DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment filed on 05/18/2026 has been entered.
Claims 1, 3-5, 8, 9, 12, 14, and 15 were amended in the claim set filed on 05/18/2026.
Applicant’s election of Group I, claims 1-18, drawn to a method of determining if a companion animal is likely to have cancer in the reply filed on 10/30/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 16-24 are withdrawn drawn to a nonelected Group II and non-elected species.
Claims 1-15 in the claim set filed on 05/18/2026 are currently under examination.
Response to the Arguments
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-11 under 35 U.S.C. 112 have been fully considered and are persuasive. The 35 U.S.C. 112 rejections documented in the previously mailed non-final have been withdrawn in light of applicants claim amendments and arguments on Pg. 6. However, as necessitated by amendment, new grounds of rejection are made below in the 35 U.S.C. 112 section of this office action on Pg. 4-5.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-15 under 35 U.S.C. 101 have been fully considered but are not persuasive. Applicant' s argument on Pg. 7, states that “Applicant respectfully disagrees with the Examiner's assertions that these active steps in claim 1 and 12 are routine and conventional.” The 35 U.S.C. 101 rejections documented in the previously mailed non-final rejections are maintained and revised in light of applicants claim amendments and arguments on Pg. 16-18. Revised rejections for claims 1-15 are made as documented below in the 35 U.S.C. 101 rejection in this office action on Pg. 5-11.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-15 under 35 U.S.C. 103 have been fully considered but are not persuasive. Applicant' s argument on Pg. 9, states that “Buis does not appear to teach or suggest using a sequence specific primer that is derived from repeat elements present throughout the genome of the companion animal to obtain copies of the repeat elements and unique genomic sequences which are adjacent to each repeat element, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the companion animal, such as a canine animal. Therefore, it fails to teach or suggest all of the claimed limitations, when taken alone in when combined with the disclosure in Mounts.” As necessitated by amendment, the 35 U.S.C. 103 rejections of claim(s) 1-15 documented in the previously mailed non-final have been maintained and revised in light of applicants claim amendments. Revised rejections are made as documented below in the 35 U.S.C. 103 rejection in this office action on Pg. 10-15.
The new grounds of rejections and maintained and revised rejections for claims 1-15 are documented below in this Final Office Action are necessitated by claim amendments filed on 04/13/2026.
Priority
This application is a CON of PCT Application No. PCT/US2020/065337, filed on 12/16/2020, which claims benefit of U.S. Provisional Application No. 62/949,920, filed on 12/18/2019. The priority date of claim set filed on 06/09/2022, is determined to be 12/18/2019.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 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.
The term “unique” in “unique genomic sequence” in claims 1, 3 and 12 is a relative term which renders the claim indefinite. The term “unique” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Specification teaches: Because the nucleotide sequences adjacent to each SINE motif sequence are generally unique in the genome. (Para. 28) It is unclear as to what the measurement is needed to be considered unique. Claims 2-11 depend on claim 1 and claims 13-15 depend on claim 12.
Claims 14-15 are indefinite over “the unique nucleotide sequences adjacent to each SINE sequence” (ln 2) as the unique nucleotide sequences is not recited in claim 12 . It is unclear whether the unique nucleotide sequences are the same sequences of claim 12 (ln 6-7). Claim 12 is drawn to “unique genomic sequences adjacent to each SINE sequence” (ln 6-7), however the specification also recites “unique nucleotide barcodes (often called unique molecular identifiers)” (Para. 30) and “a unique multiplex code” (Para. 41).
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 1-15 remain rejected under 35 U.S.C. 101 because the claimed invention is directed towards abstract ideas(mental processes) of determining, law of nature (natural correlation) of cancer to number and distribution of copies of genomic sequences and routine and conventional step of amplifying and determining the number and distribution of the copies, without significantly more. The claim(s) recite(s) abstract ideas, Law of nature and routine and conventional methods. This judicial exception is not integrated into a practical application because no additional elements integrate the judicial exceptions into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are considered significantly more than the judicial exceptions.
Claim analysis
The instant claim 1 is directed towards: A method of determining the number of copies of amplified regions in a circulating cell free DNA (cfDNA) sample and their distribution in the genome of if a companion animal suspected of having cancer, comprising isolating cfDNA from a biological sample taken from a companion animal suspected of having cancer; amplifying the cfDNA using a sequence specific primer that is derived from short interspersed nuclear element (SINE) sequences present throughout the genome of the companion animal to obtain copies of the SINE sequence and unique genomic sequences adjacent to each SINE sequence; determining the number and distribution of the copies of amplified regions in the cfDNA, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the companion animal; and determining whether the companion animal is likely to have cancer based on the number and distribution of copies of the amplified regions, including the unique adjacent genomic sequences in the companion animal suspected of having cancer as compared to the number of copies of the amplified region in one or more healthy animals, wherein a difference indicates that the companion animal is highly likely to have cancer.
The “isolating cfDNA from a biological sample taken from a companion animal”, “determining the number and distribution of the copies of amplified regions in the cfDNA”, and determining whether the companion animal is likely to have cancer based on the number and distribution of copies of the amplified regions, including the unique adjacent genomic sequences in the companion animal suspected of having cancer as compared to the number of copies of the amplified region in one or more healthy animals are considered abstract ideas (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work and is considered to be active steps requiring the analysis of a sample.
The “companion animal is likely to have cancer based on the number and distribution of copies of the amplified regions, including the unique adjacent genomic sequences in the companion animal suspected of having cancer as compared to the number of copies of the amplified region in one or more healthy animals, wherein a difference indicates that the companion animal is highly likely to have cancer” is a Law of nature (natural correlation) related to the number and distribution of copies of the amplified regions (SINE and unique adjacent genomic sequences) to a companion animal likely to have cancer.
The “amplifying the cfDNA using a sequence specific primer that is derived from short interspersed nuclear element (SINE) sequences is considered to be active steps requiring the analysis of a sample. The active step is routine and conventional as demonstrated by the 35 USC § 103 rejections stated below.
Dependent claims set forth further limitations about the companion animal, sequence specific primer, sample, determination of the number and distribution of copies of amplified regions, and amplification of SINE sequence.
The instant claim 12 is directed towards: A method of identifying the number and distribution of short interspersed nuclear element (SINE) sequences in canine genomic sequences, comprising: isolating circulating cell free DNA (cfDNA) in from a biological sample taken from a canine animal, wherein the sample contains canine genomic sequences; amplifying SINE sequences and unique genomic sequences adjacent to each SINE sequence from the canine genomic sequences to determine the number and distribution of SINE sequences in the canine genomic sequences, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the canine animal; and determining whether the companion animal is likely to have cancer based on the number and distribution of the SINE sequences as compared to the number and distribution of the SINE sequences in a healthy animal.
The “isolating circulating cell free DNA (cfDNA) in from a biological sample taken from a canine animal”, “determine the number and distribution of SINE sequences in the canine genomic sequences, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the canine animal; and determining whether the companion animal is likely to have cancer based on the number and distribution of the SINE sequences as compared to the number and distribution of the SINE sequences in a healthy animal” are considered abstract ideas (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work and is considered to be active steps requiring the analysis of a sample.
The “amplifying SINE sequences and unique genomic sequences adjacent to each SINE sequence from the canine genomic sequences” is considered to be an active step requiring the analysis of a sample. The active step is routine and conventional as demonstrated by the 35 USC § 103 rejections stated below.
The “companion animal is likely to have cancer based on the number and distribution of the SINE sequences as compared to the number and distribution of the SINE sequences in a healthy animal” is a Law of nature (natural correlation) related to the number and distribution of the SINE sequences to a companion animal likely to have cancer.
Dependent claims set forth further limitations about the sequence specific primer, sample and amplification of SINE sequence.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? Yes, a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract ideas and law of nature.
With regard to claim 1, the claim recites “A method of determining the number of copies of amplified regions in a circulating cell free DNA (cfDNA) sample and their distribution in the genome of if a companion animal suspected of having cancer, comprising isolating cfDNA from a biological sample taken from a companion animal suspected of having cancer; amplifying the cfDNA using a sequence specific primer that is derived from short interspersed nuclear element (SINE) sequences present throughout the genome of the companion animal to obtain copies of the SINE sequence and unique genomic sequences adjacent to each SINE sequence; determining the number and distribution of the copies of amplified regions in the cfDNA, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the companion animal; and determining whether the companion animal is likely to have cancer based on the number and distribution of copies of the amplified regions, including the unique adjacent genomic sequences in the companion animal suspected of having cancer as compared to the number of copies of the amplified region in one or more healthy animals, wherein a difference indicates that the companion animal is highly likely to have cancer.” The “isolating cfDNA from a biological sample taken from a companion animal”, “determining the number and distribution of the copies of amplified regions in the cfDNA”, and “determining whether the companion animal is likely to have cancer based on the number and distribution of copies of the amplified regions, including the unique adjacent genomic sequences in the companion animal suspected of having cancer as compared to the number of copies of the amplified region in one or more healthy animals” are considered abstract ideas (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work and is considered to be active steps requiring the analysis of a sample. The “companion animal is likely to have cancer based on the number and distribution of copies of the amplified regions, including the unique adjacent genomic sequences in the companion animal suspected of having cancer as compared to the number of copies of the amplified region in one or more healthy animals, wherein a difference indicates that the companion animal is highly likely to have cancer” is a Law of nature (natural correlation) related to the number and distribution of copies of the amplified regions (SINE and unique adjacent genomic sequences) to a companion animal likely to have cancer.
With regard to claim 12, the claim recites “A method of identifying the number and distribution of short interspersed nuclear element (SINE) sequences in canine genomic sequences, comprising: isolating circulating cell free DNA (cfDNA) in from a biological sample taken from a canine animal, wherein the sample contains canine genomic sequences; amplifying SINE sequences and unique genomic sequences adjacent to each SINE sequence from the canine genomic sequences to determine the number and distribution of SINE sequences in the canine genomic sequences, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the canine animal; and determining whether the companion animal is likely to have cancer based on the number and distribution of the SINE sequences as compared to the number and distribution of the SINE sequences in a healthy animal.” The “isolating circulating cell free DNA (cfDNA)”, “unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome and determining whether the companion animal is likely to have cancer based on the number and distribution of the SINE sequences as compared to the number and distribution of the SINE sequences in a healthy animal is considered to be an abstract idea (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work and is considered to be active steps requiring the analysis of a sample.
The “companion animal is likely to have cancer based on the number and distribution of the SINE sequences as compared to the number and distribution of the SINE sequences in a healthy animal” is a Law of nature (natural correlation) related to the number and distribution of the SINE sequences to a companion animal likely to have cancer.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? No, there are no additional steps that integrate the claims into a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, there are no additional elements that are significantly more than the judicial exceptions.
Regarding claims 1 and 12, the claim requires the routine and conventional active steps of amplifying the cfDNA using a sequence specific primer and determining the number and distribution of the copies of amplified regions in the cfDNA similar to that of Buis et al. (“Buis”; Patent App. Pub. US 20190309352 A1, Oct. 10, 2019, filed on Nov. 16, 2017).
Buis discloses “The invention provides methods for determining whether a subject is predisposed to the disease or condition, or for diagnosing a disease or condition, or for detecting the state of a disease or condition, by detecting nucleic acid fragment size patterns, copy number variations, mutational landscape, genomic instability, methylation status, and combinations thereof in a subject. The invention further provides methods for selecting nucleic acid molecules for use in the methods of the invention.” (Abstract).Thus, the claim does not provide additional steps which are significantly more.
Dependent claims require limitations about the companion animal, sequence specific primer, sample, determination of the number and distribution of copies of amplified regions, and/or amplification of SINE sequence. which are all routine and conventional based on Buis et al. (“Buis”; Patent App. Pub. US 20190309352 A1, Oct. 10, 2019, filed on Nov. 16, 2017) in view of Mounts et al. (“Mounts”; Patent App. Pub. US 20070009899 A1, Jan. 11, 2007).
Claim Rejections - 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.
Claim(s) 1-3, 6-7 and 10-11 remain rejected under 35 U.S.C. 103 as being unpatentable over Buis et al. (“Buis”; Patent App. Pub. US 20190309352 A1, Oct. 10, 2019, filed on Nov. 16, 2017).
Buis discloses “The invention provides methods for determining whether a subject is predisposed to the disease or condition, or for diagnosing a disease or condition, or for detecting the state of a disease or condition, by detecting nucleic acid fragment size patterns, copy number variations, mutational landscape, genomic instability, methylation status, and combinations thereof in a subject. The invention further provides methods for selecting nucleic acid molecules for use in the methods of the invention.” (Abstract).
Regarding claim 1, Buis teaches “The methods and compositions disclosed herein may be useful for the detection, diagnosis, or prognosis of a wide range of diseases and conditions including, but not limited to, cancer” (Para. 86). Buis teaches a method comprising “A method for determining the nucleotide sequence of one or more target nucleic acids in a subject” (Para. 7). Buis teaches a method comprising “The terms “subject” and “patient”, as used herein, refer to any animal, such as a dog … and particularly a mammal” (Para. 116). Thus, Buis suggests a method of determining if a companion animal is likely to have cancer.
Buis teaches a method comprising “obtaining a nucleic acid sample isolated from a subject” (Para. 8) and “the nucleic acid molecule may be cell-free DNA (cfDNA)” (Para. 117). Buis teaches a method comprising “an individual suspected of having a disease or condition” (Para. 141). Thus, Buis suggests isolating cfDNA from a biological sample taken from a companion animal suspected of having cancer.
Buis teaches a method comprising “ c) hybridizing an anchor primer ... and hybridizing a genome-informed primer, which is substantially complementary to a repeat sequence in the nucleic acid, to produce a plurality of replicons, wherein the anchor sequence and the repeat sequence flank a gap region in the plurality of target nucleic acid sequences of interest; d) … amplicons that are amplified from the replicons in step c)” (Para. 10-11). Buis also teaches a method wherein “a genome-informed primer, which is substantially complementary to a repeat sequence in the nucleic acid” and “wherein the repeat sequence is selected from the group consisting of Alu repeats” (Para. 12). “Alu repeats” read on SINE sequences and one of the most common SINE sequences in mammals. Thus, Buis suggests a method comprising amplifying the cfDNA using a sequence specific primer that is derived from short interspersed nuclear element (SINE) sequences present throughout the genome of the companion animal to obtain copies of the SINE sequence and unique genomic sequences adjacent to each SINE sequence.
Buis teaches a method comprising “further comprising determining the number of the unique amplicons sequenced at step d); determining a read density based at least in part on the number of unique amplicon sequences” (Para. 12). Furthermore, Buis teaches a method comprising “one can align the DNA to the genome using standard or custom methods” (Para. 303). Thus, Buis suggests a method comprising determining the number and distribution of the copies of amplified regions in the cfDNA, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the companion animal.
Buis teaches a method comprising “detecting copy number variation by comparing the read density to a plurality of reference read densities that are computed based on reference nucleic acid samples isolated from reference subjects” (Para.12). Buis also teaches a method comprising “wherein reference value is from one or more cancer-free subjects” (Para. 16) and “the sample comprises at least one nucleic acid sequence whose genome is suspected of having undergone variation… used to detect a disease or condition, or detect the state of a disease or condition, or determine whether a subject has a predisposition to a disease or condition, in samples from any mammal” (Para. 118). Buis teaches a method comprising “b) calculating a first value of a first parameter based on the amounts of nucleic acids at the plurality of sizes, the first parameter providing a statistical measure of a size profile of nucleic acids in the sample; c) comparing the first value to a reference value” (Para. 14-15). Thus, Buis suggests a method comprising determining whether the companion animal is likely to have cancer based on the number and distribution of copies of the amplified regions, including the unique adjacent genomic sequences in the companion animal suspected of having cancer as compared to the number of copies of the amplified region in one or more healthy animals, wherein a difference indicates that the companion animal is highly likely to have cancer.
Therefore, the invention as recited in claim 1 is prima facie obvious over the prior art Buis et al. One of ordinary skill in the art would have had a reasonable expectation of success given these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and would have yielded the predictable outcome according to the limitations of claim 1 in view of the teachings of Buis et al.. It would have been obvious to determine the number of copies of amplified regions in a circulating cell free DNA (cfDNA) sample and their distribution in the genome of a companion animal suspected of having cancer according to the limitations of the instant application claims 1 based on Buis et al. (Patent App. Pub. No. US 20190309352 A1).
The teachings of Buis are documented above in the rejection of claims 1 under 35 U.S.C. 103. Claim 2-3, 6 and 10 depend on claim 1. Claim 7 depends on claim 6, which depends on claim 1. Claim 11 depends on claim 10, which depends on claim 1.
Regarding claim 2, Buis teaches a method wherein “The terms “subject” and “patient”, as used herein, refer to any animal, such as a dog” (Para. 116). Thus, Buis suggests a method wherein the companion animal is a dog.
Regarding claim 3, Buis teaches a method wherein “a genome-informed primer, which is substantially complementary to a repeat sequence in the nucleic acid” and “wherein the repeat sequence is selected from the group consisting of Alu repeats” (Para. 12).”Alu repeats” read on SINE sequences and one of the most common SINE sequences in mammals.
Regarding claim 6, Buis teaches a method wherein “sample is a blood sample” (Para. 118).
Regarding claim 7, Buis teaches a method wherein “circulating tumor DNA (ctDNA) in blood” (Para. 140).
Regarding claim 10, Buis teaches a method wherein “multiple layers of unique molecular tags and/or barcodes can be used within the methods to identify specific primer species” (Para. 140).
Regarding claim 11, Buis teaches a method wherein “The term “MIP,” as used herein, refers to a molecular inversion probe (also known as a circular capture probe). As used herein, the terms “primer”, “probe”, or “capture probe” also may refer to a MIP” and “the polynucleotide linker (or the backbone linker) in the MIPs are universal” (Para. 119).
Therefore, the invention as recited in claims 1-3, 6-7 and 10-11 are prima facie obvious over the prior art Buis et al. One of ordinary skill in the art would have had a reasonable expectation of success given these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and would have yielded the predictable outcome according to the limitations of claim 1-3, 6-7 and 10-11 in view of the teachings of Buis et al.. It would have been obvious to determine if a companion animal is likely to have cancer according to the limitations of the instant application claims 1-3, 6-7 and 10-11 based on Buis et al. (Patent App. Pub. No. US 20190309352 A1).
Response to Arguments
Applicant's arguments filed 05/18/2026 (Pg. 8-10) with respect to claims 1-3, 6-7 and 10-11 have been fully considered but they are not persuasive. To clarify some instances argued in the response filed 05/18/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “Buis does not appear to teach or suggest using a sequence specific primer that is derived from repeat elements present throughout the genome of the companion animal to obtain copies of the repeat elements and unique genomic sequences which are adjacent to each repeat element, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the companion animal, such as a canine animal. Therefore, it fails to teach or suggest all of the claimed limitations, when taken alone in when combined with the disclosure in Mounts.” (Pg. 9)
Response: Applicant’s arguments have been fully considered and found unpersuasive because as stated in the revised 35 USC 103 rejection above on Pg. 12-13, “Buis teaches “The methods and compositions disclosed herein may be useful for the detection, diagnosis, or prognosis of a wide range of diseases and conditions including, but not limited to, cancer” (Para. 86). Buis teaches a method comprising “A method for determining the nucleotide sequence of one or more target nucleic acids in a subject” (Para. 7). Buis teaches a method comprising “The terms “subject” and “patient”, as used herein, refer to any animal, such as a dog … and particularly a mammal” (Para. 116). Thus, Buis suggests a method of determining if a companion animal is likely to have cancer.
Buis teaches a method comprising “obtaining a nucleic acid sample isolated from a subject” (Para. 8) and “the nucleic acid molecule may be cell-free DNA (cfDNA)” (Para. 117). Buis teaches a method comprising “an individual suspected of having a disease or condition” (Para. 141). Thus, Buis suggests isolating cfDNA from a biological sample taken from a companion animal suspected of having cancer.
Buis teaches a method comprising “c) hybridizing an anchor primer ... and hybridizing a genome-informed primer, which is substantially complementary to a repeat sequence in the nucleic acid, to produce a plurality of replicons, wherein the anchor sequence and the repeat sequence flank a gap region in the plurality of target nucleic acid sequences of interest; d) … amplicons that are amplified from the replicons in step c)” (Para. 10-11). Buis also teaches a method wherein “a genome-informed primer, which is substantially complementary to a repeat sequence in the nucleic acid” and “wherein the repeat sequence is selected from the group consisting of Alu repeats” (Para. 12). “Alu repeats” read on SINE sequences and one of the most common SINE sequences in mammals. Thus, Buis suggests a method comprising amplifying the cfDNA using a sequence specific primer that is derived from short interspersed nuclear element (SINE) sequences present throughout the genome of the companion animal to obtain copies of the SINE sequence and unique genomic sequences adjacent to each SINE sequence.
Buis teaches a method comprising “further comprising determining the number of the unique amplicons sequenced at step d); determining a read density based at least in part on the number of unique amplicon sequences” (Para. 12). Furthermore, Buis teaches a method comprising “one can align the DNA to the genome using standard or custom methods” (Para. 303). Thus, Buis suggests a method comprising determining the number and distribution of the copies of amplified regions in the cfDNA, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the companion animal.” One of skill in the art would understand that the adjacent sequence to a sequence complementary to specific primer region would be amplified depending on the sequence length of the repeat sequence.
Thus, Buis does suggest a method comprising using a sequence specific primer that is derived from repeat elements present throughout the genome of the companion animal to obtain copies of the repeat elements and unique genomic sequences which are adjacent to each repeat element, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the companion animal, such as a canine animal.
Applicants’ argument: “the examples mostly appear to be prophetic examples which, in the absence of the teachings of the instant application, would not have provided the skilled person with a reasonable expectation that the claimed invention would work, which is a requirement for a prima facie case of obviousness under 35 U.S.C.§103. ”(Pg. 9).
Response: In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). These claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome according to the limitations of claims 1-3, 6-7 and 10-11.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Buis et al. (“Buis”; Patent App. Pub. US 20190309352 A1, Oct. 10, 2019, filed on Nov. 16, 2017).
Regarding claim 12, Buis teaches “a method for determining the nucleotide sequence of one or more target nucleic acids in a subject” (Para. 7). Buis teaches methods comprising “a method of determining whether a subject has a predisposition to a disease or condition that is associated with ... CNV [copy number variation] status ... Particular diseases and conditions include, for example, cancers” (Para. (150). Buis teaches a method comprising “The terms “subject” and “patient”, as used herein, refer to any animal, such as a dog” (Para. 116).
Buis teaches a method comprising “a) obtaining a nucleic acid sample isolated from a subject” (Para. 8). Buis teaches a method wherein “sample comprises at least one nucleic acid sequence whose genome is suspected of having undergone variation ... samples from any mammal, including, but not limited to dogs ... cell-free DNA may be isolated from the sample prior to further analysis)” (Para. 118).
Buis teaches a method comprising “c) hybridizing an anchor primer ... and hybridizing a genome-informed primer, which is substantially complementary to a repeat sequence in the nucleic acid, to produce a plurality of replicons, wherein the anchor sequence and the repeat sequence flank a gap region in the plurality of target nucleic acid sequences of interest; d) sequencing a plurality of amplicons that are amplified from the replicons in step c)” (Para. 10-11) and “wherein the repeat sequence is selected from the group consisting of Alu repeats” (Para. 12). “Alu repeats” read on SINE sequences and one of the most common SINE sequences in mammals.
Buis teaches a method comprising “further comprising determining the number of the unique amplicons sequenced at step d); determining a read density based at least in part on the number of unique amplicon sequences; and detecting copy number variation by comparing the read density to a plurality of reference read densities that are computed based on reference nucleic acid samples isolated from reference subjects” (Para. 12). Furthermore, Buis teaches a method comprising “one can align the DNA to the genome using standard or custom methods” (Para. 303). Buis teach a method comprising “a subject has a predisposition to a disease or condition that is associated with ... CNV [copy number variation] status ... Particular diseases and conditions include, for example, cancers” (Para. 150). Buis also teaches a method comprising “wherein reference value is from one or more cancer-free subjects” (Para. 16) and “the sample comprises at least one nucleic acid sequence whose genome is suspected of having undergone variation… used to detect a disease or condition, or detect the state of a disease or condition, or determine whether a subject has a predisposition to a disease or condition, in samples from any mammal” (Para. 118).
Thus, Buis suggests a method of identifying the number and distribution of short interspersed nuclear element (SINE) sequences in canine genomic sequences, comprising: isolating circulating cell free DNA (cfDNA) in from a biological sample taken from a canine animal, wherein the sample contains canine genomic sequences; amplifying SINE sequences and unique genomic sequences adjacent to each SINE sequence from the canine genomic sequences to determine the number and distribution of SINE sequences in the canine genomic sequences, wherein the unique genomic sequence adjacent to each SINE sequence is used to map where a SINE sequence has inserted itself into the genome of the canine animal; and determining whether the companion animal is likely to have cancer based on the number and distribution of the SINE sequences as compared to the number and distribution of the SINE sequences in a healthy animal.
Therefore, the invention as recited in claim 12 is prima facie obvious over the prior art Buis et al One of ordinary skill in the art would have had a reasonable expectation of success given these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and would have yielded the predictable outcome according to the limitations of claim 1-3, 6-7 and 10-11 in view of the teachings of Buis et al.. It would have been obvious to identify the number and distribution of short interspersed nuclear element (SINE) sequences in canine genomic sequences according to the limitations of the instant application claim 12 based on Buis et al. (Patent App. Pub. No. US 20190309352 A1).
The teachings of Buis are documented above in the rejection of claim 12 under 35 U.S.C. 103. Claim 13 depends on claim 12.
Regarding claim 13, Buis teaches a method wherein “sample is a blood sample” (Para. 118). Thus, Buis suggests a method wherein the biological sample is a blood sample.
Therefore, the invention as recited in claims 12-13 are prima facie obvious over the prior art Buis et al. One of ordinary skill in the art would have had a reasonable expectation of success given these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and would have yielded the predictable outcome according to the limitations of claims 12-13 in view of the teachings of Buis et al.. It would have been obvious to identify the number and distribution of short interspersed nuclear element (SINE) sequences in canine genomic sequences according to the limitations of the instant application claim 12-13 based on Buis et al. (Patent App. Pub. No. US 20190309352 A1).
Response to Arguments
Applicant's arguments filed 05/18/2026 have been fully considered but they are not
persuasive. Arguments against Buis on Pg. 8-10 are not persuasive as discussed above.
Claim(s) 4-5 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Buis et al. (“Buis”; Patent App. Pub. US 20190309352 A1, Oct. 10, 2019, filed on Nov. 16, 2017) as applied to claims 1-3, 6-7 and 10-11 in view of Mounts et al. (“Mounts”; Patent App. Pub. US 20070009899 A1, Jan. 11, 2007)
The teachings of Buis are documented above in the rejection of claims 1-3, 6-7 and 10-11 under 35 U.S.C. 103. Claims 4-5 and 8-9 depend on claim 2, which depends on claim 1. However, Buis does not explicitly teach the limitation SEQ ID NO:1.
Mounts discloses “The present invention provides nucleic acid arrays and methods of using the same for detecting gene expression in animal models of osteoarthritis or other inflammatory diseases. The nucleic acid arrays of the present invention comprise polynucleotide probes for genes that are differentially expressed in osteoarthritis-affected cartilage tissues as compared to non-osteoarthritic cartilage tissues. In one embodiment, a nucleic acid array of the present invention comprises a plurality of polynucleotide probe sets, each of which is capable of hybridizing under stringent or nucleic acid array hybridization conditions to a different respective tiling sequence selected from Table C, or the complement thereof.” (Abstract).
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Regarding claims 4-5, Mounts teaches a method wherein “The probes in Table I are perfect match probes and correspond to SEQ ID NOs: 12,312-210,107” (Para. 130) and SEQ ID NO: 219902 of sequence listing comprises a nucleic acid of 100% identity to SEQ ID NO: 1 of the instant application”, where “S” is a “G” (see alignment below).
Thus, Buis and Mounts suggest a method wherein the sequence specific primer has a nucleotide sequence of any one of SEQ ID NOs: 1-10, or a sequence having at least 90% sequence identity thereof; and wherein the sequence specific primer has a nucleotide sequence of SEQ ID NO: 1
Regarding claims 8 and 9, Buis teaches a method wherein “Following hybridization, a polymerase and a ligase are added under extension/ligation conditions” (Para. 67). Mounts teaches a method wherein “The probes in Table I are perfect match probes and correspond to SEQ ID NOs: 12,312-210,107” (Para. 130) and SEQ ID NO: 219902 of sequence listing comprises a nucleic acid of 100% identity to SEQ ID NO: 1 of the instant application”, where “S” is a “G” (see alignment above). Thus, Buis and Mounts suggest a method wherein determining the number and distribution of the copies of amplified regions comprises performing a single primer extension using any one or more of SEQ ID NOs: 1-10, or a sequence having at least 90% sequence identity thereof, as a portion of the primer being extended; and wherein determining the number and distribution of the copies of amplified regions comprises performing a single primer extension using SEQ ID NO: 1 as a portion of the primer being extended.
Buis and Mounts are both considered to be analogous to the claimed invention because they are in the same field of determining whether a subject is predisposed to the disease or condition. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of isolating cfDNA, amplifying the cfDNA SINE sequences and adjacent regions, comparing the copies of amplified regions of the dog suspected of having cancer to a healthy animal and determining the difference which indicates the companion animal is likely to have cancer as taught by Buis to incorporate the method wherein the primer sequence is SEQ ID NO: 1 of the instant application as taught by Mounts and provide a method of determining if a companion animal is likely to have cancer. One of ordinary skill in the art would have had a reasonable expectation of success given these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and would have yielded the predictable outcome according to the limitations of claim 4-5 and 8-9 in view of the teachings of Buis et al. and Mounts et al. Doing so would allow for the diagnosis of cancer in a companion dog using a specific canine SINE sequences.
Response to Arguments
Applicant's arguments filed 05/18/2026 (Pg. 9) with respect to claims 4-5, 8-9 and 14-15 have been fully considered but they are not persuasive. To clarify some instances argued in the response filed 05/18/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “Mounts fails to make up for the deficiencies of Buis. Mounts appears to have been cited only for its disclosure of SEQ ID NO: 219902 of the sequence listing which the Office Action states corresponds to a nucleic acid probe of 100°/o identity to SEQ ID NO: 1 of the instant application. In view of the enormous number of possible nucleotide probes which Mounts discloses can be included in the nucleic acid array, in the absence of the teachings of the present application, one of ordinary skill in the art would not be motivated to particularly select SEQ ID NO: 219902 in Mounts to use in the claimed invention” (Pg. 19-20)
Response: Applicant’s arguments have been fully considered and found unpersuasive because as stated in the revised rejection above on Pg. 22-23 “Buis and Mounts are both considered to be analogous to the claimed invention because they are in the same field of determining whether a subject is predisposed to the disease or condition. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of isolating cfDNA, amplifying the cfDNA SINE sequences and adjacent regions, comparing the copies of amplified regions of the dog suspected of having cancer to a healthy animal and determining the difference which indicates the companion animal is likely to have cancer as taught by Buis to incorporate the method wherein the primer sequence is SEQ ID NO: 1 of the instant application as taught by Mounts and provide a method of determining if a companion animal is likely to have cancer. These claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome according to the limitations of claims 4-5 and 8-9. Doing so would allow for the diagnosis of cancer in a companion dog using a specific canine SINE sequences.” Thus, one of ordinary skill in the art would be motivated to particularly select SEQ ID NO: 219902 in Mounts to use in the claimed invention.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Buis et al. (“Buis”; Patent App. Pub. US 20190309352 A1, Oct. 10, 2019, filed on Nov. 16, 2017) as applied to claims 12-13, and further in view of Mounts et al. (“Mounts”; Patent App. Pub. US 20070009899 A1, Jan. 11, 2007)
The teachings of Buis are documented above in the rejection of claims 12-13 under 35 U.S.C. 103. Claim 14-15 depend on claim 12. Buis does not explicitly teach the limitations of SEQ ID NO:1.
Mounts discloses “The present invention provides nucleic acid arrays and methods of using the same for detecting gene expression in animal models of osteoarthritis or other inflammatory diseases. The nucleic acid arrays of the present invention comprise polynucleotide probes for genes that are differentially expressed in osteoarthritis-affected cartilage tissues as compared to non-osteoarthritic cartilage tissues. In one embodiment, a nucleic acid array of the present invention comprises a plurality of polynucleotide probe sets, each of which is capable of hybridizing under stringent or nucleic acid array hybridization conditions to a different respective tiling sequence selected from Table C, or the complement thereof.” (Abstract).
Regarding claim 14, Mounts teaches a method wherein “The probes in Table I are perfect match probes and correspond to SEQ ID NOs: 12,312-210,107” (Para. 130) and SEQ ID NO: 219902 of sequence listing comprises a nucleic acid of 100% identity to SEQ ID NO: 1 of the instant application”, where “S” is a “G” (see alignment below). Thus, Buis and Mounts teach a method wherein the sequence specific primer has a nucleotide sequence of any one of SEQ ID NOs: 1-10, or a sequence having at least 90% sequence identity thereof.
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Regarding claim 15, Mounts teaches a method wherein “The probes in Table I are perfect match probes and correspond to SEQ ID NOs: 12,312-210,107” (Para. 130) and SEQ ID NO: 219902 of sequence listing comprises a nucleic acid of 100% identity to SEQ ID NO: 1 of the instant application”, where “S” is a “G” (see alignment above).Thus, Buis and Mounts teach a method wherein the sequence specific primer has a nucleotide sequence of SEQ ID NO: 1
Buis and Mounts are both considered to be analogous to the claimed invention because they are in the same field of determining whether a subject is predisposed to the disease or condition. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of obtaining CfDNA, amplifying the cfDNA, comparing the copies of amplified regions to a healthy animal and determining the difference which indicates the companion animal is likely to have cancer as taught by Buis to incorporate the method wherein the primer sequence is SEQ ID NO: 1 of the instant application as taught by Mounts and provide a method of determining if a companion animal is likely to have cancer. One of ordinary skill in the art would have had a reasonable expectation of success given these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and would have yielded the predictable outcome according to the limitations of claims 14-15 in view of the teachings of Buis et al. and Mounts et al. Doing so would allow for the diagnosis of cancer in a companion animal using a specific canine sequence.
Response to Arguments
Applicant's arguments filed 05/18/2026 have been fully considered but they are not
persuasive. Arguments against Buis and Mounts on Pg. 9 are not persuasive as discussed above.
Conclusion of Response to Arguments
In view of the amendments, new grounds, maintained and revised rejections and above responses to arguments, no claims are in condition for allowance.
Conclusion
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 KENDRA R VANN-OJUEKAIYE whose telephone number is (571)270-7529. The examiner can normally be reached M-F 9:00 AM- 5:00 PM.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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