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 the national phase of PCT/US2021/019846, filed 02/26/2021, claiming priority to US provisional application 62/982,985, filed 02/28/2020. The International Search Report and Written Opinion issued in the PCT application have been received and reviewed.
Election/Restrictions
Applicant’s election without traverse of the species of the E4-E2 fusion comprising SEQ ID NO: 22 and the primer pair of SEQ ID NO: 3 and SEQ ID NO: 4 in the reply filed on 23 September 2025 is acknowledged. Claims 1-3, 5-8, and 12-21 are under consideration herein as directed to the elected species.
Claims 4, 9-11, and 25-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 25 September 2025.
Comment Regarding Drawings
It is noted that the Drawings filed 29 August 2022 have been accepted despite the lack of SEQ ID NOS noted below, as the required sequence identifiers may be added to the specification (i.e., replacement of the drawing itself is not required if the SEQ ID NOS are added to the description of the figure).
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figure 2A-C.
Required response – Applicant must provide:
Replacement and annotated 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 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
Regarding claim 1 and claims dependent therefrom (and with particular reference to dependent claims 4-6), it is noted that the limitation “the detection” in b) of claim 1 has been interpreted as referring to the “detecting” of b) of the claim, as this is the only reasonable interpretation of the claim language (and the limitation “the detection” in each of claims 4-6 is also interpreted as referring back to and further limiting this “detecting”). It is also noted that the specification states that (see paragraph 85 of the corresponding published application):
As used herein, the term “detecting” refers to detection of a level of a fusion (e.g., the fusion of a BCL2L14 polynucleotide sequence and a ETV6 polynucleotide) that is at least about 5% (e.g., at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 200%, at least about 300%, at least about 400%, at least about 500%, at least about 600%, at least about 700%, at least about 800%, at least about 900%, at least about 1000%, at least about 2000%, at least about 3000%, or at least about 5000%) or at least about 5 times (e.g., at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 20 times, at least about 30 times, at least about 40 times, at least about 50 times, or at least about 100 times) higher as compared to a sample from a subject in general or a study population (e.g., healthy control).
Based on this definition as well as the language of the claims and the content of the specification as a whole (in which the term “detecting” is employed only in reference to physical/active types of “detecting” nucleic acid or protein products), the term “detecting a BCL2L14/ETV6 gene fusion in the/a sample” has been interpreted as requiring the detecting of the physical presence of such a fusion in a (biological) sample at a level that is “at least about” 5% or 5 times higher “as compared to a sample from a subject in general or a study population”.
Regarding all claims as directed to the elected species, it is noted that the term “E4-E2 fusion” is interpreted in accordance with the definition provided in the specification (see, e.g., paragraph 81 of the corresponding published application), which recites: “a fusion of exons 1-4 of a BCL2L14 polynucleotide with exons 2-8 of a ETV6 polynucleotide (referred to herein as an “E4-E2 fusion”)”.
Regarding claims 5-6, it is noted that the claims recite “two primers, wherein the first primer….and the second primer….”. While the claims do not provide literal antecedent basis for the recitations of first and second primers, given the immediate prior reference to “two primers”, the recitations of “the first primer” and “the second primer” have been interpreted as referring to first and second primers of the required “two primers”. (However, please note the indefiniteness rejection that applies to claim 7 below, as this claim does require clarification.)
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 5-8 and 19 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.
Claims 5 and 7-8 (which dependent from claim 5) are indefinite over the recitation in claim 5 of the limitation “wherein the BCL2L14/ETV6 gene fusion is detectable by the presence of an amplicon generated by the first primer and the second primer”, because it is unclear how this limitation further limits the claims. More particularly, some persons of skill in the art would interpret this language as requiring that the “contacting” with first and second primers actual result in production of an amplicon, whereas others would interpret this language as reciting a property of the fusion (as the wording of the claim reasonably encompasses both of these interpretations). As there are multiple reasonable interpretations of the claim language that impart different types of boundaries on what is being claimed (one resulting in a manipulative difference and one not), further clarification is required.
Claim 6 is indefinite over the recitation of the limitation “wherein hybridization of the two primers on a BCL2L14/ETV6 gene fusion sequence provides a detectable signal, and the BCL2L14/ETV6 gene fusion is detectable by the presence of the signal”, because it is unclear how this limitation further limits the claim. More particularly, some persons of skill in the art would interpret this language as requiring that such a hybridization actually occur (resulting in production of a detectable signal), while others would interpret this language as reciting a property of the two primers when hybridized to the fusion (as the wording of the claim reasonably encompasses both of these interpretations). As there are multiple reasonable interpretations of the claim language that impart different types of boundaries on what is being claimed (one resulting in a manipulative difference and one not), further clarification is required.
Claim 7 is indefinite over the recitation of the limitation “the one or more primers” (see lines 1-2 and 4) because there is insufficient antecedent basis for this limitation in claim 5 (from which claim 7 depends). It is noted that claim 5 recites “two primers” as well as a “first primer” and a “second primer”; however, antecedent basis is lacking for “the one or more primers”. This rejection could be overcome by simply amending claim 7 to reference “the first primer” and “the second primer” (as there is basis for these terms in claim 5).
Claim 19 is indefinite over the recitation of the limitations “the E2-E3 fusion”, “the E2-E6 fusion”, “the E4-E2 fusion” (which corresponds to the elected species), “the E4-E3 fusion”, and “the E5-E5 fusion”, as there is insufficient antecedent basis for these limitations in claim 17 (from which claim 19 depends). It appears that claim 19 may have been intended to depend from claim 18 (and amendment of the claim to depend from claim 18 would overcome this rejection).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 and 12-14 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Chinnaiyan et al (US 2013/0096021 A1 [18 April 2013; filed 27 Sept. 2012]; cited in IDS).
Chinnaiyan et al disclose methods of detecting gene fusions “as diagnostic markers and clinical targets for breast cancer” (see entire reference, particularly the Abstract and Summary at paragraphs 10-12). Among the methods taught by Chinnaiyan et al are methods comprising performing a nucleic acid (or protein) detection assay on a biological sample from a subject to detect/identify a BCL2L14-ETV6 fusion (which methods may further comprise determining a “treatment course of action based on the presence or absence of the gene fusion”, and administering an inhibitor targeting the fusion when detected) (see paragraphs 12, 63, 184 [noting the reference to Table 1], claims 10-14, and Tables 1, 4-5, and 10). With further regard to the “obtaining” of independent claim 1, Chinnaiyan et al teach that samples for use in their methods may be obtained from any source, including preferred samples of breast biopsy samples or other breast tissue samples (see, e.g., paragraphs 54 and 78-79). Regarding the “detecting” of independent claim 1, Chinnaiyan et al teach a variety of well-known methods that may be applied to detecting their disclosed gene fusions, including nucleic acid sequencing, hybridization, amplification, etc. (see, e.g., paragraphs 80-110). With further regard to both claim 1 and dependent claims 12-14, Chinnaiyan et al disclose perform their methods on biological samples from subjects with triple negative breast cancer (see paragraphs 58, 181, and 184 [noting the reference to Table 1], as well as paragraph 192), and Table 1 reports detection of a BCL2L14-ETV6 fusion in a triple negative breast cancer tumor (see Table 1, and see also Example 2 at Table 10).
Chinnaiyan et al thus anticipate claims 1 and 12-14. While it is noted that independent claim 1 recites “wherein the detection indicates the subject has increased paclitaxel resistance and the subject is diagnosed with increased paclitaxel resistance”, this “wherein” language simply states what is indicated by the result of the “detecting”; as this claim language does not require steps to be performed, it is not limiting of claim scope (see MPEP 2111.04). Additionally, the requirements of the “wherein” clause are inherently met as a result of the performance of the active step of “detecting a BCL2L14/ETV6 gene fusion in the sample” of b), and the “diagnosis” referenced in the “wherein” clause and preamble constitute instructional limitations added to a method known in the art, i.e., non-functional descriptive material that is not given patentable weight (see MPEP 2111.05). Furthermore, the recitation in the preamble of “diagnosing a subject” in the context of the present claim does not result in a manipulative difference (such that patentable weight is not given), as again, the recitation “subject is diagnosed” simply states a conclusion regarding the subject that results from the active “detecting” of the claim (see MPEP 2111.02(II)).
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) 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Chinnaiyan et al (US 2013/0096021 A1 [18 April 2013; filed 27 Sept. 2012]; cited in IDS) in view of Reeve et al (WO9947706A1 [Sept 1999]; cited herein).
Regarding independent claim 1 (from which claims 5-6 depend), Chinnaiyan et al disclose methods of detecting gene fusions “as diagnostic markers and clinical targets for breast cancer” (see entire reference, particularly the Abstract and Summary at paragraphs 10-12). Among the methods taught by Chinnaiyan et al are methods comprising performing a nucleic acid (or protein) detection assay on a biological sample from a subject to detect/identify a BCL2L14-ETV6 fusion (which methods may further comprise determining a “treatment course of action based on the presence or absence of the gene fusion”, and administering an inhibitor targeting the fusion when detected) (see paragraphs 12, 63, 184 [noting the reference to Table 1], claims 10-14, and Tables 1, 4-5, and 10). With further regard to the “obtaining” of independent claim 1, Chinnaiyan et al teach that samples for use in their methods may be obtained from any source, including preferred samples of breast biopsy samples or other breast tissue samples (see, e.g., paragraphs 54 and 78-79). Regarding the “detecting” of independent claim 1, Chinnaiyan et al teach a variety of well-known methods that may be applied to detecting their disclosed gene fusions, including nucleic acid sequencing, hybridization, amplification, etc. (see, e.g., paragraphs 80-110). It is also noted that (given that triple negative breast cancer is a preferred embodiment) Chinnaiyan et al disclose perform their methods on biological samples from subjects with triple negative breast cancer (see paragraphs 58, 181, and 184 [noting the reference to Table 1], as well as paragraph 192), and Table 1 reports detection of a BCL2L14-ETV6 fusion in a triple negative breast cancer tumor (see Table 1, and see also Example 2 at Table 10).
Chinnaiyan et al thus teach a method meeting all of the requirements of independent claim 1. While it is noted that claim 1 recites “wherein the detection indicates the subject has increased paclitaxel resistance and the subject is diagnosed with increased paclitaxel resistance”, this “wherein” language simply states what is indicated by the result of the “detecting”; as this claim language does not require steps to be performed, it is not limiting of claim scope (see MPEP 2111.04). Additionally, the requirements of the “wherein” clause are inherently met as a result of the performance of the active step of “detecting a BCL2L14/ETV6 gene fusion in the sample” of b), and the “diagnosis” referenced in the “wherein” clause and preamble constitute instructional limitations added to a method known in the art, i.e., non-functional descriptive material that is not given patentable weight (see MPEP 2111.05). Furthermore, the recitation in the preamble of “diagnosing a subject” in the context of the present claim does not result in a manipulative difference (such that patentable weight is not given), as again, the recitation “subject is diagnosed” simply states a conclusion regarding the subject that results from the active “detecting” of the claim (see MPEP 2111.02(II)).
While Chinnaiyan et al teach a variety of methods that ma be employed in detecting their disclosed fusions, including nucleic acid sequencing (as noted above), Chinnaiyan et al do not teach a “detecting” that employs a reaction mixture including primers meeting the requirements of claims 5-6.
Reeve et al teach compositions, including arrays, comprising all possible “N mer” oligonucleotides or subsets thereof “where N is preferably from 5 to 10, particularly 8 or 9” (see entire reference, particularly pages 4-5; quotation from page 5, lines 10-11). Reeve et al teach that their N mers may be DNA, RNA, PNA or “mimetics or mixtures thereof” (see page 5, lines 12-13), and state that the molecules may be in solution (page 4) or "immobilised at a spaced location on a surface of a support” (page 5). Reeve et al disclose the use of their reagents in sequencing by hybridization, and particularly in determining difference between target and reference sequences (see entire reference, particularly, e.g., pages 2-3). The method disclosed by Reeve et al comprises incubating together "under hybridisation conditions" target nucleic acid obtained from a sample and an oligomer composition of Reeve et al to determine the nucleic acid sequence of a target (see pages 2-7). Further, the compositions of Reeve et al encompass, e.g., the use of all possible 10mers, such that the compositions of Reeve et al inherently include multiple primers meeting the requirements of claims 5-6 (as the claims simply require primers “complementary to” the recited target sequences). The sequencing method of Reeve et al thus includes the use of primers meeting the requirements of applicant’s claims. It is also noted that (while claims 5-6 are indefinite for the reasons indicated above) Reeve et al disclose embodiments of their invention in which target sequences are amplified using compositions of labeled Nmers (see, e.g., pages 3-4), as well as embodiments of their methods in which each of their oligonucleotides includes a label, and in which the labeled oligonucleotides are hybridized and the labels subsequently observed and measured (see, e.g., pages 2-3 and 5-6).
In view of the teachings of Reeve et al, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified the method of Chinnaiyan et al so as to have substituted the sequencing method of Reeve et al for that taught by Chinnaiyan et al, and thereby to have performed a method meeting the requirements of instant claims 5-6. As both the sequencing methodologies taught by Chinnaiyan et al and that taught by Reeve et al were sequencing methods known to those of ordinary skill in the art at the time the invention was made, an ordinary artisan would have recognized such a modification as the simple substitution of one known sequencing technique for another to achieve the predictable result of sequencing (and thereby identifying and detecting) the target fusions taught by Chinnaiyan et al.
Claim(s) 2, 15, 17-18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Chinnaiyan et al in view of Nik-Zainal et al (US 2019/0345562 [14 Nov 2019; filed 22 Dec 2017]; cited herein)
The relevant teachings of Chinnaiyan et al are set forth above. With particular regard to independent claim 17 and claims dependent therefrom, it is noted that Chinnaiyan et al’s disclosures of a “detecting” of a fusion (as set forth in a) of claim 17) meeting the requirements of the claims – including with regard to a sample from a subject with triple negative breast cancer, as set forth in dependent claims 20-21 - are set forth above. However, Chinnaiyan et al do not teach an “administering” meeting the requirements of claim 17 and its dependent claims (or of claim 15, dependent from claim 1). Further, Chinnaiyan et al do not disclose detecting fusion constructs as specified in dependent claims 2 and 18.
Nik-Zainal et al teach detection and classification of breast (and ovarian) cancers as deficient in homologous repair (“HR-deficient”) based on the detection of “rearrangement signatures” that occur as “hotspots” in the cancer genome (see entire reference, particularly the Abstract and the Summary at paragraphs 4-5). Nik-Zainal et al teach that detection of such rearrangement signatures may “inform decisions on treatment, since some agents are more effective against” such cancers (paragraph 4; see also paragraphs 11-15).
Regarding the elected E4-E2 fusion constructs of dependent claims 2 and 18, Nik-Zainal et al teach a breast cancer rearrangement signature hotspot, “B4”, that includes both BCL2L14 and ETV6; see paragraphs 65, 77, 87-107, and Table 1 at page 20, noting that Nik-Zainal et al generally disclose testing for any possible rearrangements/fusions/breakpoints involving their disclosed hotspots. In view of the teachings of Chinnaiyan et al and Nik-Zainal 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 performed a “detecting” as claimed with regard to any type of BCL2L14/ETV6 fusion, including an E4-E2 fusion, and thereby to have performed a method including “detecting” a fusion as claimed. While neither of the references explicitly reports detecting such a fusion, the teachings of Chinnaiyan et al establish that fusions of BCL2L14/ETV6 occur in the context of triple negative breast cancer, and Nik-Zainal et al disclose grouping these two genes together in a breast cancer rearrangement signature “hotspot”, which would have motivated one of ordinary skill in the art to have conducted detection/testing with regard to any such fusion (including an E4-E2 fusion), regardless of the specific fusion points involved. An ordinary artisan would have been motivated to have conducted such “detecting” for the benefit of characterizing the specific genetic structure(s) underlying a subject’s breast cancer, thereby facilitating, e.g., more appropriate treatment of the subject (as is suggested by both the teachings of Nik-Zainal et al and the teachings of Chinnaiyan et al).
Regarding the “administering” of independent claim 17, as well as claim 15 (dependent from independent claim 1), it is first noted that the claims as written do not require that the recited steps be performed in any particular order, such that the “administering” may be performed before or after the other recited steps of the claims. With regard to an “administering” as required by claims 15 and 17, it is noted that among the types of treatments taught by Nik-Zainal et al are administration of the PARP inhibitors olaparib and talazoparib, and the platins carboplatin and cisplatin, which treatments are taught as being among the types of therapies exhibiting greater efficacy against HR-deficient cancers (i.e., those characterized by the “hotspots” discussed by Nik-Zainal et al) as compared to HR-proficient cancers (see, e.g., paragraphs 128-132). In view of these teachings of Nik-Zainal 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 further modified the methods suggested by Chinnaiyan et al and Nik-Zainal et al so as to have employed any of the known breast cancer therapies taught by Nik-Zainal et al as particularly appropriate for subjects with HR-deficient breast cancer, and thereby to have performed methods meeting the requirements of the claims. An ordinary artisan would have been motivated to have made such a modification for the benefit of more appropriately treating the cancer of a subject exhibiting a BCL2L14/ETV6 fusion, as is suggested by the teachings of both references.
Claim(s) 16 is rejected under 35 U.S.C. 103 as being unpatentable over Chinnaiyan et al in view of Nik-Zainal et al, as applied to claims 2, 15, 17-18, and 20-21, above, and further in view of Li et al (J. Transl. Med. 16:147 [2018]; cited herein).
The teachings of Chinnaiyan et al and Nik-Zainal et al are set forth above. While each of Chinnaiyan et al and Nik-Zainal et al teach that their methods have applications in selecting appropriate therapy for breast cancer, with Chinnaiyan et al also disclosing detection of a BCL2L14/ETV6 fusion in triple negative breast cancer, and Nik-Zainal et al teachings the use of PARP inhibitors in treating HR-deficient breast cancers, neither of these references specifically discloses administering an immune checkpoint inhibitor.
Li et al provide an overview of immunotherapeutic interventions for triple negative breast cancer (see entire reference). Li et al teach that immune checkpoint inhibitors may be used in combination with other targeted treatments (see pages 5-8), and particularly teach the use of anti-PD-1/PD-L1 mAbs in combination with PARP inhibitors (i.e., one of the therapy types taught by Nik-Zainal et al) to treat HR-deficient triple negative breast cancer, stating that the additional of anti-PD-1/PD-L1 mAbs “may exert a supplementary and increased antitumour effect in combination with a PARP inhibitor” (see page 7, right column-page 8, left column). In view of these teachings of Li 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 further modified the methods suggested by Chinnaiyan et al and Nik-Zainal et al so as to have employed in combination with a PARP inhibitor as taught by Nik-Zainal et al an immune checkpoint inhibitor as taught by Li et al when treating a subject with triple negative breast cancer (either before or after the “detecting” required by the claim). An ordinary artisan would have been motivated to have made such a modification for the benefit of providing supplementary and increased antitumor activity when treating the subject, as taught by Li et al.
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 1-3, 5-6, and 12-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural phenomenon/law of nature without significantly more. The claim(s) recite(s) “diagnosing a subject with increased paclitaxel resistance” as well as a “detecting” that is followed by the recitation “wherein the detection indicates the subject has increased paclitaxel resistance and the subject is diagnosed with increased paclitaxel resistance”. Such a diagnosing/diagnosis constitutes a mental conclusion drawn regarding what is indicated by detection of a naturally occurring gene fusion, i.e., an abstract idea (an activity that may be performed entirely in the human mind) regarding a natural phenomenon/law of nature (the occurrence of a gene fusion that is associated with drug resistance). This judicial exception (JE) is not integrated into a practical application because the only active steps of the claim, of “obtaining a biological sample” and “detecting” the gene fusion, are data gathering steps that constitute insignificant extra-solution activity; there are not actions required by the claims that constitute any type of application/implementation of the JEs of the claims. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the active steps of the claims, whether considered individually or in combination, constituted well-understood, routine, and conventional activity before Applicant’s effective filing date (see, e.g., Chinnaiyan et al, cited above). With further regard to dependent claims 2-3, these claims simply recite further characteristic of a naturally occurring gene fusion; no practical application is set forth, and nothing “significantly more” than a JE is present in the claims. While it is noted that the particular elected gene fusion of SEQ ID NO: 22 was not known in the prior art, the recitation of this sequence is the recitation of a naturally occurring fusion sequence (i.e., a more particular JE, rather than something more than a JE). See MPEP 2106.05(I), noting that an inventive concept may not be furnished by a law of nature/natural phenomenon/abstract idea itself. Regarding claims 5-6, these claims recite more particular types of data gathering (rather than any type of application of a JE), and as primers meeting the requirements of the claims (and the use thereof in a manner meeting the requirements of the claims) was well-known before Applicant’s effective filing date, nothing “significantly more” than a JE is added (although it is noted that claims 7-8, reciting the specific elected primers of SEQ ID NOS 7-8, have been excluded from this rejection). Regarding claims 12-14, these claims simply recite a more particular type of subject from whom a sample for testing is obtained; nothing amounting to a practical application or something “significantly more” than a JE is required. Regarding claims 15-16, while these claims recite further active steps of “administering”, there is no requirement that such administering correspond to an implementation/application of the JEs of claim 1 (for example, the “administering” may be performed prior to obtaining the sample for testing). Additionally, the claims reciting “administering” steps that correspond to well-understood, routine, and conventional activities (see, e.g., of Nik-Zainal et al and Li et al, cited above). Thus, none of claims 1-3, 5-6, and 12-16 is directed to patent eligible subject matter. (With regard to independent claim 17 and claims dependent therefrom, it is noted that this claim also recites an “administering” that may be performed either before or after the “detecting’ of the claim; however, claim 17 does not recite a judicial exception).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Romero et al (The American Journal of Pathology 188(1):2378 [Oct 2018]; cited herein) disclose that medullary breast carcinoma (a type of triple negative breast cancer) is associated with overexpression of BCLG (i.e., BCL2L14) (see entire reference). Letessier et al (Genes, Chromosomes & Cancer 44:103-108 [2005]; cited herein) discloses that the ETV6 gene is frequently rearranged in cancer, including in invasive breast cancer (see entire reference).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DIANA B JOHANNSEN whose telephone number is (571)272-0744. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm EST.
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682