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 .
Election/Restrictions
Applicant’s election without traverse of group 2, MYC; " A targeted therapy that inhibits expression and/or activity of a protein product of, or activation of one or more signaling pathways stimulated by, MYC;" The targeted therapy comprises an inhibitor of expression and/or activity of a protein product of MYC; " Diffuse large B-cell lymphoma (DLBCL); and " A nucleic acid sample in the reply filed on 1/2/2026 is acknowledged.
Claims 15, 17, 32-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 1/2/2026.
Claims 16, 19, 25, 26, 29-31, 38, 50, 52, 57, and 58are being examined.
Priority
The instant application was filed 06/15/2023 and is a national stage entry of PCT/US2021/064657 with an international filing date: 12/21/2021 and claims priority from provisional application 63129286 , filed 12/22/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/31/2023 and 1/28/2026 are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims16, 19, 25, 26, 29-31, 38, 50, 52, 57 objected to because of the following informalities:
Claim 1 is objected to as it recites “IGH” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Claim 25 is objected to as it recites “CCND1, MYEOV, MYC, MAF, MAFB, BCL6, BCL2, FGFR3, WHSC1, BCL3, NBEAP1, BCL10, BCL11A, CCND2, CCND3, CCNE1, CD44, CDK6, CEBPA, CEBPB, CEBPD, CEBPE, CRLF2, ID4, DDX6, DUX4, EPOR, GPR34, FCRL4, FCGR2B, IRF4, IRF8, CD274, PDCD1LG2, LHX2, LHX4, PAX5, IGF2BP1, TNFSF13, MALT1, FOXP1,IL3, miR-125b-1, MUC1, SOX5, or MYCN.” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Claim 29 is objected to as it recites “CCND1, MYEOV, MYC, MAF, MAFB, BCL6, BCL2, FGFR3, WHSC1, BCL3, NBEAP1, BCL10, BCL11A, CCND2, CCND3, CCNE1, CD44, CDK6, CEBPA, CEBPB, CEBPD, CEBPE, CRLF2, ID4, DDX6, DUX4, EPOR, GPR34, FCRL4, FCGR2B, IRF4, IRF8, CD274, PDCD1LG2, LHX2, LHX4, PAX5, IGF2BP1, TNFSF13, MALT1, FOXP1,IL3, miR- 125b-1, MUC1, SOX5 or MYCN.” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Claim 31 is objected to as it recites “DLBCL, “,” ALL, B-ALL, NHL, MCL”, “ MPN, “, CLL” but does not recite the full terminology for the acronym (or abbreviation). Claims are more concise when the first time an acronym (or abbreviation) is presented the full terminology is also presented. Finally an acronym (or abbreviation) may have alternative meanings to an artisan.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 16, 19, 25, 26, 29-31, 38, 50, 52, 57, and 58 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
As set forth in In re Alonso 88 USPQ2d 1849 (Fed. Cir. 2008), at 1851:
The written description requirement of 35 U.S.C. § 112, ¶ 1, is straightforward: “The specification shall contain a written description of the invention ….” To satisfy this requirement, the specification must describe the invention in sufficient detail so “that one skilled in the art can clearly conclude that the inventor invented the claimed invention as of the filing date sought.” Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997); see also LizardTech, Inc. v. Earth Res. Mapping, Inc., 424 F.3d 1336, 1345 [76 USPQ2d 1724] (Fed. Cir. 2005); Eiselstein v. Frank, 52 F.3d 1035, 1039 [34 USPQ2d 1467] (Fed. Cir. 1995).
Alonso at 1852:
A genus can be described by disclosing: (1) a representative number of species in that genus; or (2) its “relevant identifying characteristics,” such as “complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” Enzo, 323 F.3d at 964.
In applying the test as set forth in Alonso, it is noted that applicant is claiming method of treating or delaying progression of cancer, comprising:(a) detecting a presence of a translocation comprising a first breakpoint in the IGH locus and a second breakpoint in a sample from an individual, wherein the second breakpoint is 1.3Mb or less from a transcription start site (TSSI of an oncogene; and (b) administering to the individual an effective amount of a targeted therapy that inhibits expression and/or activity of a protein product of the oncogene based at least in part on the detection of the second breakpoint 1.3Mb or less from the TSS of the oncogene in the sample..
Thus the claims encompass any IGH locus from any species and any oncogene from any species. These are both enormous genus.
Further the claim encompasses, “targeted therapy that inhibits expression and/or activity of a protein product of the oncogene.” This is an enormous genus as it encompasses any oncogene from any species.
The claims are not limited to any specific species. Burgin (Journal of Mammalogy, 99(1):1–14, 2018) teaches, “We found 6,495 species of currently recognized mammals.” Thus the claims encompass a genus of species of individuals or subjects.
The claim encompasses any oncogene. Wee (Life Sciences (2018) 211, pages 206-214) teaches, “we found 637 oncogenes associated with CNVs in 5900 tumour samples.” Thus this is an enormous genus.
Further the claims require a targeted therapy. Dependent claims draw the invention to “the targeted therapy comprises (a) an antibody that specifically binds a protein product of the oncogene, (b) a compound that inhibits an activity of a protein product of the oncogene, or (c) a nucleic acid that inhibits expression of a protein product of the oncogene.” Further dependent claims are drawn to targeted therapy inhibits expression and/or activity of a protein product of, or activation of one or more signaling pathways stimulated by, CCND1, MYEOV, MYC, MAF, MAFB, BCL6, BCL2, FGFR3, WHSC1, BCL3, NBEAP1, BCL10, BCL11A, CCND2, CCND3, CCNE1, CD44, CDK6, CEBPA, CEBPB, CEBPD, CEBPE, CRLF2, ID4, DDX6, DUX4, EPOR, GPR34, FCRL4, FCGR2B, IRF4, IRF8, CD274, PDCD1LG2, LHX2, LHX4, PAX5, IGF2BP1, TNFSF13, MALT1, FOXP1,IL3, miR-125b-1, MUC1, SOX5, or MYCN. Thus this is an enormous genus.
The specification teaches inhibitors for PD1 (0255), MYC (279). However, the claims are not limited to these genes.
Thus while the claims encompass a large genus of species of individuals, large genus of oncogenes and large genus of targeted therapies, the specification does not adequate number of species or a structure function relationship of the species, oncogenes, and targeted therapy. Thus the claims lack adequate written description.
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 16, 19, 25, 26, 29-31, 38, 50, 52, 57, and 58 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 16 recites, “administering to the individual an effective amount of a targeted therapy that inhibits expression and/or activity of a protein product of the oncogene based at least in part on the detection of the second breakpoint 1.3Mb or less from the TSS of the oncogene in the sample.” The recitation of “based at least in part” is not an art accepted term. Review and searching of the specification did not reveal a definition or standard to determine what is inside or outside the scope of based at least in part. Thus the recitation is vague and unclear.
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 16, 19, 25, 26, 29-31, 38, 50, 52, 57, and 58 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation and mental step without significantly more. The claim(s) recite(s) the abstract idea or mental step of providing a targeted therapy based on the .presence of an IGH-oncogene translocaiton This judicial exception is not integrated into a practical application because administering to the individual an effective amount of a targeted therapy that inhibits expression and/or activity of a protein product of the oncogene based at least in part on the detection of the second breakpoint 1.3Mb or less from the TSS of the oncogene in the sample this is merely applying the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims provide any specific reagents or steps..
Claim analysis
The instant claim 16 is directed towards a method of treating or delaying progression of cancer, comprising:(a) detecting a presence of a translocation comprising a first breakpoint in the IGH locus and a second breakpoint in a sample from an individual, wherein the second breakpoint is 1.3Mb or less from a transcription start site (TSSI of an oncogene; and (b) administering to the individual an effective amount of a targeted therapy that inhibits expression and/or activity of a protein product of the oncogene based at least in part on the detection of the second breakpoint 1.3Mb or less from the TSS of the oncogene in the sample.
The recitation of “administering to the individual an effective amount of a targeted therapy that inhibits expression and/or activity of a protein product of the oncogene based at least in part on the detection of the second breakpoint 1.3Mb or less from the TSS of the oncogene in the sample” is a natural correlation and abstract idea. While it requires administering, the treatment is merely treating the translocation detected in the method.
The detecting a presence of a translocation comprising a first breakpoint in the IGH locus and a second breakpoint in a sample from an individual, wherein the second breakpoint is 1.3Mb or less from a transcription start site (TSS) of an oncogene can broadly encompass reading a report.
Dependent claims set forth further limitations with respect to how the inhibitor targets the oncogene, the oncogenes, inhibitors, type of cancer, etc. .
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? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract idea and/or law of nature or natural phenomena.
With regards to claim 16, the claim recites, “administering to the individual an effective amount of a targeted therapy that inhibits expression and/or activity of a protein product of the oncogene based at least in part on the detection of the second breakpoint 1.3Mb or less from the TSS of the oncogene in the sample.” This is an abstract idea or mental step of selecting treatment based on translocation..
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as the administering step is applying the judicial exception with a high level of generality.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No
The detecting a translocation can be considered a mental step, but at it can be interpreted to be an active step Chong (Blood Advances (2018) [ages 2755-2765) and Li ( Journal of Hematology & Oncology (2019) 12:73). Demonstrate it is routine and conventional.
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) 16, 19, 25, 26, 29-31, 38, 50, 52, 57, and 58 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chong (Blood Advances (2018) [ages 2755-2765) and Li ( Journal of Hematology & Oncology (2019) 12:73).
With regards to claim Chong teaches, “MYC rearrangements are known to have prognostic impact in DLBCL, previous large-scale studies examining their incidence and impact have mostly used break-apart fluorescence in situ hybridization (FISH) assays. These are able to detect the presence or absence of rearrangements but lack the resolution to identify the precise location of MYC breakpoints and require additional assays to identify rearrangement partners. Previous work in Burkitt lymphoma has classified MYC translocations according to recurrent breakpoint patterns, with breaks located in the MYC gene (class I), immediately upstream (class II), distally upstream (class III), or downstream.18 The patterns and relative incidences of these classes in lymphomas with DLBCL morphology have not been examined on a large scale. Currently, it remains unclear whether the location of the MYC break has any significance and whether breakpoint architecture differs between patient subsets (eg, HGBL-DH). Published studies have produced conflicting evidence about whether MYC rearrangement partner impacts patient outcome, with some demonstrating that MYC immunoglobulin (IG) rearrangements are associated with inferior survival compared with MYC–non-IG rearrangements and other studies showing no association.12-14,19,20 However, the relationship among breakpoint location, MYC partner, and outcome has never been examined. Furthermore, some of these studies have used FISH break-apart assays with narrow gap sizes that have been demonstrated to lack the ability to detect a proportion of MYC locus rearrangements “(2756, 1st column). Chong teaches, “Many of the MYC breakpoints (35/105; 33%) occur in a cluster in close proximity to the MYC coding sequence, which we define here as the “genic cluster,” spanning from ;1.5 kb upstream of the transcription start site to the end of MYC intron 1 (;3.7 kb total). This cluster encompasses the class I and class II MYC translocations previously defined in Burkitt lymphoma.18 The remaining breakpoints are located outside the gene region, with 27% (19/70) occurring upstream of MYC in a space that includes previously defined class III MYC translocations.18 However, the majority of nongenic rearrangements occur telomeric to the genic cluster (51/70; 73%) up to 0.6 Mb downstream of MYC.” (page 2758, 2nd column, 2nd paragraph). Chong teaches, “We identified a genic cluster of MYC breakpoints located near the end of the coding sequence, which is highly enriched for MYC-IGH rearrangements, and demonstrated that most nongenic MYC rearrangements have non-IG partners and occur downstream of the gene. All downstream breakpoints identified are located within a region ;565 kb telomeric of the coding space, which has been demonstrated to be enriched for enhancer elements.” (page 2761, 2nd column).
While Chong teaches an IGH-myc breakpoint translocation, Chong does not specifically teach treating based on MYC.
However, Li teaches, “Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma in the USA. Based on gene expression profiling (GEP) studies, DLBCL can be classified into germinal center B cell (GCB) and activated B cell (ABC) subtypes. In addition to the cell of origin, genetic studies have identified a prognostic role for MYC rearrangements in DLBCL. Earlier studies reported that 5–15% of DLBCL harbored MYC, BLC2, and/or BCL6 translocations and were called “double-hit” lymphoma (DHL) or triple-hit lymphoma (THL).” Li teaches, “In summary, our findings provide a rationale for using BET bromodomain inhibitors alone or in combination with BCL-2-specific inhibitors as the first-line therapy option for double-hit and triple-hit patients. This study demonstrates that, apparently, there is no distinctive feature of DHL/THL lymphoma with respect to sensitivity to BET inhibitors, and MYC-expressing lymphoma cells are probably addicted to the MYC-oncogenic effect and rely on MYC for their growth regardless of MYC rearrangements. Moreover, our study emphasizes on incorporation of FISH analysis along with MYC expression into the standard diagnostic procedure for prompt and accurate identification of DHL and THL patients to start the BET inhibitor therapy alone or in combination with other therapeutic drugs to improve the outcome.” (page 12, bottom of 1st column, top of 2nd column).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to treat DLBCL patients with IGh-Myc rearrangement within 1.6 MB of the transcription start site. The artisan would be motivated as Li teaches, “Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma in the USA” and “our findings provide a rationale for using BET bromodomain inhibitors alone or in combination with BCL-2-specific inhibitors as the first-line therapy option for double-hit and triple-hit patients. This study demonstrates that, apparently, there is no distinctive feature of DHL/THL lymphoma with respect to sensitivity to BET inhibitors, and MYC-expressing lymphoma cells are probably addicted to the MYC-oncogenic effect and rely on MYC for their growth regardless of MYC rearrangements.” The artisan would have a reasonable expectation of success as the artisan is merely using a known treatment for a known cancer with a known IGH-MYC translocation.
With regards to claim 19, 25-26 Li teaches, “Beti interfere with MYC transcription by physically blocking binding of BRD proteins at regulatory elements that influence MYC expression.” (page 6, 2nd column).
With regards to claim 29, LI and Chong teach MYC.
With regards to claim 30, Li and Chon teach DLBCL.
With regards to claims 31, LI teaches DLBCL and MYC.
With regards to claim 38, Li teaches MYC is overexpressed. Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims overexpression encompasses a 2 fold expression over a reference.
With regards to claim 50, 52LI and Chong teach detection of translocation in DNA.
With regards to claims 57, Chong teaches enhancer regions (figure 5)
With regards to claim 58, Chong and Li teach humans
Summary
No claims are allowed.
Conclusion
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/Steven Pohnert/Primary Examiner, Art Unit 1683
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