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
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 33-38, 44-48, and 50-52, drawn to a method of predicting breast cancer by calculating a probability with biomarker expression, classified in class 702, subclass 19.
II. Claims 39-43 and 49, drawn to a kit comprising probes for measuring transcriptome markers and probes and/or detection reagents for measuring expression level cell surface biomarkers, classified in class 702, subclass 19.
The inventions are distinct, each from the other because of the following reasons:
Inventions of Group I and Group II are directed to related processes and systems of detecting breast cancer. The related inventions are distinct if the (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the process of Group I is biomarker quantity calculation method of calculating probability based on amounts of the biomarkers. In contrast, Group II is to a kit comprising physical probes and reagents for measuring the claimed biomarkers. Therefore, the methods set forth in Groups I and II have a materially different design, functions, or effects. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants.
Restriction for examination purposes as indicated is proper because all these inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and examination burden if restriction were not required because one or more of the following reasons apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
(d) the prior art applicable to one invention would not likely be applicable to another invention;
(e) the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected invention. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other invention.
Interview Summary
Examiner contacted Applicant’s representative on 9 July 2026 at Oliff PLC, Tiffany Adigwe, to request the above set forth restriction/election by telephone. Applicants declined and requested the restriction in writing. Examiner has examined both separate inventions.
Information Disclosure Statement
The IDS filed 7/19/2023 have been considered by the Examiner.
Priority
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to EP21151781.8 filed 1/15/2021.
Status of Claims
Claims 1-32 are cancelled.
Claims 33-52 are new and under examination.
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 33-52 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 33-38, 44-48 and 50-52 are drawn to a method, so a process.
Claims 39-43 and 49 are drawn to a kit of probes, so a product.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s)
1. Calculating a probability score based on the measurement of step (a) which is drawn to measuring expression level of mRNA markers of SOX4, TNFSF20, CD3G and NR3C2 and CD11b, CD62L, CD86, CD117, CD144, CD177 and CD202b .
The step reads on a process that can be performed by the human mind or with math and is therefore an abstract idea.
2. Ruling out breast cancer for the female subject if the score is lower than a pre-determined score or ruling in likelihood of breast cancer for the female subject if the score is higher than a predetermined score.
These steps of ruling in or ruling out breast cancer are decision making steps that can be performed by the human mind by comparing numerical score values. The seps are therefore drawn to an abstract idea.
3. in which the probability score is P is calculated by the formula recited in claim 1.
This limitation sets for an equation to be calculated, which is math and therefore an abstract idea.
4. wherein a probability score Py closer to 1 represents likelihood of breast cancer and a probability score Py closer to 0 represents likelihood of no breast cancer.
This limitation requires evaluating a numerical score which can be performed by the human mind and is therefore an abstract idea.
Dependent claim 38 is drawn to describing the calculation of the probability score and is also an abstract idea.
Dependent claims 34-38, 44-48 and 51-52 are further drawn to additional marker genes and proteins in the calculation steps and evaluation of the breast cancer prediction, and are therefore also an abstract idea.
Step 2A Prong One: Identification of an Natural Product
Claims 39-43 and 49 are drawn to 1) probes for measuring mRNA expression of a panel of genes and 2) probes or detection reagents for measuring expression level of cell surface CD biomarkers. The claimed probes and detection reagents read on natural products.
1. Regarding the probes for measuring mRNA expression, their structures are not further defined in the claims and read on any polynucleotide capable of measuring the expression level of the named genes. See MPEP 2106.04(b-c). Polynucleotides capable of binding to mRNA includes antisense RNA, miRNA, cfDNA, ctDNA and negative strand genomic DNA.
2. Regarding the probes or detection agents for measuring cell surface CD biomarkers, the claimed scope includes naturally occurring polypeptide and polynucleotide detection reagents such as naturally occurring antibodies to the CD biomarkers.
Step 2A Prong Two: Consideration of Practical Application
The method of claims 33-38 and 44-48 result in determining a probability of breast cancer. The step results in an abstract idea determination and does not recite any additional elements that integrate the abstract idea into a practical application.
The method of claims 50-52 result in a conditional step of determining whether a female subject has or has not developed breast cancer and if so, performing step (c) of administering a breast cancer modulating agents. The Broadest Reasonable Interpretation of this method encompasses determining that the subject does not have breast cancer such that step (c) is not performed. Furthermore, the recited “breast cancer modulating agents” is not a particular treatment and reads on any therapeutic substance to manage or alter cancer growth. These claims therefore also do not recite any additional elements that integrate the abstract idea into a practical application.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than
a drafting effort designed to monopolize the exception.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. measuring a biologic sample obtained from the female subject the expression level of transcriptomic makers of a first panel comprising SOX4, TNFSF10, CD3G, and NR3C2, as in claims 33 and 50.
2. measuring cell surface biomarkers of a second panel comprising CD11b, CD62L, CD86, CD117, CD144, CD177 and CD202b, as in claims 33 and 50.
2. administering a breast cancer modulating agent, as in claim 50.
3. measuring cell surface biomarkers of a second panel comprising as least one of FceRI, HLA-DR, CD69, CD101, CD163, CD170, and CD274, as in claim 34.
4. measuring cell surface biomarkers of a second panel comprising at least one protein biomarker selected from CD3, CD14, CD16, CD15, CD19, CD20,CD56, and CD66b, as in claim 35.
5. measuring a transcript biomarker selected from at least one of FCER 1A, GZMH, KLF 12, HLA- DOA, CX3CR1, HMGB2, LY9, S and KLRB1.
6. measuring a transcript biomarker selected from at least one of TGFBR3, CCL20,CCR3, FN1, ACKR3, IL10,CXCL10,C3, MKI67, HBEGF, C9orf47, CD40, EREG, CXCL9, and SERPINE1.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because measuring gene expression of transcriptomic markers and cell surface biomarkers of known genes is well understood, routine and conventional. The biomarkers recited are well known, routine and conventional for breast cancer analysis. Rossi et al. (US 2012/0046346) teach all of CXCL10, TBP, HMGB2, KLF12, NR3C2, SOX4, CD101, CD11b, CD117, CD14, CD15, KLRB1, CD163, CD16, CD170, CD177, CD19, CCr3, CD20, CD202B, CD3, TNFSF10, CD274, CD3G, CD40, CD62L, CD56, CD66b, CD69, CD86, CD163, HLA-DR, and GAPDH which are the biomarkers recited in claims 33-37, 39-43, and 49-50. These biomarkers are well known as related to cancer including breast cancer, or immune response. Administering a breast cancer a modulating agent after analysis of known genes and markers for breast cancer is also well known, routine and conventional.
Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112-2nd 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 33-52 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 pre-AIA the applicant regards as the invention.
Claims 33, 39,49 and 50 recites measuring expression level of transcriptomic (mRNA) markers. It is unclear what the metes and bound of “(mRNA)” is intended to be. It is unclear if the transcriptomic markers are limited to be limited to mRNA or not. An example such as “(mRNA)” in the claims raises issues of unclarity because the claims do not set forth conditions for when the transcriptomic markers are to be mRNA and when then should be another type of marker. Applicants are advised to delete “(mRNA)” or clarify the metes and bounds of “(mRNA)” by clearly reciting mRNA.
Claim 49 recites ACTBIPO8 which is unclear because gene or protein ACTBIPO8 does not exist. It is unclear if this is a typographical error and the claim should otherwise recite the two house keeping genes ACTB and IPO8. Clarification is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 33-35, 37-41, and 43-52 are rejected under 35 U.S.C. 103(a) as being unpatentable over Liew et al. (US 2007/0213939) in view of Song et al. (Tumor Biology vol. 36 (2015) pgs. 4167-4173) in view of Messeha et al. (European journal of pharmacology vol. 885 (2020) 173419) in view of Bertucci et al. (Human Molecular Genetics vol. 9 (2000) pgs. 2981-2991) in view of and Lu et al. (BioMed research international vol. 2021 (2021) pgs. 1-13) in view of Mehta et al. (Frontiers in immunology vol. 12 (2021) pgs. 1-17), Amin et al. (Indian Journal of Pathology and Microbiology vol. 55 (2012) pgs. 456-460) in view of Toth et al. (Anticancer research vol. 28 (2008) pgs. 1107-1112) and in view of Kultz et al. (Oncogene vol. 39 (2020) pgs. 2877-2889)
Liew et al. teach a method of determining cancer by providing a level of related biomarkers (Abstract), applying the data to a formula which is a logistic regression model (par. 0263) of the same expression as the LOG(P/1-P) formula in claim 33, steps (b), (c) and (d).
Liew et al. teach (par. 0269) that the probabilities calculated from the logistic regression formula are between 0 and 1 (i.e. wherein a score closer to 1.0 represents the likelihood of breast cancer and a probability score value closer to 0.0 represents the likelihood that the female subject has not developed breast cancer), as in claims 33, steps (b),(c) and (c), claim 38, and claim 50, step (b) and 51.
Liew et al. teach that the logistic regression formula is used to test various combination of biomarkers in their Tables 1, 2, 11 and 12 which can be either upregulated or downregulate (par. 0262).
Liew et al. teach (par. 0617) creating classifier gene expression panels for having colorectal cancer and not having colorectal cancer (i.e. comparing the amount measured in step (a) to a reference panel wherein an increased amount or a decreased amount in the first panel and in the second panel indicates that the subject suffers from cancer), as in claim 50.
Liew et al. teach primer sets (i.e. primer pairs) for detecting expression levels of biomarkers in a test subject (par. 0063), as in claim 39.
Liew et al. teach a sensitivity and specificity analysis (par. 0079-0080), as in claim 46.
Liew et al. teach ACTB house keeping gene (par. 0573) and PGK (par 0380 and 0504), as in claim 49.
Liew et al. do not teach their method as specific to breast cancer and taking a biologic sample from a female subject, as in claims 33, 39, 44-45, 47-48, 50 and 52.
Liew et al. do not specifically teach the biomarkers of independent claims 33, 39 and 50 and dependent claims 34-37 and 40-43.
Liew et al. do not teach administering a breast cancer modulating agent, as in claim 50, step (c).
Song et al. (2015) teach (Abstract) that SOX4 overexpression is a biomarker of breast cancer and measure SOX4 mRNA expression, as in claims 33, 39 and 50.
Messeha et al. teach mRNA expression of TNFSF10 (page 5-6, connecting par. and Table 1) as a marker in breast cancer cells, as in claims 33, 39, and 50.
Bertucci teach (abstract; page 2985, col. 1, par.1 and Table 3) mRNA analysis of CD3D as a differentially expressed biomarker for breast cancer patients, as in claims 33, 39 and 50.
Lu et al. teach (title and abstract) NR3C2 related transcriptome profile for invasive beast cancer, as in claims 33, 39 and 50.
Mehta et al. teach (page 3, col 2) CD11b, CD62L, and CD86 expression related to breast cancer and administering tamoxifen (page 8, col.2, par. 2)(i.e. a breast cancer modulating agent), as in claims 33, step (a), claim 39 and claim 50, steps (a) and (c).
Amin et al. teach cytoplasmic derived CD117 expression (Abstract and page 457) in relation to breast cancer analysis, as in claims 33, 39 and 50.
Toth et al. teach (page 1109, col. 1, par. 3) high expression of CD144 in breast cancer, as in claims 33, 39 and 50.
Kultz et al. teach (Abstract) that CD177 expression is a biomarker for breast cancer prognosis, as in claims 33, 39 and 50.
The combination of Liew et al. who teaches primer pairs for biomarker detection in view of the first and second biomarker panels taught by the combination of Song et al., Messeha et al., Bertucci et al., and Lu et al., Mehta et al., Amin et al., Toth et al., and Kultz et al. make obvious probes for measuring mRNA expression of the listed genes and detection reagents for expression levels of cell surface biomarkers, as in the kit of claim 39.
Mehta et al. teach HLA-DR and CD14 (page 3, col. 2, line 2-3 from bottom) as expressed by breast cancer patients, as in claims 34-35 and 40-41.
Mehta et al. teach CCL20 (Figure 2) as related to the breast cancer pathway, CXCL10 and CXCL9 (page 7, col. 1, par. 1; col. 2; and Figure 2) and CD40 (page 9, col. 2, par. 2) are related to breast cancer, as in claims 37 and 43.
Lu et al. teach their biomarker for determining new primary tumor or recurrence (page 2, col. 2, par. 2) and early detection and screening (page 1, col. 2, par. 1), as in claim 47-48.
Lu et al. teach breast carcinoma and tumor serum biomarkers (page 8, col. 2), as in claims 44-45.
Lu et al. teach (page 10, col. 1, par. 2) samples from subjects with tumors (i.e. previously diagnosed with breast cancer), as in claim 52.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teaching of Liew et al. for calculating a probability of cancer with linear regression analysis of biomarker amounts with biomarkers that are known to indicate breast cancer and breast cancer prognosis as taught by the combination of Song et al., Messeha et al., Bertucci et al., and Lu et al., Mehta et al., Amin et al., Toth et al., and Kultz et al. It would be obvious to one of skill in the art to combine the teachings of individual biomarkers known for breast cancer detection as taught in Song et al., Messeha et al., Bertucci et al., and Lu et al., Mehta et al., Amin et al., Toth et al., and Kultz et al. to thereby form panels. It would be further obvious to use the panels’ biomarker levels as variables in the regression calculation of Liew et al. Liew et al. teach that the regression can be used for various panels (par. 0262) and one of ordinary skill would recognize that the logistic regression is not limited to biomarkers of a specific cancer type. Therefore the combination of known elements taught by Liew et al., Song et al., Messeha et al., Bertucci et al., and Lu et al., Mehta et al., Amin et al., Toth et al., and Kultz et al. would produce a predictable result of using logistic regression to fit expression amounts of known breast cancer biomarkers to determine a probability of breast cancer.
Claims 36 and 42 are rejected under 35 U.S.C. 103(a) as being unpatentable over Liew et al. in view of Song et al. in view of Messeha et al. (in view of Bertucci et al. in view of and Lu et al. in view of Mehta et al., Amin et al. in view of Toth et al. and in view of Kultz et al. as applied to claims 33-35, 37-41, and 43-52 above and further in view of Tardaguila et al. (Cancer research vol. 73 (2013) pgs. 4461-4473).
Liew et al. in view of Song et al. in view of Messeha et al. (in view of Bertucci et al. in view of and Lu et al. in view of Mehta et al., Amin et al. in view of Toth et al. and in view of Kultz et al. make obvious analyzing a panels of breast cancer biomarkers to determine probability of breast cancer, as recited in claims 33-35, 37-41, and 43-52 above.
Liew et al. in view of Song et al. in view of Messeha et al. (in view of Bertucci et al. in view of and Lu et al. in view of Mehta et al., Amin et al. in view of Toth et al. and in view of Kultz et al. do not teach including CX3CR1 mRNA expression in the breast cancer probability calculation, as recited in claims 36 and 42.
Tardaguila et al. teach (page 4464, col. 2) CX3CR1 mRNA expression related to breast cancer, as in claims 36 and 42.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the breast cancer panel regression analysis as made obvious by Liew et al., Song et al., Messeha et al., Bertucci et al., and Lu et al., Mehta et al., Amin et al., Toth et al., and Kultz et al. with additional breast cancer biomarker CX3CR1 as taught by Tardaguila et al.
It would be obvious to one of skill in the art to combine the teachings of individual biomarkers known for breast cancer detection as taught in Song et al., Messeha et al., Bertucci et al., and Lu et al., Mehta et al., Amin et al., Toth et al., and Kultz et al. with the teachings of Tardaguila et al. for CX3CR1 mRNA expression analysis for breast cancer. Tardaguila et al. teach that CX3CR1 is downmodulated in beast carcinomas (page 4461, col. 2, par. 1) and reported in different types of cancer cell lines including those from breast (page 4461, col. 2, par. 2). Therefore the combination of known elements taught by Liew et al., Song et al., Messeha et al., Bertucci et al., and Lu et al., Mehta et al., Amin et al., Toth et al., Kultz et al. and further in view of Tardaguila et al. would produce a predictable result of using logistic regression to fit expression amounts of known breast cancer biomarkers which includes CX3CR1 to determine a probability of breast cancer.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-7035. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Anna Skibinsky/
Primary Examiner, AU 1635
Prosecution Insights