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 .
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.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 58-67), drawn to methods of diagnosing and treating thyroid carcinomas (metastatic differentiating or medullary), in the reply filed on 04/17/2026, is acknowledged. Hence, claims 48-57 are withdrawn from further consideration pursuant to 37 CFR 1,142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Status of the Claims
Applicant has amended claims 58 and 62. Claims 58-67 are pending and examined herein.
Priority
This application, 18/272,591, filed 07/16/2023, is a 371 of PCT/IL2022/050067 filed on 01/17/2022, and claims benefit of provisional application 63/138,481 filed on 01/17/2021. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 01/17/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 07/16/2023 are acknowledged and have 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 58, 60, 62, and 65 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 58 and 62 are indefinite because they recite “…loading said sample from step (a) to the device of claim 48…”. This claim language renders claims 58 and 62 dependent on claim 48, which is not included in the elected claim group, and is therefore not technically being examined. It is suggested that the Applicant incorporate all of the limitations of claim 48 into the elected claims.
Additionally, claims 58 and 62 recite “said signal” which lacks antecedent support, as a signal was not previously recited in a claim that is included in the elected claim group.
Claims 58 and 62 also recite “a biomarker” with regards to thyroid carcinomas. This recitation renders the claims indefinite because it is unclear what biomarkers are being measured that are capable of indicating the presence of a cancerous thyroidal cell.
Claims 60 and 65 recite “…further comprising determining a progression stage of…”. The claims are indefinite because there are multiple possible conflicting interpretations based on the claim language provided. For example, it is unclear if the claim language is to be interpreted as the biomarker is being used to determine the progression stage of the thyroid carcinoma. Or alternatively, whether the claim language is to be interpreted as the progression stage of the thyroid carcinoma is being determined in addition to/in parallel with the biomarker. As there are multiple potential conflicting interpretations of the claim language, these claims are indefinite.
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 58-60 and 62-65 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception and a law of nature without significantly more. Claim 58 recites “A method for diagnosing metastatic differentiating thyroid carcinoma (DTC) in a subject, comprising the steps of: a. providing a sample comprising an extra thyroidal tissue or a fragment thereof derived from said subject; and b. loading said sample from step (a) to the device of claim 48, and detecting said signal, wherein detection of said signal indicates a presence of a biomarker of DTC in said sample, and wherein the presence of said biomarker of DTC in said sample is indicative of a cancerous thyroidal cell being present in said sample, thereby diagnosing metastatic DTC in said subject”. Similarly, claim 62 recites “A method for diagnosing medullary thyroid carcinoma (MTC) in a subject, comprising the steps of: a. providing a sample comprising a thyroidal tissue or a fragment thereof derived from said subject; and b. loading said sample from step (a) to the device of claim 48, and detecting said signal, wherein detection of said signal indicates a presence of a biomarker of MTC in said sample, and wherein the presence of said biomarker of MTC in said sample is indicative of a cancerous thyroidal parafollicular cell being present in said sample, thereby diagnosing metastatic MTC in said subject”.
The claims are directed to a judicial exception, mainly they are abstract ideas, specifically, mental processes that can be performed in the human mind, and/or are merely observing naturally occurring correlations (laws of nature/natural correlation). These judicial exceptions are not integrated into a practical application because there is no practical application recited in the claims such as performing a treatment in a way that is particular, and not merely instructions to "apply" the exception in a generic way. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps amount to mere data gathering that does not go beyond well-understood, routine, and conventional activity; as detailed below.
Step 1 – Whether a claim is to a statutory category - YES
The invention of claim 58 is directed to a method for diagnosing metastatic differentiating thyroid carcinoma (DTC) in a subject, comprising loading a sample from a subject into a device that detects a signal that indicates the presence of a biomarker, which indicates the presence of a cancerous thyroidal cell and diagnosing the subject with DTC. Similarly, the invention of claim 62 is directed to a method for diagnosing medullary thyroid carcinoma (MTC) in a subject, comprising loading a sample from a subject into a device that detects a signal that indicates the presence of a biomarker, which indicates the presence of a cancerous thyroidal cell and diagnosing the subject with MTC. Therefore, the instantly claimed invention falls into one of the four statutory categories.
Step 2A Prong 1 – Whether the claim is directed to a judicial exception (i.e. Does the claim recite an abstract idea, law of nature, or natural phenomenon?) - YES
Claims 58 and 62 recite the following steps which fall under mental processes and/or natural correlation:
Claims 58 and 62 disclose methods for diagnosing thyroid carcinomas by loading a sample into a device to detect a biomarker which indicates the presence of a cancerous thyroidal cell in the subject and therefore, diagnosing the subject with a thyroid carcinoma (DTC or MTC). The broadest reasonable interpretation of this step is diagnosing a subject with a one of the indicated thyroid carcinomas if any amount of the biomarker is detected in the subject’s sample. This limitation recites a law of nature which is a judicial exception, because it is merely observing the correlation between a naturally occurring biomarker and its relationship to a disease/disease state (DTC/MTC).
Regarding the identification of a correlation between the presence of a biomarker in a bodily sample and disease state the courts have held similar claims to be laws of nature and/or natural phenomena, as in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017) which involved claims to simply instruct a user to apply a natural law, by correlating naturally occurring enzyme levels with disease risk. In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services V. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring levels of a biomarker that indicates the presence of a cancerous thyroidal cell in a subject’s tissue sample, indicating DTC or MTC.
The correlation between the recited biomarkers of DTC/MTC and disease is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility.
The step of “diagnosing” also constitutes an abstract mental process, involving assessing the presence of the biomarker in a test sample, and then making an evaluation or judgment as to whether the test subject has a particular disease. The “diagnosing” step could be performed in the human mind, or by a human using pen and paper, insofar as it reads on comparing levels and drawing conclusions from this about the health status of a subject.
Thus, claims 58 and 62 fall into a judicial exception.
Step 2A: Prong 2 - Does the claim recite additional elements that integrate the judicial exception into a practical application? The Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception.
Claims 58 and 62 do not recite any additional element that integrate the exception into a practical application of the exception. The claims also recite the additional steps of providing a sample comprising a tissue or a fragment thereof derived from said subject; and loading said sample into a device capable of detecting said signal, which are insufficient to integrate the exception into a practical application because the purpose is merely to obtain data to observe a naturally occurring correlation.
Regarding dependent claims 59, 60, and 63-65, they do not recite any additional elements that integrate the judicial exception into a practical application. The additional steps of selecting the tissue from which the sample is chosen (claims 59 and 63), detecting the signal by qualitatively determining, quantitatively determining, or both (claims 59 and 64), and determining a progression stage of the thyroid carcinoma (claims 60 and 65) are insufficient to integrate the exception into a practical application because the purpose is merely to obtain data to observe a naturally occurring correlation.
Such steps are considered to be insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. V. Sequenom, Inc. (Fed. Cir. 2015) because their purpose is merely to obtain data to use the correlation. Further the step of "detecting said signal" is recited at a high level of generality and is not tied, for example, to any particular device, as discussed in relation to the treatment of the recitation of the device of claim 48 above.
In particular, of the claims indicated in the rejection heading, none of the additionally recited limitations amount to an additional element or combination of elements that apply, rely on, or use the judicial exceptions in a manner that impose meaningful limit on the judicial exceptions.
Step 2B; Whether the additional elements contribute an “inventive concept”. In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05.
Briefly, the claims 58 and 62 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because of the following reasons. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, has been found to be insufficient to add “significantly more” (MPEP 2106.05(I)(A)).
The additional steps of providing a sample comprising a tissue or a fragment thereof derived from said subject and loading said sample into a device capable of detecting said signal (claims 58 and 62), selecting the tissue from which the sample is chosen (claims 59 and 63), detecting the signal by qualitatively determining, quantitatively determining, or both (claims 59 and 64), and determining a progression stage of the thyroid carcinoma (claims 60 and 65), do not add a meaningful limitation to the instant method as they would have been routinely used by those of ordinary skill in the art as supported by Cunha et al. (2007). “Thyroglobulin detection in fine-needle aspirates of cervical lymph nodes: a technique for the diagnosis of metastatic differentiated thyroid cancer”. European Journal of Endocrinology, 157(1), 101-107, (herein referred to as Cunha), Lyu et al. (CN 111175521 A), (herein referred to as Lyu), Marks et al. (WO 2020141525 A1), (herein referred to as Marks), McLeod et al. (2014). “Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis”. Thyroid, 24(1), 35-42, (herein referred to as McLeod), and Yip et al. (2011). “Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma”. Surgery, 150(6), 1168-1177.
Cunha teaches the measurement of thyroglobulin (Tg) in fine-needle aspirates of cervical lymph nodes for the diagnosis of metastatic differentiated thyroid cancer (abstract). Furthermore, Cunha teaches that thyroglobulin was quantitatively measured in the aspiration washout using immunometric chemiluminescent assay, and measurement of anti-Tg antibodies (FNA-TgAb) was carried out in half of all patients’ aspirates using a solid-phase, enzyme labelled, chemiluminescent sequential immunometric assay (page 102, column 2, 1st full paragraph). Cunha also teaches that their results indicate that lymph nodes aspirates Tg is specific for the detection of loco-regional metastases of DTC, even in cystic metastases of PTC (page 105, column 1, 9th paragraph to column 2, 1st paragraph).
Lyu teaches a device and method for rapid diagnosis of medullary thyroid carcinoma (MTC) and lymph node metastasis in a subject (abstract, Figs. 1 and 2). Lyu also teaches that the device detects calcitonin as a biomarker of a medullary thyroid carcinoma and lymph node metastasis using lateral flow-based immunofluorescence detection ([0042], [0050-0062]).
Marks teaches a rapid diagnostic device through detection of an analyte ([027-028]). Specifically, Marks teaches that the device comprises of 4 sections that are sequentially and linearly coupled to each other ([006]). Marks teaches these sections are in liquid communication allowing sequential lateral flow of liquid through the sections ([006]).
McLeod teaches the prognosis of differentiated thyroid cancer in relation to serum thyrotropin (TSH) and thyroglobulin antibody status at time of diagnosis (abstract). Additionally, McLeod teaches the classification of disease stage and its association with serum TSH and perioperative antithyroglobulin antibodies (TgAb).
Yip teaches the method of measuring preoperative basal calcitonin and tumor stage and their correlation with postoperative calcitonin normalization in patients undergoing initial surgical management of metastatic medullary thyroid carcinoma (abstract). More specifically, the patient’s serum calcitonin and carcinoembryonic antigen (CEA) levels were measured via immunoassay prior to surgery (page 1169, column 2, 2nd paragraph). Additionally, Yip teaches that patients were staged to determine the extent of disease (MTC) according to the AJCC Cancer Staging Manual, 7th edition (page 1171, column 1, 1st full paragraph; Table III).
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to a law of nature and abstract idea without significantly more. For additional guidance, applicant is directed generally to MPEP § 2106.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 62-64 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lyu et al. (CN 111175521 A).
It is noted that claim 48 is non-elected and thus the limitations of the device of claim 48 are not read into claims 62-64; however, in the interest of compact prosecution, claims 62-64 are examined using any device capable of detecting MTC.
Regarding claim 62, Lyu teaches a device and method for rapid diagnosis of medullary thyroid carcinoma (MTC) and lymph node metastasis in a subject (abstract, Figs. 1 and 2). Lyu also teaches that the device detects calcitonin as a biomarker of a medullary thyroid carcinoma and lymph node metastasis using lateral flow-based immunofluorescence detection ([0042], [0050-0062]). Furthermore, Lyu teaches that calcitonin was measured in a sample collected by puncturing the suspected medullary thyroid cancer (thyroid glands and lymph nodes) with a fine needle and collecting the sample in a connected syringe ([0040]; [0053]). Additionally, Lyu teaches that the sample is placed in the sample area of the CT fluorescence immunochromatographic test paper, which is then incubated before being placed in a portable fluorescence immunoassay analyzer which gives the output of a quality control band C value and detection band in the fluorescence immunochromatography test paper T value ([0055-0056]). When the ratio of T/C > 0.5, the result is positive, indicating that the concentration of CT in the tissue fluid of the puncture is high, which can be identified as MTC or lymph node metastasis; When T/C<0.5, the result is negative, indicating that the CT concentration in the tissue fluid of the puncture is low, and it can be identified as non-MTC or no lymph node metastasis ([0058-0059]).
Regarding claim 63, Lyu teaches that the MTC comprises metastatic MTC ([002]).
Regarding claim 64, Lyu teaches that said detecting comprises quantitatively determining a signal via fluorescence immunochromatography ([0056]).
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.
Claims 58 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Cunha et al. (2007). “Thyroglobulin detection in fine-needle aspirates of cervical lymph nodes: a technique for the diagnosis of metastatic differentiated thyroid cancer”. European Journal of Endocrinology, 157(1), 101-107, (herein referred to as Cunha), in view of Lyu et al. (CN 111175521 A), (herein referred to as Lyu), and Marks et al. (WO 2020141525 A1), (herein referred to as Marks).
It is noted that claim 48 is non-elected and thus the limitations of the device of claim 48 is not read into claims 58-59; however, in the interest of compact prosecution, claims 58-59 are examined using any device capable of detecting DTC.
Regarding claims 58 and 59, Cunha teaches the measurement of thyroglobulin (Tg) in fine-needle aspirates of cervical lymph nodes for the diagnosis of metastatic differentiated thyroid cancer (abstract). More specifically, Cunha teaches performing lymph nodes aspirates on 67 patients with enlarged neck lymph nodes, which were divided into two groups (page 102, column 1, 3rd paragraph). One group consisted of 16 patients that presented with recently diagnosed lymphadenopathy or suspicious thyroid nodules with neck lymph node enlargement (page 102, column 1, 4th paragraph). The second group of 51 patients had previous diagnosis of DTC (48 papillary and 3 follicular) and had been treated with either total or near total thyroidectomy, followed by 131I ablation therapy (page 102, column 1, 5th paragraph). Furthermore, Cunha teaches that thyroglobulin was quantitatively measured in the aspiration washout using immunometric chemiluminescent assay, and measurement of anti-Tg antibodies (FNA-TgAb) was carried out in half of all patients’ aspirates using a solid-phase, enzyme labelled, chemiluminescent sequential immunometric assay (page 102, column 2, 1st full paragraph). Finally, Cunha teaches that their results indicate that FNAB-Tg is specific for the detection of loco-regional metastases of DTC, even in cystic metastases of PTC (page 105, column 1, 9th paragraph to column 2, 1st paragraph).
However, Cunha does not teach using device capable of detecting DTC.
Lyu teaches a device and method for rapid diagnosis of medullary thyroid carcinoma (MTC) and lymph node metastasis in a subject (abstract, Figs. 1 and 2). Lyu also teaches that the device detects calcitonin as a biomarker of a medullary thyroid carcinoma and lymph node metastasis using lateral flow-based immunofluorescence detection ([0042], [0050-0062]). Furthermore, Lyu teaches that calcitonin was measured in a sample collected by puncturing the suspected medullary thyroid cancer (thyroid glands and lymph nodes) with a fine needle and collecting the sample in a connected syringe ([0040]; [0053]). Additionally, Lyu teaches that the sample is placed in the sample area of the CT fluorescence immunochromatographic test paper, which is then incubated before being placed in a portable fluorescence immunoassay analyzer which gives the output of a quality control band C value and detection band in the fluorescence immunochromatography test paper T value ([0055-0056]). When the ratio of T/C > 0.5, the result is positive, indicating that the concentration of CT in the tissue fluid of the puncture is high, which can be identified as MTC or lymph node metastasis; When T/C<0.5, the result is negative, indicating that the CT concentration in the tissue fluid of the puncture is low, and it can be identified as non-MTC or no lymph node metastasis ([0058-0059]).
Marks teaches a rapid diagnostic device through detection of an analyte ([027-028]). Specifically, Marks teaches that the device comprises of 4 sections that are sequentially and linearly coupled to each other ([006]). Marks teaches these sections are in liquid communication allowing sequential lateral flow of liquid through the sections ([006]). Marks also teaches that section 1 comprises a sample collecting surface ([007]), and section 2 comprising a probing molecule (“recognition molecule having specific affinity to the analyte…” – [007]), wherein the probing molecule is linked to a reporter molecule, and wherein the reporter molecule generates a signal/trigger ([007]). Marks also teaches that section 3 comprises a surface functionalized with an analyte or equivalent thereof ([0119]), and section 4 comprises a surface in contact with a substrate molecule generating a signal in response to the trigger ([007]).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for diagnosing metastatic differentiating thyroid carcinoma taught by Cunha, to utilize a lateral flow-based immunofluorescence detection device for rapid diagnosis of thyroid carcinoma, as taught by Lyu, with the 4-section structure discussed above, as taught by Marks. The modification would be obvious as it is merely applying a known technique (rapid measurement of a biomarker for diagnosis of thyroid carcinoma) and a known device (lateral-flow technology to measure analytes) ready for improvement to yield the predictable result of rapid diagnosis of metastatic differentiating thyroid carcinoma.
A skilled artisan would have been motivated to make these modifications to the method taught by Cunha because such lateral-flow devices to measure analytes are compact, fast, and easy to use. A person of ordinary skill would have had a reasonable expectation of success in making these modifications because the art demonstrates that: thyroglobulin can act as a diagnostic biomarker for metastatic differentiating thyroid carcinoma, lateral-flow devices can be used to measure thyroid carcinoma biomarkers, and the use of such devices are well-understood, routine, and conventional activity in the field of medical diagnostics.
Claims 60 and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Cunha in view of Lyu and Marks as applied to claims 58 and 59 above, and further in view of McLeod et al. (2014). “Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis”. Thyroid, 24(1), 35-42, (herein referred to as McLeod).
The teachings of Cunha in view of Lyu and Marks are incorporated herein.
Regarding claim 60, Cunha in view of Lyu and Marks recites all of the limitations of claim 58 of the application but does not recite determining a progression stage of the metastatic differentiated thyroid cancer (DTC) in the subject.
However, McLeod teaches the prognosis of differentiated thyroid cancer in relation to serum thyrotropin (TSH) and thyroglobulin antibody status at time of diagnosis (abstract). Additionally, McLeod teaches the classification of disease stage and its association with serum TSH and perioperative antithyroglobulin antibodies (TgAb). Furthermore, McLeod teaches that there are multiple disease classification methods (page 36, column 2, 2nd full paragraph). The results from Mcleod teach that preoperative serum TSH level is associated with higher DTC stage, gross extrathyroidal extension, and neck node metastases (abstract – Conclusions).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Cunha in view of Lyu and Marks to determine a progression stage of the metastatic DTC in the subject, as taught by McLeod, as it represents merely the application of a known technique (staging of differentiated thyroid cancer) to a known method (diagnosing metastatic differentiating thyroid carcinoma) , that when combined merely performs the same function as it does separately.
A skilled artisan would have been motivated to make these modifications to the method taught by Cunha in view of Lyu and Marks because disease staging allows for a more objective measurement and monitoring of a patient’s disease state and condition, which allows for more informed decisions to made regarding treatment of the disease to ensure better outcomes. A person of ordinary skill would have had a reasonable expectation of success in making these modifications because the art demonstrates that disease staging with regards to the prognosis of thyroid carcinoma is practice that is well-understood, routine and conventional in the field, with several methods of classification available.
Regarding claim 61, Cunha teaches treating the subject diagnosed with metastatic DTC with an effective amount of anti-metastatic DTC therapy, specifically by total thyroidectomy with lymph node dissection performed in 14 patients and 16 previously biopsied lymph nodes were identified and excised for histological examination (page 103, column 2, 1st full paragraph). Cunha also teaches that patients underwent thyroidectomy with modified radical neck dissection followed by radioactive iodine therapy (page 103, column 2, 3rd paragraph to page 104, column 1, 1st paragraph).
Claims 65-67 are rejected under 35 U.S.C. 103 as being unpatentable over Lyu as applied to claims 62-64 above, in view of Yip et al. (2011). “Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma”. Surgery, 150(6), 1168-1177, (herein referred to as Yip).
It is noted that claim 48 is non-elected and thus the limitations of the device of claim 48 is not read into claims 65-67; however, in the interest of compact prosecution, claims 65-67 are examined using any device capable of detecting MTC.
The teachings of Lyu are incorporated herein.
Regarding claim 65, Lyu recites all of the limitations of claim 62 of the instant application but does not teach determining a progression stage of MTC in the subject, or treating the subject diagnosed with MTC with an effective amount of anti MTC therapy.
Yip teaches the method of measuring preoperative basal calcitonin and tumor stage and their correlation with postoperative calcitonin normalization in patients undergoing initial surgical management of metastatic medullary thyroid carcinoma (abstract). More specifically, the patient’s serum calcitonin and carcinoembryonic antigen (CEA) levels were measured via immunoassay prior to surgery (page 1169, column 2, 2nd paragraph). Additionally, Yip teaches that patients were staged to determine the extent of disease (MTC) according to the AJCC Cancer Staging Manual, 7th edition (page 1171, column 1, 1st full paragraph; Table III). Yip teaches that patients underwent treatment for MTC which consisted of complete lymph node dissection in most patients, while some had had ipsilateral modified radical neck dissection (page 1170, column 2, 1st full paragraph). Additionally, Yip teaches that all patients underwent total thyroidectomy as treatment (page 1170, column 2, 1st paragraph).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Lyu to determine a progression stage of the MTC in the subject, as taught by Yip, as it represents merely the application of a known technique (staging of MTC disease state) to a known method (diagnosing MTC), that when combined merely performs the same function as it does separately.
A skilled artisan would have been motivated to make these modifications to the method taught Lyu because disease staging allows for a more objective measurement and monitoring of a patient’s disease state and condition, which allows for more informed decisions to made regarding treatment of the disease to ensure better outcomes. A person of ordinary skill would have had a reasonable expectation of success in making these modifications because the art demonstrates that disease staging with regards to the prognosis of thyroid carcinoma is practice that is well-understood, routine and conventional in the field, and as taught by Yip, there are standardized and readily available protocols for staging MTC progression.
Regarding claims 66 and 67, Yip teaches treating the subjects with MTC by surgical removal of the thyroid and lymph nodes (page 1170, column 2, 1st paragraph; page 1170, column 2, 1st full paragraph).
Conclusion
For all the reasons discussed above, claims 58-67 are rejected and therefore no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER JOSEPH HOFFMAN whose telephone number is (571)272-9080. The examiner can normally be reached 10:00-6:30 M-F.
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/ALEXANDER J. HOFFMAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/ Supervisory Patent Examiner, Art Unit 1677 July 2, 2026
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