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 and the species elections of (i) ANLN, ESR1, PGR, & SLC39A6 and (ii) SFRS1, DNAJC6, FBXO5, DCK, & TMPO in claims 1, 3, 5, 14, & 31, of 8 housekeeping genes of ACTB, MRPL19, PSMC4, RPLP0, SF3A1, GUSB, PUM1, & TFRC in claim 7, of all (i)-(iv) in claim 31, and of abemaciclib in claim 41 in the reply filed on 10/28/2025 is acknowledged. Group II, claim 33, is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A first office action on the merits of claims 1-14, 26, 30, 31, 40, & 41 is set forth herein and claim 33 is withdrawn from consideration.
Information Disclosure Statement
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 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 1-14, 26, 30, 31, 40, & 41 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.
Regarding claim 1, the claim recites the limitations “the gene expression” in line 4, “the patient” in line 4, “the breast tumor” in line 5, and “the subject” in line 19 of the claim and there is insufficient antecedent basis for these limitations in the claim. In addition, the recitations of “the patient” in line 4 and of “the subject” in line 19 of the claim is unclear if both recitations are referring to “a human subject” in line 1 of the claim or if “a human subject”, “the patient”, or “the subject” are referring to different individuals. In addition, the recitation of “making a predication of whether the subject will be resistant to or sensitive to said CDK inhibitor treatment based on the sample gene expression profile comprising said module (i) to (iv)” in lines 19-21 of the claim is unclear. It is unclear what the relationship is between resistance and sensitivity to CDK inhibitor treatment and the expression of genes from modules (i)-(iv). Does overexpression or underexpression of particular genes predict resistance to CDK inhibitors? Sensitivity to CDK inhibitors? In addition, the recitation of “…TYMS, UBE2C and UBE2T” in line 12 of the claim is unclear if UBE2C and UBE2T are a part of the same luminal vs. non-luminal module gene, or if this is the result of a typographical error and should read “…TYMS, UBE2C, and UBE2T”. In addition, the recitation of “…SNRPD1, STMN1 and TMPO” in line 16 of the claim is unclear if STMN1 and TMPO are a part of the same E2F module gene, or if this is the result of a typographical error and should read “…SNRPD1, STMN1, and TMPO”.
Regarding claim 2, the recitation of “…ESR1, PGR and SLC39A6” in line 2 of the claim is unclear if PGR and SLC39A6 are a part of the same luminal vs. non-luminal module gene, or if this is the result of a typographical error and should read “…ESR1, PGR, and SLC39A6”.
Regarding claim 3, the recitation of “…TYMS, UBE2C and UBE2T” in line 6 of the claim is unclear if UBE2C and UBE2T are a part of the same luminal vs. non-luminal module gene, or if this is the result of a typographical error and should read “…TYMS, UBE2C, and UBE2T”.
Regarding claim 5, the recitation of “…SNRPD1, STMN1 and TMPO” in line 4 of the claim is unclear if STMN1 and TMPO are a part of the same E2F module gene, or if this is the result of a typographical error and should read “…SNRPD1, STMN1, and TMPO”.
Regarding claim 6, the claim recites the limitation “the gene expression” in line 2 of the claim and there is insufficient antecedent basis for this limitation in the claim. In addition, it is unclear if “the gene expression in the sample of one or more housekeeping genes” refers back to the same gene expression measured in modules (i)-(iv) in claim 1, from which claim 6 depends from.
Regarding claim 7, the recitation of “…GUSB (alias GUS), PUM1 and TFRC” in line 3 of the claim is unclear if PUM1 and TFRC are a part of the same housekeeping gene, or if this is the result of a typographical error and should read “…GUSB (alias GUS), PUM1, and TFRC”.
Regarding claim 8, the claim recites the limitation of “the subject” in lines 1-2 & 8 of the claim and it is unclear and there is insufficient antecedent basis for this limitation in the claim. It is unclear if “the subject” is referring to “a human subject” in line 1 of claim 1, from which claim 8 depends from, or if “the subject” if referring to a different individual than “a human subject”. In addition, the recitation of “the E2F module classifies the sample as having high E2F expression” in line 5 of the claim is unclear. It is unclear what is encompassed by “having high E2F expression” when the E2F module requires measuring the expression of at least five genes. Do each of the at least five genes measured in the E2F module require high expression or are only some of the at least five genes require high expression to classify the sample as having high E2F expression? If the latter, then how is it determined which genes of the at least five genes require high expression?
Regarding claim 9, the claim recites the limitation of “the subject” in line 6 of the claim and it is unclear and there is insufficient antecedent basis for this limitation in the claim. It is unclear if “the subject” is referring to “a human subject” in line 1 of claim 1, from which claim 9 depends from, or if “the subject” if referring to a different individual than “a human subject”. In addition, the recitation of “the E2F module classifies the sample as having low E2F expression” in line 3 of the claim is unclear. It is unclear what is encompassed by “having low E2F expression” when the E2F module requires measuring the expression of at least five genes. Do each of the at least five genes measured in the E2F module require low expression or are only some of the at least five genes require low expression to classify the sample as having low E2F expression? If the latter, then how is it determined which genes of the at least five genes require low expression?
Regarding claim 10, the recitation of “when the average log2 gene expression of E2F signature genes is greater than or equal to 9.392 or is greater than or equal to 9.4462” in lines 2-3 of the claim is unclear how this value is calculated and how to determine what expression levels of the elected genes are encompassed by this recitation.
Regarding claim 11, the recitation of “when the average log2 gene expression measures less than or equal to 8.4068 or measures less than or equal to 8.4332” in lines 2-3 of the claim is unclear how this value is calculated and how to determine what expression levels of the RB1 gene are encompassed by this recitation.
Regarding claim 12, the recitation of “when the average log2 gene expression measures greater than or equal to 8.264 or measures greater than or equal to 7.9596” in lines 2-3 of the claim is unclear how this value is calculated and how to determine what expression levels of the CCN1E gene are encompassed by this recitation. In addition, the claim recites the limitations of “the CCN1E module” and “having high CCN1E expression” in lines 1-2 of the claim and it is unclear and there is insufficient antecedent basis for these limitations in the claim. It is unclear the “the CCN1E module” and “CCNE1 expression” is a typographical error and is referring back to “a CCNE1 module” in claim 1, from which claim depends from, or is referring to measuring expression of a different gene than CCNE1.
Regarding claim 13, the recitation of “classifies the sample as luminal or non-luminal on the basis of the nearest centroid” in lines 2-3 of the claim is unclear what the relationship is between the nearest centroid and the sample being luminal or non-luminal? How does the nearest centroid classify a sample as luminal or non-luminal? In addition, the claim recites the limitations of “the genes of said luminal vs. non-luminal module” in lines 3-4 of the claim and of “the said genes” in line 5 of the claim and it is unclear and there is insufficient antecedent basis for these limitations in the claim. It is unclear if these limitations are referring to the “at least four genes” as recited in claim 1, from which claim 13 depends from, or if “the genes” and the “said genes” encompasses additional genes not selected for the group of at least four genes.
Regarding claim 14, the claim recites the limitations of “the genes of the luminal vs. non-luminal module” in lines 1-2 of the claim and it is unclear and there is insufficient antecedent basis for these limitations in the claim. It is unclear if these limitations are referring to the “at least four genes” as recited in claim 1, from which claim 14 depends from, or if “the genes” encompasses additional genes not selected for the group of at least four genes. In addition, the recitation of “selected from the following a) to f)” referring to a table is indefinite. As stated in MPEP 2173.05(s), the claims should be complete to themselves and the reference to a table in the specification renders the claim incomplete. Claims which recited tables are only permitted in exceptional circumstances where there is not practical way to define the invention in words or where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. In addition, it is unclear what are the purpose of the headings in the table? In addition, what do the values mean and how are the used in the luminal vs. non-luminal module?
Regarding claim 26, the claim recites the limitation of “the subject” in lines 1-2 of the claim and it is unclear and there is insufficient antecedent basis for this limitation in the claim. It is unclear if “the subject” is referring to “a human subject” in line 1 of claim 1, from which claim 26 depends from, or if “the subject” if referring to a different individual than “a human subject”.
Regarding claim 30, the claim recites the limitation of “the subject” in line 1 of the claim and it is unclear and there is insufficient antecedent basis for this limitation in the claim. It is unclear if “the subject” is referring to “a human subject” in line 1 of claim 1, from which claim 30 depends from, or if “the subject” if referring to a different individual than “a human subject”.
Regarding claim 31, the claim recites the limitations “the gene expression” in line 4, “the breast tumor” in line 5, and “the subject” in lines 5, 23, & 29 of the claim and there is insufficient antecedent basis for these limitations in the claim. In addition, the recitation of “the subject” in lines 5, 23, & 29 of the claim is unclear if both recitations are referring to “a human subject” in line 1 of the claim or if “a human subject” and “the subject” are referring to different individuals. In addition, the recitation of “the E2F module classifies the sample as having high E2F expression” in line 26 of the claim is unclear. It is unclear what is encompassed by “having high E2F expression” when the E2F module requires measuring the expression of at least five genes. Do each of the at least five genes measured in the E2F module require high expression or are only some of the at least five genes require high expression to classify the sample as having high E2F expression? If the latter, then how is it determined which genes of the at least five genes require high expression? In addition, the recitation of “…TYMS, UBE2C and UBE2T” in line 12 of the claim is unclear if UBE2C and UBE2T are a part of the same luminal vs. non-luminal module gene, or if this is the result of a typographical error and should read “…TYMS, UBE2C, and UBE2T”. In addition, the recitation of “…SNRPD1, STMN1 and TMPO” in line 16 of the claim is unclear if STMN1 and TMPO are a part of the same E2F module gene, or if this is the result of a typographical error and should read “…SNRPD1, STMN1, and TMPO”.
Regarding claim 40, the claim recites the limitation of “the subject” in line 1 of the claim and it is unclear and there is insufficient antecedent basis for this limitation in the claim. It is unclear if “the subject” is referring to “a human subject” in line 1 of claim 1, from which claim 40 depends from, or if “the subject” if referring to a different individual than “a human subject”.
Regarding claim 41, the claim recites the limitation of “the subject” in line 1 of the claim and it is unclear and there is insufficient antecedent basis for this limitation in the claim. It is unclear if “the subject” is referring to “a human subject” in line 1 of claim 1, from which claim 41 depends from, or if “the subject” if referring to a different individual than “a human subject”. In addition, the recitation of “selected from: palbociclib, abemaciclib and ribociclib” in line 2 of the claim is unclear if abemaciclib and ribociclib are a part of the same CDK4/6 inhibitor, or if this is the result of a typographical error and should read “selected from: palbociclib, abemaciclib, and ribociclib”.
Claim 4 is rejected due to its dependence on claim 1.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-5, 8-14, 26, 31, 40, & 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garrido-Castro (Garrido-Castro & Goel; Curr Breast Cancer Rep, Vol. 9, pages 26-33, February 2017), as cited in the IDS dated 03/24/2023, in view of Miller (Miller et al.; Cancer Discover, Vol. 1, pages 338-351, September 2011), as cited in the IDS dated 03/24/2023, as evidenced by Parker (Parker et al.; Journal of Clinical Oncology Vol. 27, pages 1160-1167, February 2009), as cited on the IDS dated 10/24/2023.
Regarding claim 1, it is noted that the specification of the instant application teaches that the luminal vs. non-luminal classification may be made according to the PAM50 nearest centroid as disclosed in Parker (Parker et al., J Clin Oncol, 2009, Vol. 27, pages 1160-1167) (paragraph [37] of the instant specification).
Garrido-Castro teaches a method for determining potential biomarkers for sensitivity or resistance to CDK4/6 inhibitors in which the biomarkers comprise measuring a luminal pattern of gene expression as assessed by the PAM50 gene set (abstract purpose of review lines 1-5; pg. 30 1st column 1st full paragraph lines 1-12), in which the PAM50 gene set encompasses the genes of ANLN, ESRL, PGR, and SLC39A6, as evidenced by Parker (abstract purpose lines 1-3; pg. 1164-1165 paragraph bridging pg. 1164 & 1165 lines 1-12; pg. 1166 column 1 1st full paragraph lines 1-6; Supplemental Table 5 of Parker), (measuring gene expression of a luminal vs. non-luminal module comprising at least four genes of ANLN, ESR1, PGR, & SLC39A6), measuring E2F transcription factor activity and expression of E2F target genes (measuring gene expression of a E2F module), measuring expression of RB1 (measuring gene expression of a RB1 module), and measuring expression of CCNE1 (measuring gene expression of CCNE1 module) to predict resistance or sensitivity to CDK4/6 inhibitors in patients with breast cancer (making a prediction of whether the subject will be resistant or sensitive to CDK inhibitor treated based on the sample gene expression profiles of modules (i)-(iv)) (abstract summary lines 1-6; pg. 27 column 2 1st full paragraph lines 13-20; pg. 28 column 2 1st full paragraph lines 9-13; pg. 30 column 2 3rd full paragraph lines 1-18; pg. 31 column 1 2nd full paragraph lines 1-11).
Garrido-Castro does not teach that the E2F module comprises measuring the gene expression of DCK, DNAJC9, FBXO5, SFRS1, and TMPO genes.
Miller teaches a E2F activation gene signature that correlates with a lesser response to treatment in breast cancer patients in which this E2F gene signature comprises measuring the expression of DCK, DNAJC9, FBXO5, SFRS1, and TMPO genes (E2F module comprising at least five genes of DCK, DNAJC9, FBXO5, SFRS1, and TMPO) (abstract lines 1-15; pg. 343 column 2 1st full paragraph lines 1-12; Fig. S7B). In addition, Miller teaches that this method is important is supporting further development of ER downregulators and CDK4 inhibitors for the treatment of antiestrogen-resistant breast cancers (abstract significance lines 1-6).
Garrido-Castro and Miller are considered to be analogous to the claimed invention because they are all in the same field of determining response to treatment in breast cancer patients with expression of E2F genes. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of measuring E2F transcription factor activity and expression of E2F target genes to determine resistance or sensitivity to CDK4/6 inhibitors in breast cancer patients in Garrido-Castro to incorporate measuring an E2F gene signature comprising the expression of DCK, DNAJC9, FBXO5, SFRS1, and TMPO as taught in Miller because Miller teaches that doing so would provide a method that is important in supporting further development of CDK4 inhibitors for the treatment of antiestrogen-resistant breast cancer.
Regarding claim 2, Garrido-Castro teaches measuring a luminal pattern of gene expression as assessed by the PAM50 gene set (pg. 30 1st column 1st full paragraph lines 1-12), in which the PAM50 gene set encompasses the genes of ANLN, ESRL, PGR, and SLC39A6, as evidenced by Parker (abstract purpose lines 1-3; pg. 1164-1165 paragraph bridging pg. 1164 & 1165 lines 1-12; pg. 1166 column 1 1st full paragraph lines 1-6; Supplemental Table 5 of Parker), (measuring gene expression of a luminal vs. non-luminal module comprising genes of ANLN, ESR1, PGR, & SLC39A6).
Regarding claim 3, Garrido-Castro teaches measuring a luminal pattern of gene expression as assessed by the PAM50 gene set (pg. 30 1st column 1st full paragraph lines 1-12), in which the PAM50 gene set encompasses the all of the genes listed in claim 3, as evidenced by Parker (abstract purpose lines 1-3; pg. 1164-1165 paragraph bridging pg. 1164 & 1165 lines 1-12; pg. 1166 column 1 1st full paragraph lines 1-6; Supplemental Table 5 of Parker), (measuring gene expression of a luminal vs. non-luminal module comprising genes of claim 3 lines 2-6).
Regarding claim 4, Miller teaches measuring a E2F activation gene signature in which this E2F gene signature comprises measuring the expression of DCK, DNAJC9, FBXO5, SFRS1, and TMPO genes (E2F module comprising at least five genes of DCK, DNAJC9, FBXO5, SFRS1, and TMPO) (abstract lines 1-15; pg. 343 column 2 1st full paragraph lines 1-12; Fig. S7B).
Regarding claim 5, Miller teaches measuring a E2F activation gene signature in which this E2F gene signature comprises measuring the expression of all of the genes listed in claim 5 (E2F module comprising genes of claim 5 lines 2-4) (abstract lines 1-15; pg. 343 column 2 1st full paragraph lines 1-12; Fig. S7B).
Regarding claim 8, Garrido-Castro teaches that breast cancer with a luminal gene expression pattern might show sensitivity to CDK4/6 inhibitors (resistant to CDK inhibitor if the sample is classified as non-luminal), unconstrained E2F transcription factor activity (high E2F expression) classifies a sample as resistant to CDK4/6 inhibitors (resistant to CDK inhibitor if sample is classified as having high E2F expression), loss of RB1 classifies the sample as resistant to CDK4/6 inhibitors (resistant to CDK inhibitor if sample is classified as having low RB1 expression), and hyperactivity of CCNE1 (high CCNE1 expression) classifies the sample as resistant to CDK4/6 inhibitors (resistant to CDK inhibitors if sample is classified as having high CCNE1 expression) (pg. 30 1st column 1st full paragraph lines 1-12; pg. 30 column 2 3rd full paragraph lines 1-18; pg. 31 column 1 2nd full paragraph lines 1-11).
Regarding claim 9, Garrido-Castro teaches that breast cancer with a luminal gene expression pattern might show sensitivity to CDK4/6 inhibitors (sensitive to CDK inhibitor if the sample is classified as luminal), unconstrained E2F transcription factor activity (high E2F expression) classifies a sample as resistant to CDK4/6 inhibitors (sensitive to CDK inhibitor if sample is classified as having low E2F expression), loss of RB1 classifies the sample as resistant to CDK4/6 inhibitors (sensitive to CDK inhibitor if sample is classified as having high RB1 expression), and hyperactivity of CCNE1 (high CCNE1 expression) classifies the sample as resistant to CDK4/6 inhibitors (sensitive to CDK inhibitors if sample is classified as having low CCNE1 expression) (pg. 30 1st column 1st full paragraph lines 1-12; pg. 30 column 2 3rd full paragraph lines 1-18; pg. 31 column 1 2nd full paragraph lines 1-11).
Regarding claim 10, as discussed above , the recitation of “when the average log2 gene expression of E2F signature genes is greater than or equal to 9.392 or is greater than or equal to 9.4462” in lines 2-3 of the claim is unclear how this value is calculated and how to determine what expression levels of the elected genes are encompassed by this recitation. Further, the claim does not define how to calculate these average log2 gene expression values. Garrido-Castro teaches measuring E2F transcription factor activity and expression of E2F target genes (measuring gene expression of a E2F module). Therefore, the average log2 gene expression is taken to be inherent to the genes themselves (average log2 gene expression of E2F signature genes is greater than or equal to 9.392 or is greater than or equal to 9.4462) (pg. 30 column 2 3rd full paragraph lines 1-18).
Regarding claim 11, as discussed above, the recitation of “when the average log2 gene expression measures less than or equal to 8.4068 or measures less than or equal to 8.4332” in lines 2-3 of the claim is unclear how this value is calculated and how to determine what expression levels of the RB1 gene are encompassed by this recitation. Further, the claim does not define how to calculi these average log2 gene expression values. Garrido-Castro teaches measuring expression of RB1 (measuring gene expression of a RB1 module). Therefore, the average log2 gene expression is taken to be inherent to the genes themselves (average log2 gene expression measures less than or equal to 8.4068 or measures less than or equal to 8.4332) (pg. 30 column 2 3rd full paragraph lines 1-18).
Regarding claim 12, as discussed above, the recitation of “when the average log2 gene expression measures greater than or equal to 8.264 or measures greater than or equal to 7.9596” in lines 2-3 of the claim is unclear how this value is calculated and how to determine what expression levels of the CCN1E gene are encompassed by this recitation. Further, the claim does not define how to calculi these average log2 gene expression values. Garrido-Castro teaches measuring expression of CCNE1 (measuring gene expression of CCNE1 module). Therefore, the average log2 gene expression is taken to be inherent to the genes themselves (average log2 gene expression measures greater than or equal to 8.264 or measures greater than or equal to 7.9596) (pg. 31 column 1 2nd full paragraph lines 1-11).
Regarding claim 13, it is noted that the specification of the instant application teaches that the luminal vs. non-luminal classification may be made according to the PAM50 nearest centroid as disclosed in Parker (Parker et al., J Clin Oncol, 2009, Vol. 27, pages 1160-1167) (paragraph [37] of the instant specification).
Garrido-Castro teaches measuring a luminal pattern of gene expression as assessed by the PAM50 gene set (abstract purpose of review lines 1-5; pg. 30 1st column 1st full paragraph lines 1-12), in which the PAM50 gene set encompasses centroid-based prediction methods comprising classifying the sample on classification of the nearest centroid (the luminal vs. non-luminal module classifies the sample as luminal vs. non-luminal on the basis of the nearest centroid), as evidenced by Parker (abstract purpose lines 1-3; pg. 1161 column 2 5th full paragraph lines 1-9; pg. 1164-1165 paragraph bridging pg. 1164 & 1165 lines 1-12; pg. 1166 column 1 1st full paragraph lines 1-6; Supplemental Table 5 of Parker).
Regarding claim 14, as discussed above the recitation of “selected from the following a) to f)” referring to a table is indefinite. As stated in MPEP 2173.05(s), the claims should be complete to themselves and the reference to a table in the specification renders the claim incomplete. Claims which recited tables are only permitted in exceptional circumstances where there is not practical way to define the invention in words or where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. In addition, it is unclear what are the purpose of the headings in the table? In addition, what do the values mean and how are the used in the luminal vs. non-luminal module? Therefore, for the purposes of this rejection it is interpreted that claim 14 require measuring the expression of the elected genes of ANLN, ESR1, PGR, and SLC39A6 (a) for classifying a sample as luminal vs. non-luminal.
Garrido-Castro teaches measuring a luminal pattern of gene expression as assessed by the PAM50 gene set (pg. 30 1st column 1st full paragraph lines 1-12), in which the PAM50 gene set encompasses the genes of ANLN, ESRL, PGR, and SLC39A6, as evidenced by Parker (abstract purpose lines 1-3; pg. 1164-1165 paragraph bridging pg. 1164 & 1165 lines 1-12; pg. 1166 column 1 1st full paragraph lines 1-6; Supplemental Table 5 of Parker), (measuring gene expression of a luminal vs. non-luminal module of (a) comprising genes of ANLN, ESR1, PGR, & SLC39A6).
Regarding claim 26, Garrido-Castro teaches a method for determining potential biomarkers for sensitivity or resistance to CDK4/6 inhibitors in which determining sensitivity to CDK4/6 inhibitors identifies useful clinical markers for potential candidates for CDK4/6 inhibitor therapy (administering a therapeutically effective amount of a CDK inhibitor if subject is predicted to be sensitive to CDK inhibitor therapy) (pg. 29-30 paragraph bridging pg. 29 & pg. 30 lines 20-25).
Regarding claim 31, it is noted that the specification of the instant application teaches that the luminal vs. non-luminal classification may be made according to the PAM50 nearest centroid as disclosed in Parker (Parker et al., J Clin Oncol, 2009, Vol. 27, pages 1160-1167) (paragraph [37] of the instant specification).
Garrido-Castro teaches a method for determining potential biomarkers for sensitivity or resistance to CDK4/6 inhibitors in which the biomarkers comprise measuring a luminal pattern of gene expression as assessed by the PAM50 gene set (abstract purpose of review lines 1-5; pg. 30 1st column 1st full paragraph lines 1-12), in which the PAM50 gene set encompasses the genes of ANLN, ESRL, PGR, and SLC39A6, as evidenced by Parker (abstract purpose lines 1-3; pg. 1164-1165 paragraph bridging pg. 1164 & 1165 lines 1-12; pg. 1166 column 1 1st full paragraph lines 1-6; Supplemental Table 5 of Parker), (measuring gene expression of a luminal vs. non-luminal module comprising at least four genes of ANLN, ESR1, PGR, & SLC39A6), measuring E2F transcription factor activity and expression of E2F target genes (measuring gene expression of a E2F module), measuring expression of RB1 (measuring gene expression of a RB1 module), and measuring expression of CCNE1 (measuring gene expression of CCNE1 module) to predict resistance or sensitivity to CDK4/6 inhibitors in patients with breast cancer (making a prediction of whether the subject will be resistant or sensitive to CDK inhibitor treated based on the sample gene expression profiles of modules (i)-(iv)) (abstract summary lines 1-6; pg. 27 column 2 1st full paragraph lines 13-20; pg. 28 column 2 1st full paragraph lines 9-13; pg. 30 column 2 3rd full paragraph lines 1-18; pg. 31 column 1 2nd full paragraph lines 1-11). Garrido-Castro also teaches that breast cancer with a luminal gene expression pattern might show sensitivity to CDK4/6 inhibitors (resistant to CDK inhibitor if the sample is classified as non-luminal), unconstrained E2F transcription factor activity (high E2F expression) classifies a sample as resistant to CDK4/6 inhibitors (resistant to CDK inhibitor if sample is classified as having high E2F expression), loss of RB1 classifies the sample as resistant to CDK4/6 inhibitors (resistant to CDK inhibitor if sample is classified as having low RB1 expression), and hyperactivity of CCNE1 (high CCNE1 expression) classifies the sample as resistant to CDK4/6 inhibitors (resistant to CDK inhibitors if sample is classified as having high CCNE1 expression) (pg. 30 1st column 1st full paragraph lines 1-12; pg. 30 column 2 3rd full paragraph lines 1-18; pg. 31 column 1 2nd full paragraph lines 1-11).
Garrido-Castro does not teach that the E2F module comprises measuring the gene expression of DCK, DNAJC9, FBXO5, SFRS1, and TMPO genes.
Miller teaches a E2F activation gene signature that correlates with a lesser response to treatment in breast cancer patients in which this E2F gene signature comprises measuring the expression of DCK, DNAJC9, FBXO5, SFRS1, and TMPO genes (E2F module comprising at least five genes of DCK, DNAJC9, FBXO5, SFRS1, and TMPO) (abstract lines 1-15; pg. 343 column 2 1st full paragraph lines 1-12; Fig. S7B). In addition, Miller teaches that this method is important is supporting further development of ER downregulators and CDK4 inhibitors for the treatment of antiestrogen-resistant breast cancers (abstract significance lines 1-6).
Garrido-Castro and Miller are considered to be analogous to the claimed invention because they are all in the same field of determining response to treatment in breast cancer patients with expression of E2F genes. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of measuring E2F transcription factor activity and expression of E2F target genes to determine resistance or sensitivity to CDK4/6 inhibitors in breast cancer patients in Garrido-Castro to incorporate measuring an E2F gene signature comprising the expression of DCK, DNAJC9, FBXO5, SFRS1, and TMPO as taught in Miller because Miller teaches that doing so would provide a method that is important in supporting further development of CDK4 inhibitors for the treatment of antiestrogen-resistant breast cancer.
Regarding claims 40 & 41, Garrido-Castro teaches CDK4/6 inhibitors including abemaciclib (CDK inhibitor administered to the subject is CDK4/6 inhibitor of abemaciclib) (pg. 26-27 paragraph bridging pg. 26 & pg. 27 lines 1-17; pg. 29-30 paragraph bridging pg. 29 & pg. 30 lines 20-25).
Claim(s) 6 & 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garrido-Castro (Garrido-Castro & Goel; Curr Breast Cancer Rep, Vol. 9, pages 26-33, February 2017), as cited in the IDS dated 03/24/2023, and Miller (Miller et al.; Cancer Discover, Vol. 1, pages 338-351, September 2011), as cited in the IDS dated 03/24/2023, as evidenced by Parker (Parker et al.; Journal of Clinical Oncology Vol. 27, pages 1160-1167, February 2009), as cited on the IDS dated 10/24/2023 as applied to claims 1-5, 8, 9, 13, 14, 26, 31, 40, & 41 above, and further in view of Perou (United States Patent Application Publication US 2019/0264290 A1).
The teachings of Garrido-Castro and Miller with respect to claim 1 is discussed above.
Regarding claims 6 & 7, Garrido-Castro & Miller does not teach measuring the expression of at least 8 housekeeping genes.
Perou teaches a method of predicting outcome or response to therapy of a subject diagnosed with or suspected of having breast cancer through measuring a gene expression profile comprising normalizing gene expression values to a set of housekeeping genes comprising ACTB, MRPL19, PSMC4, RPLP0, SF3A1, GUSB, PUM1, and TFRC (measuring the gene expression of at least 8 housekeeping genes comprising ACTB, MRPL19, PSMC4, RPLP0, SF3A1, GUSB, PUM1, and TFRC) (abstract lines 1-18; pg. 53 claim 6 lines 1-2; pg. 53 claim 7 lines 1-3). In addition, Perou teaches that expression profiling of breast cancer is important in identifying biologically and clinically different molecular subtypes that may require different treatment approaches (paragraph [0022] lines 1-3).
Garrido-Castro, Miller, and Perou are considered to be analogous to the claimed invention because they are all in the same field of measuring expression of genes in breast cancer patients to asses response to therapy. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of measuring a gene expression profile comprising modules (i)-(iv) to determine resistance or sensitivity to CDK4/6 inhibitors in breast cancer patients in Garrido-Castro to incorporate measuring a set of housekeeping genes comprising ACTB, MRPL19, PSMC4, RPLP0, SF3A1, GUSB, PUM1, and TFRC as taught in Perou because Perou teaches that doing so would provide a method that is important in identifying biologically and clinically different molecular subtypes that may require different treatment approaches.
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garrido-Castro (Garrido-Castro & Goel; Curr Breast Cancer Rep, Vol. 9, pages 26-33, February 2017), as cited in the IDS dated 03/24/2023, and Miller (Miller et al.; Cancer Discover, Vol. 1, pages 338-351, September 2011), as cited in the IDS dated 03/24/2023, as evidenced by Parker (Parker et al.; Journal of Clinical Oncology Vol. 27, pages 1160-1167, February 2009), as cited on the IDS dated 10/24/2023 as applied to claims 1-5, 8, 9, 13, 14, 26, 31, 40, & 41 above, and further in view of Buzdar (Buzdar; Semin Oncol, Vol. 28, pages 291-304, June 2001).
The teachings of Garrido-Castro and Miller with respect to claim 1 is discussed above.
Regarding claim 30, Garrido-Castro teaches administering a combination of CDK4/6 inhibitors with endocrine therapy when predicting resistance or sensitivity to CDK4/6 inhibitors (pg. 29 column 1 1st full paragraph lines 1-6; pg. 31 column 2 2nd full paragraph lines 1-5).
Garrido-Castro & Miller does not teach administering endocrine therapy in the absence of any CDK4/6 inhibitor.
Buzdar teaches a method of administering treating patients with breast cancer with endocrine therapy (abstract lines 1-10; pg. 292 column 2 2nd full paragraph lines 1-6). In addition, Buzdar teaches endocrine therapy offers an effective treatment in breast cancer patients (pg. 301 column 2 1st full paragraph lines 1-2).
Garrido-Castro, Miller, and Buzdar are considered to be analogous to the claimed invention because they are all in the same field of assessing response to therapy in breast cancer patients. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of measuring a gene expression profile comprising modules (i)-(iv) to determine resistance or sensitivity to CDK4/6 inhibitors in breast cancer patients and administering a combination of CDK4/6 inhibitors with endocrine therapy when predicting resistance to CDK4/6 inhibitors in Garrido-Castro to incorporate administering endocrine therapy in the absence of a CDK4/6 inhibitor as taught in Buzdar because Buzdar teaches that doing so would provide an effective treatment in patients with breast cancer.
Conclusion
Claims 1-14, 26, 30, 31, 40, & 41 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682