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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 8/11/2023 wherein claims 1, 20, 26, 27, 29, 30, 33-36, 38, and 40 were amended; claims 3, 4, 8, 9, 11, 13, 15, 18, 19, 21-25, 28, 31, 32, 37, 39, and 41 were canceled; and claims 42-44 were added.
Note(s): Claims 1, 2, 5-7, 10, 12, 14, 16, 17, 20, 26, 27, 29, 30, 33-36, 38, 40, and 42-44 are pending.
Priority and Priority Document
This application is a 371 of PCT/US21/32080 filed 5/12/2021;
PCT/US21/32080 claims benefit to PRO 63/169,532 filed 4/1/2021 and
SWEDEN SE2050559-0 filed 5/13/2020.
Note(s): The earliest effective filing date is 5/13/2020 as the pending invention is fully supported by SE2050559-0.
Claim Interpretation
Independent claim 1 is directed to a method of treating breast cancer comprising:
a) obtaining a tissue sample of a tumor from a breast cancer patient,
b) determining the expression levels of PD-1 mRNA in the sample,
c) determining that the expression level is below a threshold level,
d) providing intensified treatment as intensified radiotherapy treatment, intensified systemic therapy or mastectomy to the patient.
Independent claim 10 is directed to a PD-1 mRNA-binding nucleotide for use in the diagnosis of breast cancer, where the nucleotide is used for quantifying the level of PD-1 that is expressed in a breast cancer sample, and where low expression of PD-1 indicates that the patients belong to a patient subgroup where intensified radiotherapy treatment is needed.
Independent claim 12 is directed to a method of treating a subject, the method comprising:
identifying an incremental risk to a subject with invasive breast cancer or in situ breast cancer of a local or regional recurrence of an invasive breast cancer based on a level of PD-1 in a sample of an invasive breast cancer in the subject; and
administering an intensified breast cancer therapy to the subject based upon the incremental risk, wherein a higher incremental risk will increase: a) a likelihood of an aggressive breast cancer therapy that is at least more than what would be recommended by the NCCN; b) the aggressiveness of the aggressive breast cancer; or c) both a) and b).
Independent claim 14 is directed to a method of treating a subject, the method comprising:
identifying a subject with invasive breast cancer that has a low level of PD-1; and
administering an intensified treatment to the invasive breast cancer.
Independent claim 16 is directed to a method for preventing an invasive breast cancer recurrence in a subject, the method comprising:
providing a cancer tissue sample from a subject who has invasive breast cancer; analyzing the cancer tissue sample for a level of PD-1; and
administering an intensified treatment if the cancer tissue sample has a low PD-1 level.
Independent claim 17 is directed to a method for preventing an invasive breast cancer recurrence in a subject, the method comprising receiving an intensified treatment if a cancer has a low level of PD-1.
Applicant’s Election
Applicant's election with traverse of Group I (pending claims 1, 2, 5-7, and 42-44) filed 7/6/2026 is acknowledged. The traversal is on the grounds that the Planes-Lainer (Cancers, 2019, Vol. 11, pages 1-25) document did not disclose determining a level of PD-1 expression alone and in the tissue sample. This is found non-persuasive because as the steps being referenced by Applicant are inherent steps that naturally occur when one evaluates the presence of breast cancer as it relates to PD-1 in subject. The rejection below further emphasizes that these are common steps in the art. Thus, the invention does not contain a special technical feature that is distinguished over the art.
In addition, Applicant traverses the restriction on the bases that each independent claim is a part of the overall method of treating breast cancer. This is also found non-persuasive as each method is not only distinct multiple processes, but they have different modes of operation and yield different results depending upon the particular focus of the method. According to standard practice for 371 applications (see MPEP 1893.03(d)), the categories of inventions does not include multiple process. Thus, the invention lacks unity.
For the reasons set forth herein, the restriction requirement is still deemed proper and is therefore made FINAL.
Applicant was respectfully requested to elect a species based on the components necessary for the desired elected Group (Applicant elected Group I). Applicant’s desired elected species is as follows: (1) type of breast cancer is early stage invasive breast cancer; (2) the PD-1 agent is antisense oligonucleotide that binds PD-1 mRNA ; (3) radiotherapeutic process was elected; (4) the mRNA binding molecule is polynucleotide probe3 that hybridizes to PD-1 mRNA having the sequence of SEQ ID No. 1 and is at least 18 nucleotides long; (5) the housekeeping gene is GAPDH; (6) the BED dosages is a dose of 67 Gy or more; (7) the risk assessment is not a continuous risk assessment; (8) there were no elected sensitizers to therapy; and (9) the treatment guidelines are those of NCCN.
Independent claim 1 is directed generally to a method of treating breast cancer comprising:
a) obtaining a tissue sample of a tumor from a breast cancer patient,
b) determining the expression levels of PD-1 mRNA in the sample,
c) determining that the expression level is below a threshold level,
d) providing intensified treatment as intensified radiotherapy treatment, intensified systemic therapy or mastectomy to the patient
Based on Group I claims (claims 1, 2, 5-7, and 42-44) and Applicant’s elected species, claims 1, 6, 7, and 42-43 read on the elected species. The search was not extended beyond the elected species because prior art was found to reject the claims.
Withdrawn Claims
Claims 5, 10, 12, 14, 16, 17, 20, 26, 27, 29, 30, 33-36, 38, and 40 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention/species.
Information Disclosure Statement
The information disclosure statement filed 7/6/2026 was considered.
112 Second Paragraph Rejections
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, 2, 6, 7, and 42-44 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 1, 2, 6, and 7: Independent claim 1 is ambiguous because the term “intensified” in lines 6 and 7 is a relative term which renders the claim indefinite. The term “intensified” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, one cannot readily determine the metes and bounds of the term. Furthermore, since claims 2, 6, and 7 depend upon independent claim 1 for clarity, the claims are also vague and indefinite.
Claim 1: The claim recites the limitation "the step" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 2: Did Applicant intend to insert ‘and’ after ‘treatment’ in line 6?
Note(s): Claim 2 also contains the term ‘intensified’ like independent claim 1.
Claim 42: The claim is ambiguous because periodically guidelines are updated. As a result, it is unclear what the metes and bounds of the claims are as they will vary as the guidelines are modified. In addition, the claim makes reference to any therapy that is above the guidelines. Is the therapy Applicant is referencing, radiotherapy, a mastectomy, systemic therapy or some other treatment?
Claim 42: Should the term ‘and’ be inserted before ‘ignoring the PD-1 marker state’? It is unclear how the phrase applies to claim 42.
Claim 43: The claim is ambiguous because it is unclear shat standard recommended treatment Applicant is referencing. As techniques for evaluating breast cancer a what becomes ‘standard recommendations’ will evolve as well. Thus, one cannot determine the metes and bounds of the claim. Likewise, the boosting dose will also change.
Claim 43: Applicant intend to add ‘and’ after the last occurrence of ‘the’ in line 5 to close the Markush grouping?
Claim 43: The claim recites the limitations “the subject” (lines 3 and 4), “the fraction: (line 5)”, and "the number of fractions" (lines 5-6). There is insufficient antecedent basis for this limitation in the claim.
Claim 44: The claim is ambiguous because one cannot determine the mete and bounds of the claim because the claim is dependent upon current boosting guidelines that will evolve with research and time. Thus, one cannot ascertain the scope of the claim.
103 Rejection
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 2, 6, 7, and 42-44 are rejected under 35 U.S.C. 103 as being unpatentable over Yeong et al (Journal for ImmunoTherapy of Cancer, 2019, Vol. 7, No. 34, pages 1-13) in view of Smit et al (US 2004/0245483) with National Center for Biotechnology Information (NCBI) which (NCBI Reference Sequence NM005018.3) cited as an evidentiary reference.
Independent claim 1 is directed to a method of treating breast cancer comprising:
a) obtaining a tissue sample of a tumor from a breast cancer patient,
b) determining the expression levels of PD-1 mRNA in the sample,
c) determining that the expression level is below a threshold level,
d) providing intensified treatment as intensified radiotherapy treatment, intensified systemic therapy or mastectomy to the patient.
Claim 2 is directed to the method of claim 1 where the intensified treatment comprises intensified radiotherapy treatment.
Claim 6 is directed to the method of claim 1 where the breast cancer is an early-stage invasive breast cancer or breast cancer in situ.
Claim 7 is directed to the method of claim 1 where the expression level of PD-1 is determined by detecting the amount of PD-1 mRNA in the sample.
Yeong et al is directed to understanding the role of programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) in triple negative breast cancer (TNBC) (see entire document, especially, abstract). In the materials and methods section, samples were obtained from TNBC patients prior to the patients undergoing adjuvant chemotherapy or radiotherapy (steps a) and d) in independent claim 1 are met; it also reads on claim 2). Yeong et al disclose that tumors were types, staged, and graded according to the World Health Organization, American Society of Clinical Oncology College of American Pathologists guidelines. Associated ductal carcinoma in situ and lymphovascular invasion were evaluated from the obtained samples (this reads on claim 6) (page 2, right column, first complete paragraph).
Tissue microarray (TMA) sections were labeled with antibodies against PD-1 (pages 2-3, bridging paragraph). The number of PD-1+ immune infiltrates was counted and samples were grouped into ‘high’ and ‘low’ categories according to whether or not the PD-1+ immune infiltrate count was above the median or equal to or below the median (this process encompasses Applicant’s steps b) and c) in claim 1) (page 3, left column, first complete paragraph).
Yeong et al disclose that mRNA levels were evaluated (this reads on claim 7) (page 1, abstract; page 5, left and right columns, bridging paragraph). Also, for the record, it is noted that the PD-1 mRNA of Applicant SEQ ID No. 1, is that of set forth in the data from the National Center for Biotechnology Information (NCBI) which is evidenced by the NCBI Reference Sequence NM005018.3 which is homo sapiens programmed cell death (PDCD1), mRNA.
For the reasons set forth supra, the limitations of claims 1, 2, 6, and 7 are met.
Claim 42 is directed to the method of claim 1 wherein the intensified treatment comprises a therapy above the guidelines in the NCCN, ESMO, Clinical Practice Recommendations Australia, NICE guideline, or ignoring the PD-1 marker state.
Claim 43 is directed to the method of claim 1 wherein the intensified radiotherapy treatment comprises at least one of: a dose of 67 Gy or more, adding a boosting dose to a standard recommended treatment for the subject when the standard recommended treatment does not include a boosting dose, increasing a boosting dose beyond the standard amount for the subject, increasing the fraction dose on a per fraction basis above the standard for the subject, or increasing the number of fractions of a recommended dose above the standard for the subject.
Claim 44 is directed to the method of claim 1 wherein
(a) for a subject with no boost otherwise recommended, the intensified radiotherapy treatment is whole breast external radiotherapy, partial breast radiotherapy or brachytherapy or a combination thereof, with a biologically effective dose of (BED) of 73 Gy or more with a tumor alpha/beta ratio of 5 or a BED of 78 Gy or more with a tumor alpha/beta ratio of 4 or a BED of 87 Gy or more with a tumor alpha/beta ratio of 3 or a BED of 104 Gy or more with a tumor alpha/beta ratio of 2; or
(b) for a subject with a boost otherwise recommended, the intensified radiotherapy treatment is one or more of whole breast external radiotherapy, partial breast radiotherapy or brachytherapy or a combination thereof, with a biologically effective dose of (BED) of 93 Gy or more with a tumor alpha/beta ratio of 5 or a BED of 100 Gy or more with a tumor alpha/beta ratio of 4 or a BED of 111 Gy or more with a tumor alpha/beta ratio of 3 or a BED of 133 Gy or more with a tumor alpha/beta ratio of 2 for patients who are recommended a boost according to the current guidelines.
While Yeong et al fail to disclose the limitations of claims 42-44, Smit et al is made of record for their teachings of a radiation application method and device for applying radiation to a wound cavity result from a lumpectomy (see entire document, especially, abstract). Smit et al disclose that the alpha/beta ratio for cancerous tissue is generally about 7 Gy and for the relevant normal tissues of the breast, it is 2 Gy (page 3, paragraph [0050]. In addition, the document discloses that for a dose of 50 Gy delivered in 5 weeks, the Biologically Effective Damage (BED) to cancer tissue is 64.28 Gy (page 3, paragraph [0051]). For larger amounts of a boost dose, the BED(7) is 77.14 Gy. Single doses in tissue in contact with the surface of the applicator may be calculator such that BED (7) is 84 Gy (page 3, paragraphs [0053] – [0055]; Table 1, and Table 2) (the limitations of claims 43 and 44 are met).
In regard to the limitations of claim 42, Yeong et al disclose radiotherapy and Smit et al disclose radical doses of 50 Gy or more (page 2, paragraph [0034]; page 3, paragraphs [0050] – [0055], Table 1, and Table 2). It would have been obvious to one of ordinary skill in the art prior to Applicant’s effective dated to generate various BED, alpha/beta ratio amounts, and intensified treatment based on the guidelines present in NCCN, ESMO, Clinical Practice Recommendations, NICE because based on MPEP 2144.05, it would have been obvious to optimize the various BED, alpha/beta ratio values, and intensified treatment guidelines since the Smit et al disclose the general conditions as a result it is not inventive to discover the optimum or workable ranges (values) by routine experimentation. Furthermore, since both Yeong et al and Smit are directed to treating breast cancer, the references may be considered to be within the same field of endeavor. Thus, the reference teachings are combinable.
For the reasons set forth supra, the limitations of claims 1, 2, 6, 7, and 42-44 are rendered obvious by the cited prior art.
Comments/Notes
Applicant’s SEQ ID No. 1 is made of record from documentation from National Center for Biotechnology Information (NCBI) of Homo sapiens programmed cell death 1 (PDCD1), mRNA (5 pages).
Conclusion
Claims 1, 2, 6, 7, and 42-44 are rejected and claims 5, 10, 12, 14, 16, 17, 20, 26, 27, 29, 30, 33-36, 38, and 40 are withdrawn.
Future Correspondences
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
September 5, 2026
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