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 .
The claims dated 6/18/2025 are under consideration.
Election/Restrictions
Applicant’s election of Group II, claims 11-16, in the reply filed on 6/18/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/18/2025.
Applicant’s election without traverse of the species: PLEKHS1 promoter; BRAF; and gain of the long arm (q) of chromosome 1, in the reply filed on 6/18/2025 is acknowledged.
Information Disclosure Statement
The listing of references or citations 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 or cited on a submitted IDS, they have not been considered.
Specification
The abstract of the disclosure is objected to because two copies of the abstract have been provided on 5/4/2022. One is formatted as two paragraphs. The other is a single paragraph, but lacks a space between the first two sentences.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The use of terms that are trade names or marks used in commerce, such as TaqMan™, HiSeq™ or Qubit™, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The references to websites appear on p. 12, line 24 and p. 38, line 23, of the specification as originally filed. It is suggested the “http://” prefix simply be removed from the web address.
Claim Objections
Claim 11 is objected to because of the following informalities: the recites “PLEKHS1 promoter gene” and “TERT promoter gene”, rather than “PLEKHS1 gene promoter” and “TERT gene promoter”. Appropriate correction is required.
Claim Interpretation
The “gene” that is obtained in step (a) is interpreted as being indirectly limited by the language of step (b) to one selected from a PLEKHS1 promoter gene, a TERT promoter gene and a TP53 gene.
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 11-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
The claim(s) recite(s) the following elements:
“confirming whether a mutation is present in any one or more genes selected from the group consisting of a PLEKHS1 promoter gene, a TERT promoter gene and a TP53 gene in the gene of Step a)” (claim 11);
“confirming whether a mutation is present in any one or more genes selected from the group consisting of a BRAF gene and a RAS gene when no mutation is found in Step b)” (claim 11);
“when the mutation in Step b) is confirmed, the individual is determined to be likely to exhibit resistance to radioactive iodine therapy and to die” (claim 13);
“when the mutation in Step c) occurs, the individual is determined to exhibit resistance to radioactive iodine therapy, and when the mutation is not found, the individual is determined to show a good prognosis” (claim 14);
“in Step b), the copy number variations of any one or more selected from the group consisting of, among the genes isolated in Step a),
a) gain of the long arm (q) of chromosome 1;
b) loss of the long arm(q) of chromosome 9;
c) loss of the long arm(q) of chromosome 11; and
d) loss of the long arm(q) of chromosome 22 are further confirmed” (claim 15); and
“when the copy number variation is confirmed, a patient with differentiated thyroid cancer is determined to be likely to exhibit resistance to radioactive iodine therapy and to die” (claim 16).
The two steps of “confirming” are abstract ideas as they can broadly be performed in a purely mental manner, for example, by reading and considering data in a report.
The clause stating “when the mutation in Step b) is confirmed…” sets forth a naturally occurring correlation between a mutation in a sample and the status of the patient. It also broadly encompasses an abstract idea that is determining a patient status based on the confirmation of a mutation.
The clause stating “when the mutation in Step c) occurs…” sets forth a naturally occurring correlation between a mutation in a sample and the status of the patient. It also broadly encompasses an abstract idea that is determining a patient status based on the confirmation of a mutation.
The clause stating “in Step b), the copy number variations of any one or more selected from the group consisting of…”. The element is an abstract idea as it can broadly be performed in a purely mental manner, for example, by reading and considering data in a report.
The clause stating “when the copy number variation is confirmed…” sets forth a naturally occurring correlation between a mutation in a sample and the status of the patient. It also broadly encompasses an abstract idea that is determining a patient status based on the confirmation of a mutation.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations add insignificant extra-solution activity to the judicial exceptions.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims encompass the use of techniques that are at the level of those skilled in the art (p. 7, line 29 to p. 8, line 5), and thus, deemed to be routine and conventional in the field.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 11-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The specification, while being enabling for
A method for providing information for diagnosing or predicting a prognosis of thyroid cancer, the method comprising:
a) obtaining a gene from a thyroid tumor, blood, urine or saliva sample isolated from an individual;
b) assaying for whether a mutation is present in a PLEKHS1 gene promoter, where mutation is selected from C593T and G590A; and
c) assaying for whether a V600E mutation in the BRAF gene is present when no mutation is found in Step b),
does not reasonably provide enablement for
A method for providing information for diagnosing or predicting a prognosis of thyroid cancer, the method comprising:
a) obtaining any gene from any sample isolated from an individual;
b) confirming whether any mutation is present in any one or more genes selected from the group consisting of a PLEKHS1 promoter gene, a TERT promoter gene and a TP53 gene in the gene of Step a); and
c) confirming whether any mutation is present in any one or more genes selected from the group consisting of a BRAF gene and a RAS gene when no mutation is found in Step b).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The claim broadly encompasses obtaining a gene from any sample isolated from an individual for the purpose of providing information for diagnosing or predicting a prognosis of thyroid cancer. Mutations in the genome are the basis for a vast number of cancers. The mutations occur in the cell types that ultimately define the type of cancer. For example, mutations in the cells of the lung lead to lung cancer or mutations in the cells of the colon lead to colon cancer. While metastasis leads to cancer in tissues that are not the origin of the cancer, those cancer cells remain of the cell type of the tissue from which the cancer originated. Further, mutations are largely tissue specific and while the same gene may be mutated in different types of cancers, the specific mutation may not be the same. See Stephens (The Mutational Spectra of Cancer Genes in TCGA Data”. May 10, 2017). The instant specification only looked at thyroid cancer samples (Example 1). No other samples were analyzed and there is no indication or evidence of record that mutations in a normal tissue or non-thyroid tissue are of any use in diagnosing or predicting a prognosis of thyroid cancer.
The instant specification observed the C593T and G590A mutations in PLEKHS1, the V600E mutation in the BRAF gene and the Q61R, Q61L, Q61K, Q12R, Q13R, Q12A, Q13A, Q12C, Q13C, Q12D, Q13D, Q12S, Q13S, Q12V and Q13V mutations in the RAS gene. The claims broadly encompass any and all mutations in the elected genes of PLEKHS1 and BRAF for the purpose of providing information for diagnosing or predicting a prognosis of thyroid cancer. There is no indication or evidence of record that all mutations, other than those identified are present in thyroid cancer samples, provide any useful information.
Undue experimentation is required in order to screen and identify any additional samples and mutations that may be useful in the claimed methods. There is no reasonable expectation of success that any additional sample that may be useful or that any additional mutations may be observed that may be useful.
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 11-16 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 11, it is not clear how the recited preamble is intended to breathe life and meaning into the claims. The preamble of the claim recites “A method for providing information for diagnosing or predicting a prognosis of thyroid cancer”. However, the method steps in the claim only require active method steps of “obtaining a gene”, confirming a mutation is present in PLEKHS1 and a conditional step of confirming a mutation is present in the BRAF gene. Thus, it is unclear if applicant intends to cover any method of performing these steps, or if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If it is the later, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal of providing information for diagnosing or predicting a prognosis of thyroid cancer as set forth by the preamble of the claim. Amending the claim to include an active process step directed towards providing information or diagnosing or predicting prognosis of thyroid cancer may overcome this objection.
Claims 12-16 are similarly indefinite because they directly or indirectly depend from claim 11.
Regarding claims 13-16, the claims use the passive voice, e.g., “are further confirmed”, “is determined”, etc., and is contrasted with the active voice used in claim 11, e.g., “obtaining a gene”, “confirming whether a mutation is present”, etc. It is unclear if applicant intends the language of claims 13-16 to be interpreted as requiring active method steps.
Regarding claim 15, the claim recites “the copy number variations of any one or more selected from the group consisting of, among the genes isolated in Step a), a) gain of the long arm (q) of chromosome 1…and d) loss of the long arm (q) of chromosome 22…”. It is unclear if “among the genes isolated in Step a)” is an alternative within the claimed Markush group, in that the genes isolated in step a) are options along with alternatives a) to d).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 13-16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 13, the claim states that as consequence of confirming a mutation in step (b), the individual is determined to be likely to exhibit resistance to radioactive iodine therapy and to die. The claim does not step forth any additional active method steps or further limit any element of claim 11. Thus, the scope of claim 13 is not any different than claim 11.
Regarding claim 14, the claim states that as consequence of a mutation in step (c) occurring, the individual is determined to exhibit resistance to radioactive iodine therapy. The claim also states that as a consequence of not finding a mutation in step (c), the individual is determined to show a good prognosis. The claim does not set forth any additional active method steps or further limit any element of claim 11. Thus, the scope of claim 14 is not any different than claim 11.
Regarding claim 15, the claim states that as a consequence of confirming a mutation in step (b), a copy number variation is further confirmed. The claim does not set forth any additional active method steps or further limit any element of claim 11. Thus, the scope of claim 15 is not any different than claim 11.
Regarding claim 16, the claim states that as a consequence of having the copy number variation being confirmed, a patient with differentiated thyroid cancer is determined to be likely to exhibit resistance to radioactive iodine therapy and to die. The claim does not set forth any additional active method steps or further limit any element of claim 15. Thus, the scope of claim 16 is not any different than claim 15.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 11-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fredriksson (Nature Genetics. 2014. 46(12):1258-1263 and Online Methods; previously cited).
Regarding claim 11, Fredriksson teaches obtaining genes in DNA from thyroid cancer and confirming a mutation is present at 70 or 73 bp into intron 1 of the PLEKHS1 promoter (p. 1262, left column; and Fig. 1).
Fredriksson anticipates embodiments of claim 11 in which steps (a) and (b) are preformed but not step (c) because a mutation was found in step (b).
Regarding claim 12, Fredriksson teaches the sample is a thyroid cancer or “tumor” sample (Fig. 1).
Regarding claim 13, the claim states a determination that is the consequence of detecting a mutation in step (b). The claim does not further require any active method steps nor does it further limit any of the elements of claim 11.
Fredriksson anticipates claim 13 for the same reason it anticipates claim 11.
Regarding claim 14, the claim states a determination that is the consequence of detecting a mutation in step (c). The claim does not further require any active method steps nor does it further limit any of the elements of claim 11. It is further noted that the consequence of detecting a mutation in step (c) is limited to those embodiments in which step (c) is performed.
Fredriksson anticipates claim 14 for the same reason it anticipates claim 11.
Regarding claim 15, the claim states a further confirmation that is the consequence of detecting a mutation in step (b). The claim does not further require any active method steps nor does it further limit any of the elements of claim 11.
Fredriksson anticipates claim 15 for the same reason it anticipates claim 11. Fredriksson teaches all the active method steps of claims 11 and 15.
Regarding claim 16, the claim states a further determination that is the consequence of detecting a mutation in step (b). The claim does not further require any active method steps nor does it further limit any of the elements of claims 11 and 16.
Fredriksson anticipates claim 16 for the same reason it anticipates claims 11 and 15. Fredriksson teaches all the active method steps of claims 11, 15 and 16.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 11-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fredriksson (Nature Genetics. 2014. 46(12):1258-1263 and Online Methods).
Regarding claim 11, Fredriksson teaches obtaining genes in DNA from thyroid cancer and confirming a mutation is present at 70 or 73 bp into intron 1 of the PLEKHS1 promoter (p. 1262, left column; and Fig. 1). Fredriksson teaches that in 2 of 34 samples, a PLEKHS1 mutation is present.
Fredriksson further teaches confirming whether a mutation in the BRAF gene is present in thyroid cancer (Fig. 3).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have further analyzed thyroid cancer samples for BRAF mutations along with independently determining whether or not PLEKSH1 promoter mutations are present. One would have been motivated to analyze for BRAF mutations because it activates factors that bind a mutant TERT promoter (p. 1261). The proposed modification results in confirming whether BRAF mutations are present in 32 samples that did not have PLEKHS1 promoter mutations.
The above analysis renders obvious embodiments of claim 11 in which steps (a), (b) and (c) are performed.
Regarding claim 12, Fredriksson teaches the sample is a thyroid cancer or “tumor” sample (Fig. 1).
Regarding claim 13, the claim states a determination that is the consequence of detecting a mutation in step (b). The claim does not further require any active method steps nor does it further limit any of the elements of claim 11.
Fredriksson renders obvious claim 13 for the same reason it renders obvious claim 11.
Regarding claim 14, the claim states a determination that is the consequence of detecting a mutation in step (c). The claim does not further require any active method steps nor does it further limit any of the elements of claim 11. It is further noted that the consequence of detecting a mutation in step (c) is limited to those embodiments in which step (c) is performed.
Fredriksson renders obvious claim 14 for the same reason it renders obvious claim 11.
Regarding claim 15, the claim states a further confirmation that is the consequence of detecting a mutation in step (b). The claim does not further require any active method steps nor does it further limit any of the elements of claim 11.
Fredriksson renders obvious claim 15 for the same reason it renders obvious claim 11. Fredriksson teaches all the active method steps of claims 11 and 15.
Regarding claim 16, the claim states a further determination that is the consequence of detecting a mutation in step (b). The claim does not further require any active method steps nor does it further limit any of the elements of claims 11 and 16.
Fredriksson renders obvious claim 16 for the same reason it renders obvious claims 11 and 15. Fredriksson teaches all the active method steps of claims 11, 15 and 16.
Conclusion
No claims allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682