traverse of Group I, and the species of a mixture that “encodes substantially all of a human genome” (as set forth in claim 222), in the reply filed on 10 June 2026 is acknowledged.
Claims 233-241 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 June 2026.
Claims 226 and 231 (as well as the alternative species of claim 222 directed to “methylated DNA”, and the alternative of claim 229 directed to nucleic acids comprising “a SapI restriction enzyme overhang”) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 June 2026.
Claims 221-225, 227-230, and 232 are under consideration herein (with claims 222 and 229 under consideration as directed to the elected species identified above).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 32 of the substitute specification filed 07 September 2023). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings (specifically in Figure 1C) are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Interpretation
With regard to the term “control”, it is noted that this term is discussed in paragraph 48 of the corresponding publication, which states that the “term “control” may refer to a control sample, process control, run control, positive control, negative control, validation sample, proficiency sample, reference material, standard, or analytical standard” (with further examples of such control types also being provided, which examples are consistent with the standard meaning of the term “control” as it is used in the art). Based on the totality of Applicant’s disclosure, while the term “control” is broad and encompasses a variety of alternative embodiments (as noted), the term has been interpreted as required that multiple nucleic acid mixtures as set forth in claim 221 must be present within a common, single sample/material/composition to be considered a “control” (i.e., the claims do not encompass, e.g., a kit including the recited two nucleic acid mixtures as set forth in claim 221 in separate vessel/tubes, as this would not reasonably be considered a single “control” usable as a reference/standard/sample/etc., based on the broadest reasonable interpretation of the term “control”).
With regard to the term “modified library” (which appears in claims 230 and 232), the specification states (at paragraph 76 of the published application):
The terms “library” and “sequencing library” herein refer to a collection or plurality of template molecules which share common sequences at their 5′ ends and common sequences at their 3′ ends.
Claims 230 and 232 have thus been interpreted as requiring DNA fragments having common sequences at their 5’ ends and 3’ ends. With further regard to claim 230, which is a “product-by-process” claim, as discussed in MPEP 2113, such claims “are not limited to the manipulations of the recited steps, only the structures implied by the steps”. With further regard to claim 232, the claimed method requires performing the recited steps/actions of (i)-(iii) (of “obtaining”, “amplifying’, and “digesting”) to obtain the “modified library”, and it is noted that the resulting “modified library” inherently meets the requirement of being a type of “control” (thus, the performance of the recited steps of claim 232 achieves the intended use of “generating a control”, despite the fact that those steps do not explicitly reference a “control”).
Claim Objections
Claim 230 (dependent from claim 221) and independent claim 232 are each objected to because of the following informalities: the claims employ the abbreviation “PCR” without first reciting the complete terminology. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)/second paragraph
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 223 and 229 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 223 is indefinite over the recitation of the limitation “wherein the ratio of the copy number of a nucleotide sequence that encodes a genotype of the first plurality of genotypes to the copy number of a nucleotide sequence that encodes a genotype of the second plurality of genotypes is 1:1000 to 1:1”, because it is unclear from this wording whether the recited further limitation applies to any one “genotype of the first plurality” and “genotype of the second plurality”, or to all such first and second genotypes. As there are multiple reasonable interpretations of the claim language that impart different boundaries on what is being claimed, further clarification is required.
Claim 229 is indefinite over the recitation of the language “wherein the nucleic acids of the control are encapsulated in a liposome, lipid, or a protein”, because it is unclear whether this language requires a control that includes the recited liposome, lipid, or protein (in addition to the nucleic acids), or whether only the environment/location of the “nucleic acids of the control” is being limited (such that there are multiple reasonable interpretations of the claim language that impart different boundaries on what is being claimed). Furthermore, to the extent that the claim is directed to the latter alternative, it is not clear how requiring the “nucleic acids of the control” to be present in a particular location/environment actually alters and further limits those nucleic acids. Further clarification is therefore needed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 221-225 and 227-230 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Heitzer et al (Genome Medicine 5:30 [2013]; cited herein), with further regard to claim 230, as evidenced by Illumina (TruSeq DNA Sample Prep HS Protocol, 22 pages [2012]; cited herein).
Heitzer et al teach whole genome sequencing of plasma DNA, reporting detection therein of tumor-associated aberrations, referring to this methodology as a “liquid biopsy” (see entire reference, particularly the Abstract). Heitzer et al teach that their methods comprise preparing shotgun libraries from their plasma DNA samples, and report that they eliminated a fragmentation step from their protocol because “all samples showed an enrichment of fragments in the range of 160 to 340 bp” (page 3, right column, “Plasma-Seq”, as well as the illustration in Figure 2); thus, Heitzer et al disclose that their analyzed samples - which are a type of “control” embraced by the claims (as discussed above under “Claim Interpretation”) - inherently include nucleic acids meeting the requirement of having “an average base pair (bp) length of about 50 bps to about 600 bps”. Heitzer et al report identifying multiple neoplasm-associated aberrations in at least some of their analyzed samples (see pages 8-9), and report estimates of tumor fraction in their analyzed prostate cancer samples as being over a range of around 31% to 54% (page 9, left column), making clear that their analyzed samples include both a “first mixture” of nucleic acids including a plurality of genotypes “associated with a neoplasm” and a “second mixture” of nucleic acids comprising genotypes “not associated with a disease”. Heitzer et al thus anticipate claim 221.
With further regard to dependent claim 222, given the origin of Heitzer et al’s samples (as well as their description of their analysis), it is an inherent property of those samples that the include a mixture that “encodes substantially all of a human genome”. Regarding dependent claim 223, based on the tumor fractions noted above, Heitzer et al disclose samples including copy number ratios embraced by the range set forth in the claims. Regarding dependent claim 224, it is an inherent property of the non-tumor DNA of Heitzer et al’s samples that it includes an alternative genotype as embraced by the claim; further, non-tumor DNA also meets the requirements of b) of claim 224. Regarding dependent claim 225, Heitzer et al teach rearrangements, copy number variations, mutations, etc. (see again, e.g., page 9). Regarding claim 227, this claim is also anticipated for the reasons discussed above (given Heitzer et al’s disclosure of multiple genotypes meeting the limitation “associated with a neoplasm”, and the nature of the samples disclosed). Regarding claim 228, the average range of “160 bp to 340 bp” taught by Heitzer et al meets the requirement of an average length of “about 100 bps to about 300 bps”. Regarding dependent claim 229, it is reiterated that the claim is indefinite, particularly with regard to how the fact that the claimed nucleic acids of the control are “encapsulated” actually further limits the claimed product; thus, claim 229 is rejected for the same reasons that apply to claim 221.
Regarding dependent claim 230, it is reiterated that this claim has been interpreted as requiring DNA fragments having common sequences at their 5’ ends and 3’ ends (see again the above Claim Interpretation). Heitzer et al disclose preparing libraries from their plasma DNA samples using a modification of the “TruSeq DNA LT Sample preparation Kit” protocol (see page 3, right column, “Plasma-Seq”). As evidenced by the TruSeq DNA Sample Prep protocol card, the protocol employed by Heitzer et al comprises, e.g., adenylation of 3’ ends (see pages 1 and 9), such that the methods taught by Heitzer et al inherently comprise preparation of a control meeting the requirements of claim 230.
Claim(s) 232 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Whitworth et al (Chapter 3 of “Mammalian Embryo Genomics”, OECD [2003]; cited herein).
Whitworth et al disclose preparing cDNA libraries by a method comprising obtaining DNA fragments (via reverse transcription), amplifying the DNA fragments, and digesting the amplified library with the restriction enzymes NotI and SalI (see entire reference, particularly pages 31-32). The method of Whitworth et al results in a “modified library” (resulting from the noted restriction digestion), which library inherently constitutes a type of “control” (see also the Claim Interpretation above). Whitworth et al thus anticipate claim 232.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 229 is rejected under 35 U.S.C. 103 as being unpatentable over Heitzer et al (Genome Medicine 5:30 [2013]; cited herein) in view of Abdueva (US 2014/0371078 A1 [18 Dec 2014]; cited in IDS) and Berg et al (Journal of Microbiological Methods 55:303-309 [2003]; cited in IDS).
It is noted that claim 229 is also rejected under 35 USC 102(a)(1) for the reasons set forth above; this rejection applies to the claim to the extent that it may require a control that is a liposome in which the first and second nucleic acid mixtures as specified in claim 221 are encapsulated.
Heitzer et al teach whole genome sequencing of plasma DNA, reporting detection therein of tumor-associated aberrations, referring to this methodology as a “liquid biopsy” (see entire reference, particularly the Abstract). Heitzer et al teach that their methods comprise preparing shotgun libraries from their plasma DNA samples, and report that they eliminated a fragmentation step from their protocol because “all samples showed an enrichment of fragments in the range of 160 to 340 bp” (page 3, right column, “Plasma-Seq”, as well as the illustration in Figure 2); thus, Heitzer et al disclose that their analyzed samples - which are a type of “control” embraced by the claims (as discussed above under “Claim Interpretation”) - inherently include nucleic acids meeting the requirement of having “an average base pair (bp) length of about 50 bps to about 600 bps”. Heitzer et al report identifying multiple neoplasm-associated aberrations in at least some of their analyzed samples (see pages 8-9), and report estimates of tumor fraction in their analyzed prostate cancer samples as being over a range of around 31% to 54% (page 9, left column), making clear that their analyzed samples include both a “first mixture” of nucleic acids including a plurality of genotypes “associated with a neoplasm” and a “second mixture” of nucleic acids comprising genotypes “not associated with a disease”. Heitzer et al thus teach a “control” meeting all limitation of independent claim 221, from which instant claim 229 depends.
Heitzer et al do not teach a control comprising a liposome in which nucleic acid mixtures as required by claim 221 are “encapsulated”.
Abdueva discloses nucleic acid sequencing-based methods for determining copy number variations, emphasizing the application of their methods to fetal gender determination and aneuploidy detection, but also teaching that their methods may be employed in detecting disease associated variations, including cancer associated copy number variations, i.e., variations of the type taught by Heitzer et al (see entire reference, particularly, e.g., paragraphs 8, 48, 71, 120, 186, 232, 262, 267, 271-276).
For use in their methods, Abdueva disclose and describe the preparation of various types of in process positive controls (IPCs) (see paragraphs 259-267), including IPCs employed “to track samples through the sequencing process”, which IPCs may provide “a qualitative positive sequence dose value” for the variation or variations of interest, in order to “provide proper interpretation, and to ensure the dependability and accuracy of the data” (paragraph 263). Abdueva disclose various ways of preparing DNA (including cfDNA) for use in their controls (see, e.g., paragraphs 265-266), stating, e.g., that an IPC “can be created using cfDNA obtained from a mother known to carry a fetus with a known chromosomal aneuploidy” (paragraph 266), as well as by mixing cellular DNA from two subjects representing different genomes (one with an aberration, one without) (paragraph 265). Abdueva also teach that “a preferred sample for analysis via their methods includes “a plasma sample from a cancer patient” (paragraph 186) – i.e., samples analogous to those of Heitzer et al - providing further motivation to prepare such controls/markers for use in cancer diagnostics. Abueva thus (like Heitzer et al) teach and suggest controls including nucleic acids “encoding substantially all of a human genome” (as required by the elected species), which controls also represent chromosomal aberrations (which may be cancer associated; see paragraph 267 of Abdueva in particular).
With regard to the claim limitation “the nucleic acids of the control are encapsulated by a liposome, lipid, or protein”, Abdueva further teaches that
various methods may be used to facilitate incorporation of their markers/controls into samples to be, or in the process of being, tested, with one such preferred method being the use of “cell-delivery carriers including pH-sensitive and cationic liposomes” to allow for delivery of markers into cells of a sample being tested (see paragraph 251). Abdueva thus suggests the use of liposomes comprising control nucleic acids as preferred types of controls; however, Abdueva does not explicitly teach the claim limitation that the control nucleic acids must be “encapsulated in” a liposome.
Berg et al teach the use of liposomes containing target nucleic acids as “cell-mimicking vehicles” for use as internal controls in amplification-based DNA detection assays, noting that such controls may be introduced “directly into the crude biological specimens”, and that they were found to be versatile and “applicable for whole process quality control” (see entire reference, particularly the Abstract). Berg et al teach incorporating control nucleic acids into liposomes via a freeze/thawing procedure, with the liposomes being loaded with “relatively few DNA molecules” and adjusted in size so as to prepare “synthetic cell-mimicking particles” (see page 304, right column-page 305, left column). Berg et al state that their liposome controls were tested for their ability to serve “as a tool for whole process quality assurance of nucleic acid amplification-based analysis” (page 307, right column), noting that the “use of naked internal control gives only a partial quality assurance of the nucleic acid –based amplification assays” (page308, left column), while “the nonviable cell-mimicking liposome/internal control particles seem to be versatile and applicable for whole process quality control of nucleic acid amplification-based assays for detection of various pathogens and cells” (page 309, left column).
In view of the teachings of Abdueva and Berg et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the samples of Heitzer et al by preparing liposomes encapsulating the nucleic acids of those samples, and thereby to have prepared a control meeting the requirements of claim 229. An ordinary artisan would have been motivated to have made such a modification for the benefit of preparing a composition that would function successfully in the delivery of the marker/control nucleic acids of Heitzer et al into a sample intended for testing or in the process of being tested, as taught by Abdueva, and for the further benefit – as taught by Berg et al – of employing a control that mimics a natural target of interest (as compared to a naked nucleic acid control) and which allows for whole process quality control (it is also particularly noted that the instant claims embrace any product meeting the requirements set forth in the claims, without requiring that those products be employed in a particular way [as would be the case if the claims were directed to methods specifying a particularly use]). Further, given Berg et al’s teachings that their liposome controls are suitable for use in amplification-based assays, as well as Abdueva’s explicit disclosure of the use of liposome controls in their methods, and of the addition of controls at any point in their methods prior to sequencing, an ordinary artisan would have had a reasonable expectation of success in preparing and using such controls in, e.g., a diagnostic test and a validation thereof.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
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.
Claims 221-225 and 227-230 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon/law of nature without significantly more.
Independent claim 221 recites a “control” that comprises first and second mixtures of nucleic acids, with the “first mixture” comprising a plurality of nucleotide sequences encoding genotypes associated with a neoplasm, and the “second mixture” comprising a plurality of nucleotide sequences encoding genotypes “no associated with a disease”; the nucleic acids of the first or second mixture “have an average base pair (bp) length of about 50 bps to about 600 bps” (see text of claim 221). As discussed above under “Claim Interpretation”, the term “control” as employed in the application embraces things such as “control samples”, such that the claims encompass, e.g., biological samples employed as controls, so long as those samples otherwise meet the requirements of the claims. As discussed above in the rejection of these claims under 35 USC 102 over Heitzer et al (Genome Medicine 5:30 [2013]; cited herein), the claims embrace “controls” such as naturally occurring plasma DNA samples. Such samples comprise nucleic acid fragments as they exist in nature, lacking any features that render them “markedly different” from naturally occurring nucleic acids. These claims thus recite and are directed to a judicial exception; while it is noted that the claims potentially also embrace “controls” that might be considered markedly different from naturally occurring nucleic acids, as stated in MPEP 2106.03(II): “A claim whose BRI covers both statutory and non-statutory embodiments embraces subject matter that is not eligible for patent protection and therefore is directed to non-statutory subject matter”.
This judicial exception (JE) is not integrated into a practical application because there are no additional elements required by the claims that might potentially integrate the claimed products into a practical application. Further, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because (again) nothing more is present in the claims that amounts to “more” than the JE.
Regarding dependent claim 222, the recitation of a first or second mixture of nucleic acids that “encodes substantially all of a human genome” simply requires a further, more particularly type of natural product; nothing “markedly different” is required, nor does this further requirement amount to a practical application or something “significantly more” than a JE. With further regard to dependent claim 223, the recitation in the claim of a ratio that embraces naturally occurring ratios (as evidenced by, e.g., Heitzer et al) does not render the claimed products markedly different from naturally nucleic acids, and does not add anything amounting to a practical application, or something “significantly more” than a JE. Dependent claims 224-225 and 227-228 similarly recite features that also characterize naturally occurring nucleic acid samples, such that this same analysis applies to those claims. Dependent claim 229 specifies a location of the “nucleic acids of the control” within a liposome, lipid, or protein, but does not clearly require any type of practical application or additional features amounting to “more” than a JE; further, the location of the claimed nucleic acids in a specific environment does not clearly require any kind of markedly different characteristics relative to these molecules as they occur in nature. Finally, while the products of claim 230 must include nucleic acids that share common 5’ and 3’ ends, one of skill in the art would recognize that naturally occurring samples/ compositions embraced by the claims would necessarily include at least some nucleic acids fragments sharing these features, such that the claim as written does not require markedly different characteristics, or a requirement for a practical application or something “significantly more”.
Accordingly, none of claims 221-225 and 227-230 as presently written is directed to patently eligible subject matter.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 221-225 and 227-230 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 79, 95-96, 100, 103, 107, 110, 141-142, 149, 159-160, and 210 of copending Application No. 17/553,299 (published as US20220178939 [cited herein]). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant claims and the ‘299 claims are each directed to controls comprising first and second mixtures of nucleic acids. While the ‘299 claims recite a requirement for “at least three nucleotide sequences” encoding at least 3 genotypes associated with “at least 3 different types of neoplasms”, this is a species of control that is embraced by the broader language of the instant claims. Further, while ‘299 independent claim 79 does not recite average base pair lengths as is the case with instant independent claim 221, ‘299 claim 110 sets forth median lengths that are embraced by the language of the instant claims, such that the ‘299 claims suggest the products of the instant claims. The ‘299 dependent claims also set forth preferred embodiments suggesting the instant elected species of the inclusion of “substantially all of a human genome” (see, e.g., ‘299 claims 95-96), encapsulation in liposomes (see, e.g., ‘299 independent claim 79), and copy number ratios (referenced in the ‘299 claims as percentages, see, e.g., ‘299 claims 103 and 210). Accordingly, the ‘299 claims suggest products as set forth in the instant claims, and the instant claims are therefore not patentably distinct from the ‘299 claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 221-225 and 227-230 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-47, 71-81, and 87-109 of copending Application No. 19/709,390 [unpublished]), and claim 232 is rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 204-220 of the ‘390 application. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Regarding the products of instant claims 221-225 and 227-230, the instant claims and ‘390 claims 1-47, 71-81, and 87-109 are each directed to nucleic-acid containing controls/reference materials comprising first and second mixtures of nucleic acids (with the ‘390 claims reciting second mixtures in dependent claims, e.g., claims 3-4, 18-19, 38-39). The ‘390 claims further recite length limitations generally corresponding to those of the instant claims (see ‘390 independent claims 1, 16, 31), and embrace neoplastic genotypes (as set forth in, e.g., dependent claims 6 and 21). The ‘390 claims further embrace preferred genotype ratios as are set forth in the instant claims (see, e.g., ‘390 claims 5 and 20), and also embrace products corresponding to the elected species requiring a second mixture of nucleic acids “encoding substantially all of” a human genome (see, e.g., 390 claim 4 and 87-88). The instant claims are thus obvious over, and not patentably distinct from, ‘390 claims 1-47, 71-81, and 87-109.
Regarding methods as set forth in instant claim 232, while this claim is not identical to independent claims 204 of the ‘790 application (from which claims 205-220 depend), ‘790 claim 204 recites a more particular type of DNA fragments that are “obtained”, amplified by PCR, and digested with a restriction enzyme (inherently resulting in a “control” as set forth in the instant claim). ‘790 claims 204-220 are thus directed to species of an invention encompassed by instant claim 232, and anticipate that claim (such that instant claim 232 is not patentably distinct from ‘790 claims 204-220).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 221-225 and 227-230 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 206-224 of copending Application No. 19/709,507 (unpublished). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant claims are directed to controls comprising first and second mixtures of nucleic acids, while the ‘507 claims recite methods employing controls of this type.
While the controls of the ‘507 claims require “at least 3 nucleotide sequences” encoding at least 3 genotypes associated with “at least 3 different types of neoplasms”, this is a species of control that is embraced by the broader language of the instant claims. Further, while ‘507 independent claim 206 and 223-224 do not recite average base pair lengths as is the case with instant independent claim 221, ‘507 claim 215 recites median lengths encompassed by the language of the instant claims, such that these lengths are suggested by the ‘507 claims. The ‘507 dependent claims also set forth preferred embodiments suggesting the instant elected species of the inclusion of “substantially all of a human genome” (see, e.g., ‘507 claims 209-210 and 221), encapsulation in liposomes (see, e.g., ‘507 independent claim 206 and 223-224), and copy number ratios (referenced in the ‘507 claims as percentages, see, e.g., ‘507 claim 214). Accordingly, the ‘507 claims, by suggesting the use of controls encompassed by the language of the instant claims, render obvious those types of controls (such that the instant claims are not patentably distinct from the ‘507 claims).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
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