DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This application is the national stage of PCT/KR2022/006198, filed 04/29/2022, claiming foreign priority to KR10-2021-0055921, filed 04/29/2021. It is noted that while a certified copy of the foreign priority document is present in the application file, a certified translation has not been filed; the effective filing date (for purposes of compared the claimed invention to the prior art) is 04/29/2022.
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on 20 April 2026 is acknowledged.
Applicant’s election of the species of the gene TAGLN, a measurement unit configured to measure nucleic acid, and gastric cancer, in the reply filed on 20 April 2026 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)).
While it is noted that the Reply of 20 April 2026 identifies claims 27-31 and 33 as reading on the elected species, as prior art was found to apply against the claims as directed to the elected species (including the single gene TAGLN), gene combinations as set forth in new dependent claim 33 are not under consideration herein. Claims 27-31 read on the elected invention and species.
Claims 19-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 20 April 2026.
Claims 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 20 April 2026.
Claims 27-31 are under consideration herein as directed to the elected species noted above.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see substitute specification page 22. 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.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “measurement unit configured to measure an expression level” in claim 27; “calculation unit configured to calculate a smooth muscle cell (SMC) score” in claim 27; and “output unit configured to output prognosis of cancer….based on the SMC score” in claim 28.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Regarding the limitation “agent binds specifically to the at least one gene” in dependent claim 31, which follows recitation of a requirement for an agent “that is at least one selected from the group consisting of primers, probes, and antisense nucleotides”, while this language is broad, in the context of the claims it embraces oligonucleotides that bind with sufficient specificity to allow for the measurement of expression level of the corresponding gene in any manner (encompassing any of a variety of well-known types of measuring that employ such oligonucleotides, ranging from sequencing by hybridization to gene/allele specific PCR amplification, etc.). It is noted that the claims are indefinite with regard to the structure of the “measurement unit” involved, as is discussed below; however, the language of this claim related to the primers/probes/antisense nucleotides themselves is not considered indefinite.
Claim Rejections - 35 USC § 112(b)/second 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 27-31 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 claims 27-31, independent claim 27 recites the claim limitation “measurement unit configured to measure an expression level…”, which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. While the specification exemplifies use of structures that one of ordinary skill would recognize as having the capability of functioning as a type of “measurement unit”, such as the commercial microarrays disclosed in the examples – and could also envision other prior art structures that could potentially be employed in measuring expression levels, such as thermocyclers, substrates for use in hybridization assays, robotic “lab on a chip” devices, etc. – the specification does not provide guidance as to what structures correspond to the recited “measurement unit configured to measure an expression level”, such that the boundaries of the claims are unclear. With further regard to claim 31, which states that the measurement unit “is configured to measure an expression level of at least one gene using an agent that is at least one selected from the group consisting of primers, probes, and antisense nucleotides, wherein the agent binds specification to the at least one gene”, while this language narrows the claims to structures that could be employed in measuring expression level via a technique employing the recited primers, probes, or antisense nucleotides, it does not clarify the types of structures embraced by the claims (as such reagents could be employed in any of a variety of techniques involving a variety of different known types of structures, including those noted above). Accordingly, the boundaries of the claims with respect to the recited “measurement unit” of the claimed system are not clear. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Regarding claims 27-31, independent claim 27 also recites the claim limitation “calculation unit configured to calculate a smooth muscle cell (SMO) score based on the expression level….measured by the measurement unit”, which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. It is noted that the specification discloses preferred types of SMO scores that might be calculated – e.g., an ”average value of expression levels” or “the average of log intensities of” gene/protein expression levels (paragraphs 86 and 93), or an “expression level value normalized to a housekeeping gene” (paragraph 87) – and teaches publicly available statistical packages/tools to aid in such calculations (paragraph 85), further stating that this unit “may generate and classify information on cancer prognosis prediction according to the calculated score” (paragraph 94). However, while a person of skill in the art would presume based on such disclosures that the “calculation unit” may potentially encompass, e.g., processors usable in executing program instructions, the specification does not provide guidance as to what structures correspond to the recited “calculation unit configured to calculate”, such that the boundaries of the claims are unclear. Accordingly, the boundaries of the claims with respect to the recited “calculation unit” of the claimed system are not clear. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Claim 28 recites the claim limitation “output unit configured output prognosis of cancer….based on the SMC score calculated by the calculation unit”, which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. The specification references an “output unit to output the prediction result” (paragraphs 95-96) or “configured to output the prognosis” (paragraph 97), but provides no guidance as to what structures may correspond to the recited “output unit”. A person of skill in the art could envision examples of structures that might (or might not) be considered an “output unit” – e.g., a computer processor that generates data output, a monitor, printer, and/or phone capable of reporting “output”, etc.. – however, given the lack of guidance provided in the disclosure, it is unknown what the language of the claim may embrace (and what the claim does not encompass). Accordingly, the boundaries of the claims with respect to the recited “output unit” of the claimed system are not clear. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
With regard to the limitations above that invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claim 29 is indefinite over the recitation of the limitation “wherein the cancer is a malignant cancer” because it is unclear how this language further limits what is claimed. While it is noted that the claim is further limiting of the intended use of the claimed system (“for predicting prognosis of cancer”), as all cancers may generally be considered “malignant”, it is not clear how the requirement for “malignant cancer” limits what is claimed. The specification does discuss some types of cancer/characteristics of cancer associated with poorer prognosis than others, but does not definite what features/characteristics correspond to the term “malignant cancer”. Thus, the boundaries of the claim are not clear.
Claim Rejections - 35 USC § 112(a)/first paragraph – Written Description
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 27-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
With regard to satisfying the written description requirement, as discussed in MPEP 2163.02:
Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it")
In this instant case, the limitations at issue in Applicant’s claims are the requirements for a “diagnostic system” including a “measurement unit configured to measure an expression level” (independent claim 27 at a)) and a “calculation unit configured to calculate a smooth muscle cell (SMC) score” (independent claim 27 at b)), and also (regarding dependent claim 28) an “output unit configured to output prognosis”. While the text of the disclosure references/recites all of the system components – see, e.g., paragraphs 92-97 and 121 – and indicates what they are intended to do (measure/calculate/output) – there is no guidance provided as to what these required “units” actually are. With regard to the drawings, these provide examples of data/results produced via Applicant’s methods, and one may presume that well-known materials employed in such methods (such as a microarray employed in collecting reported data [e.g., Figure 3A and paragraph 136) are a type of “measurement unit”; however, no description of such a “measurement unit” has been provided. Further, while one of skill in the art would conclude – based on the disclosure of well-known types of expression analysis and of the use of well-known tools such as R in statistical analysis (paragraphs 85-86) – that a general purpose computer may function as a “calculation unit”, again the disclosure (including the drawings) fails to actually describe what meets the requirements of a “calculation unit” embraced by the claims. The same is true of the “output unit”, which is referenced (paragraphs 95-97) in terms of what it may potentially do, but never described in such a way that one of skill in the art is apprised as to what it is. Accordingly, as the disclosure fails to disclose any reduction to practice of a system as claimed, and does not provide guidance in any of words, structures, figures, diagrams, etc. describing the claimed system or any of the units thereof noted above, Applicant’s disclosure does not adequately describe, and does not establish possession of, the invention of the present claims.
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) 27-28 and 30-31 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Bagaev et al (US 2018/0358132 A1 [13 Dec 2018]; cited herein).
Bagaev et al disclose systems and methods for identifying cancer treatments from normalized biomarker scores (see the entire reference and particularly, e.g., the Title and paragraphs 8-32). It is noted that Bagaev et al describe their systems and methods as “prognostic” in allowing for prediction of therapy efficacy (see, e.g., paragraph 140)
With particular regard to a) of claim 27, Bagaev et al teach that their methods and systems encompass a variety of embodiments allowing for obtaining expression level data, including via techniques that correspond to measurements as disclosed in the specification, e.g., via the use of a nucleic acid microarray to measure nucleic acids (see paragraphs 126-137, particularly paragraph 133); further, Bagaev et al disclose use of such systems/system components in measuring such levels in patient samples (see, e.g., paragraphs 89-90 and 108-124). With regard to the elected species of expression of TAGLN, Bagaev et al teach that their systems measure TAGLN; see paragraph 139, Table 2, paragraph 304, Tables 4-5. Thus, Bagaev et al teach a system including a “measurement unit” configured to measure TAGLN in a biological sample isolated from a subject (and for the purpose of predicting cancer prognosis), at least to the extent that the claim language is presently understood.
With regard to b) of claim 27, Bagaev et al teach that their systems may be, e.g., computer systems that calculate a “normalized score” for each biomarker of interest, from which may further be calculated a ‘therapy score” indicating “predicted response” (which again is a type of prognosis); see, e.g., the Abstract and paragraphs 18-20 and 24-32. As Applicant’s specification discloses normalizing expression as an embodiment at least potentially encompassed by the invention (see the rejection under 35 USC 112(b) above), and particularly given that the elected species is directed to expression of a single gene (i.e., the claims do not require the use of multiple genes to produce a score), the systems of Bagaev et al – which are disclosed as including/using a computer processor n producing normalized expression scores, as well as in calculating therapy prognostic scores, etc. - meet the requirements of the “calculation unit” of the claims, to the extent that they are presently understood. With regard to the recitation in the claim of a “smooth muscle cell (SMC) score”, it is noted that this term is not defined as requiring any particular calculations, and that the elected invention requires only the single gene TAGLN, such that the scores taught by Bagaev et al meet the present requirements of the claims for a score that is a SMC score.
With regard to the recitation of a “diagnostic system for predicting prognosis of cancer”, it is reiterated that Bagaev et al teach a system for predicting a particular type of cancer prognosis (therapy response), which system encompasses measurement of the elected species TAGLN and calculation of a “therapy score”, such that the systems of Bagaev et al meet the requirement of being a “diagnostic system for predicting prognosis of cancer”.
Bagaev et al thus anticipate claim 27.
With further regard to dependent claim 28, Bagaev et al teach that their systems may comprise the output of information, including of a “normalized biomarker score” and “therapy score” to a user in a graphical user interface (GUI) (see, e.g., paragraph 8, 10, 12, 14, 18-32); this meets the requirements of the claim with respect to an “output unit to output prognosis of cancer”.
Regarding claim 30, Bagaev et al teach that their systems function with regard to stomach cancer, i.e., gastric cancer, including various sample types from subjects with such cancer (including stomach adenocarcinoma); see paragraphs 107, 110, and 146); Bagaev et al thus teach a system “for predicting prognosis of” gastric/stomach cancer (it is noted that the claims under consideration are directed to a “system” requiring the “units” recited in the claims, such that the claims do not require performing method steps with regard to particular sample types, etc.).
Regarding claim 31, it is reiterated that, e.g., Bagaev et al teach use of a microarray for measuring mRNA expression levels, i.e., a “measuring unit” comprising oligonucleotides meeting the requirements of the claim; it is further noted that Bagaev et al disclose other techniques employing primers/probes that may be interpreted as employing a “measurement unit” using probes/primers (e.g., hybridization probes employed with a Southern blot, PCR primers employed within a tube or microtiter dish during PCR, etc.) (see paragraphs 133-137).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 29 is rejected under 35 U.S.C. 103 as being unpatentable over Bagaev et al (US 2018/0358132 A1 [13 Dec 2018]; cited herein) in view of Zhao et al (World J. Gastroenterol 21(1):112-123 [Jan 2015]; cited herein) and/or Yashiro et al (Cancer Research 74(19:Suppl. 1, Abstract No. 3863 [Oct 2014]; cited herein).
With regard to independent claim 27, from which claim 29 depends, Bagaev et al disclose systems and methods for identifying cancer treatments from normalized biomarker scores (see the entire reference and particularly, e.g., the Title and paragraphs 8-32). It is noted that Bagaev et al describe their systems and methods as “prognostic” in allowing for prediction of therapy efficacy (see, e.g., paragraph 140)
With particular regard to a) of claim 27, Bagaev et al teach that their methods and systems encompass a variety of embodiments allowing for obtaining expression level data, including via techniques that correspond to measurements as disclosed in the specification, e.g., via the use of a nucleic acid microarray to measure nucleic acids (see paragraphs 126-137, particularly paragraph 133); further, Bagaev et al disclose use of such systems/system components in measuring such levels in patient samples (see, e.g., paragraphs 89-90 and 108-124). With regard to the elected species of expression of TAGLN, Bagaev et al teach that their systems measure TAGLN; see paragraph 139, Table 2, paragraph 304, Tables 4-5. Thus, Bagaev et al teach a system including a “measurement unit” configured to measure TAGLN in a biological sample isolated from a subject (and for the purpose of predicting cancer prognosis), at least to the extent that the claim language is presently understood.
With regard to b) of claim 27, Bagaev et al teach that their systems may be, e.g., computer systems that calculate a “normalized score” for each biomarker of interest, from which may further be calculated a ‘therapy score” indicating “predicted response” (which again is a type of prognosis); see, e.g., the Abstract and paragraphs 18-20 and 24-32. As Applicant’s specification discloses normalizing expression as an embodiment at least potentially encompassed by the invention (see the rejection under 35 USC 112(b) above), and particularly given that the elected species is directed to expression of a single gene (i.e., the claims do not require the use of multiple genes to produce a score), the systems of Bagaev et al – which are disclosed as including/using a computer processor n producing normalized expression scores, as well as in calculating therapy prognostic scores, etc. - meet the requirements of the “calculation unit” of the claims, to the extent that they are presently understood. With regard to the recitation in the claim of a “smooth muscle cell (SMC) score”, it is noted that this term is not defined as requiring any particular calculations, and that the elected invention requires only the single gene TAGLN, such that the scores taught by Bagaev et al meet the present requirements of the claims for a score that is a SMC score.
With regard to the recitation of a “diagnostic system for predicting prognosis of cancer”, it is reiterated that Bagaev et al teach a system for predicting a particular type of cancer prognosis (therapy response), which system encompasses measurement of the elected species TAGLN and calculation of a “therapy score”, such that the systems of Bagaev et al meet the requirement of being a “diagnostic system for predicting prognosis of cancer”.
With particular regard to the elected species of “gastric cancer”, Bagaev et al also teach that their systems function with regard to stomach cancer, i.e., gastric cancer, including various sample types from subjects with such cancer (including stomach adenocarcinoma); see paragraphs 107, 110, and 146); Bagaev et al thus teach a system “for predicting prognosis of” gastric/stomach cancer (it is noted that the claims under consideration are directed to a “system” requiring the “units” recited in the claims, such that the claims do not require performing method steps with regard to particular sample types, etc.). It is also noted that such cancer inherently meets the requirement of being “malignant” (and it is reiterated that the requirement for “malignant cancer” is indefinite for the reasons given above).
However, Bagaev et al fail to teach the limitation of a cancer (and particularly the elected “gastric cancer’) that has poor prognosis and “stem cell properties”, as set forth in dependent claim 29.
Zhao et al teach that human primer tumors often containing self-renewing
“cancer stem cells” (CSCs) (see entire reference, particularly the discussion of the “Cancer Stem Cell Hypothesis” on page 113), and that multiple types of gastric stem cells (GSCs) are associated with stomach/gastric cancer (see entire reference, particularly pages 115-116) and are associated with recurrence (i.e., poor prognosis) (see page 118).
Yashiro et al teach that CSCs “are known to display stem cell properties, “stemness”, the ability to sustain self-renewal”, and are implicated in tumor growth and metastasis in gastric cancer (see entire Abstract).
In view of the teachings of Zhao et al and/or Yashiro et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have prepared (and used) a diagnostic system “for predicting prognosis of” cancer, including gastric cancer, as taught by Bagaev et al, particularly with respect to and targeting gastric cancers known to be associated with a poor prognosis and having stem cell properties, as taught by Zhao et al and/or Yashiro et al. The teachings of Zhao et al and Yashiro et al, whether considered individually or in combination, establish that at last some gastric cancers are known to exhibit the properties set forth in the claim, and further that such gastric cancers exhibit more aggressive features. Accordingly, given Bagaev et al’s teachings that their system may function in predicting a particular type of cancer prognosis (therapy response), an ordinary artisan would have been motivated to have targeted the system of Bagaev et al to diagnosis/prognosis of gastric cancers as taught by Zhao et al and/or Yashiro et al simply for the benefit of aiding in identifying therapy response for such more aggressive cancers (and thereby improving the likelihood of more appropriately treating a subject/patient having such cancer(s)).
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 27-31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Initially, it is reiterated that the claims are indefinite for the reasons given above, and it is unclear what features characterize the “measurement unit” and “calculation unit” set forth as components of a “diagnostic system” in claim 27. As the claim recites a “calculation unit configured to calculate a smooth muscle cell (SMC) score based on” an expression level or levels, in the interest of compact prosecution, the claims are interpreted as at least potentially being directed to mathematical operations/calculations required to normalize gene expression levels and/or produce a “score” derived therefrom (although it is acknowledged that particular calculations/equations/etc. do not presently appear in the claims).
Independent claim 27 recite(s) a “calculation unit configured to calculate a smooth muscle cell (SMC) score based on” gene expression levels, which levels were “measured by” a recited “measurement unit”. As already noted, the claims are indefinite, and appear to potentially encompass, e.g., a microarray employed in measuring expression, and a general purpose computer or calculator employed to calculate normalized expression levels or a score derived therefrom, etc. Such calculations are a type of mathematical operation – i.e., an abstract idea – and the claims recite nothing further that could be considered as applying such a calculated score into a practical application/implementation. The claim(s) also do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the use together of materials such as microarrays in measuring gene expression and a general purpose computer or calculator in performing calculations such as normalization, scores, etc., employing expression data was well-understood, routine, and conventional in the art as of Applicant’s effective filing date (see, e.g., Bagaev et al, cited and discussed above). With further regard to dependent claim 28, various types of “output units” employed in combination with materials encompassed by claim 27 – e.g., a processor, a GUI, etc. – were also clearly well-known in the prior art before Applicant’s effective filing date (see again, e.g., Bagaev et al). Regarding claims 29-30, these claims recite further characteristics of cancers for which a prognosis may be obtained via the system of Bagaev et al, but do not further limit the actual characteristics of the claimed system in any manner resulting in a practical application or something “significantly more” than a JE. Regarding claim 31, the inclusion of probes/primers in a “measurement unit” for gene expression measurement relates to data gathering (i.e., insignificant extrasolution activity) rather than any type of application/implementation of a JE, and was also clearly well-understood, routine, and conventional before Applicant’s effective filing date. Accordingly, none of claims 27-31 is currently directed to patent eligible subject matter.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. While it is reiterated that Bagaev et al disclose a system meeting all requirements of independent claim 27 with regard to the elected species of TAGLN and gastric cancer, there are also relevant several prior art references teaching associations between TAGLN expression and gastric cancer, including, e.g., Yu et al’s disclosure of performing QRT-PCR of TAGLN RNA isolated from gastric carcinoma tissue samples (BMC Cell Biology 14:17 [2013]; cited in IDS), and the data analysis taught by Liu et al (J. Transl. Med. 18:201 [14 May 2020]; cited herein) and Nation et al (Journal of Computational Biology 28(10):985 [28 Sept 2021]; cited herein).
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
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