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 .
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 23 February 2026, which claims 1, 44, and 45 were amended, has been entered.
Claims 1, 44-45, and 53-57 remain under consideration. Applicant’s amendments and arguments have been thoroughly reviewed, and have overcome the following objections/rejections set forth in the prior Office action:
The rejections of claims under 35 USC 112(b) in view of Applicant’s amendments (although it is noted that claims 44-45 and 57 remain rejected under 35 USC 112(b) for the reasons given below);
The rejection of claims 1 and 53-56 under 35 USC 102(a)(1) and 35 USC 102(a)(2) in view of the amendment of claim 1 such that it is directed to a “method of treating cancer in a subject” that concludes with a requirement for one of two different types of “administering”;
The rejection of claim 1 and claims dependent therefrom (claims 53-56) under 35 USC 101, in view of the amendment of claim 1 such that it is directed to a “method of treating cancer in a subject” that concludes with a requirement for one of two different types of “administering” that apply the judicial exception(s) of the claim.
As Applicant’s amendments have overcome all rejections of independent claim 1 and claims dependent therefrom, claim 1 and its dependent claims 53-54 and 56 are allowed (with dependent claim 55 being objected to due to a typographical error as noted below, but otherwise allowable). Claims 44-45 and 57 remain rejected for the reasons given below. Any rejections and/or objections not reiterated in this action have been withdrawn. This action is non-final.
Claim Objections
Claim 55 is objected to because of the following informalities: nivolumab is misspelled “nivomab”. Appropriate correction is required.
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 44-45 and 57 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 44 and 57 are indefinite over the recitation in independent claim 44 of the limitation “at least one primer or probe directly attached to a label that hybridizes to” a recited target (which language appears multiple times in the claims). This language has multiple reasonable interpretations that impart different boundaries on what is claimed; specifically, based on a literal interpretation of the language the claims require a “label that hybridizes to” the recited target, whereas a person of ordinary skill in the art could also reasonably interpret the “that hybridizes to” language as applying to the “at least one oligonucleotide primer or probe”, with any type of label being “directly attached to” the at least one primer/probe. Clarification is therefore required.
Claim 57, which depends from claim 44, is also indefinite over the recitation of the limitation “The method of claim 44, wherein the label is selected from…” because: a) claim 44 is directed to a composition (not a method), such that it is unclear what method is being referenced/required; and b) the reference to “the label” is confusing given the ambiguity noted above, and because more than one label is referenced claim 44 (such that it is unclear what constitutes “the label”).
Independent claim 45 is indefinite over the recitation of the limitation “wherein the first oligonucleotide primer or probe is directly attached to a label that hybridizes to” a recited target (see lines 4-5) and “wherein the oligonucleotide primer or probe is directly attached to a label that hybridizes to” a recited target (see lines 8-9). First, with regard to both instances of this language, as noted above regarding claim 44, the language has multiple reasonable interpretations that impart different boundaries on what is claimed; specifically, based on a literal interpretation of the language the claims require a “label that hybridizes to” the recited target, whereas a person of ordinary skill in the art could also reasonably interpret the “that hybridizes to” language as applying to the referenced “oligonucleotide primer or probe”, with any type of label being “directly attached to” the at least one primer/probe. Second, as the claims previously refer to “at least one” oligonucleotide (first) primer or probe, clear antecedent basis is lacking for the recitation of “the first oligonucleotide primer or probe” (line 5) and “the oligonucleotide primer or probe” (line 8), as the claim does not previously specify any such particular oligonucleotide. Clarification is therefore required.
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.
Claim(s) 44-45 and 57 remain rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Campana et al (US 9,777,332 B2 [Oct. 2017; filed March 2012]; previously cited),
It is reiterated that the present claim language does not make clear the nature of what is actually being claimed, and that a reasonable interpretation of the claims encompasses oligonucleotides to which are directly attached “a label that hybridizes to” the target of the oligonucleotide.
Campana et al disclose generating expression profiles for acute lymphoblastic leukemia (ALL) that include mRNA expression levels established using nucleic acid probes, which profiles include data for genes found to be overexpressed or underexpressed in ALL relative to healthy controls; see entire reference, particularly column 11, line 40-col 12, line 47, Tables 1-2; col 129, line 50-col 132, line 4 (it is noted that the terms “overexpressed” and “underexpressed” are defined at col 8, lines 9-28). Campana et al report that they found both MAP1LC3B and EHMT1 to be underexpressed in ALL (regarding MAP1LC3B, see Table 2 at cols 67-68, bottom half of the page; regarding EHMT1, see Table 2 at cols 103-104, top half of the page). Campana et al teach that a variety of different methods may be employed to achieve expression profiling, including methods in which probe microarrays are used to capture RNA transcripts and assess expression levels; see, e.g., col 110, line 38-col 111, line 18. Campana et al exemplify obtaining their data reported in Table 2 (as well as Table 1) by hybridizing transcripts generated from ALL samples (as well as controls) to Affymetrix HG-U133A oligonucleotide microarrays; see col 136, line 35-col 137, line 35). As such, Campana et al disclose a composition/solid support meeting all requirements of claims 44-45 and 57, and anticipate those claims. Specifically, the Affymetrix arrays taught by Campana et al include attached oligonucleotide probes that hybridize to all captured expression products (including those of MAP1LC3B and EHMT1, as evidenced by Table 2 of Campana et al), while the microarray/solid support as employed by Campana et al - with captured target nucleic acids hybridized to their corresponding probes - meets the requirements for a composition including such transcripts/cDNAs as recited in claim 44 (again see col 136, line 35-col 137, line 35). Regarding the claim language “probe directly attached to a label”, it is reiterated that the claims are indefinite and that a reasonable interpretation of the present claim language in light of the specification includes “labels” that are themselves nucleic acid fragments that hybridize to target sequences (such that the oligonucleotides of Campana et al are sufficient to meet the requirements of the claims). Regarding dependent claim 57, again as discussed above, the claim is indefinite for multiple reasons (including with regard to what is further limited and what label is being referenced, etc.), such that
the claim is rejected for the same reasons that apply to claim 44, from which it depends.
With regard to the preamble and “wherein” language of claims 44-45, it is noted that these recitations do not impart any apparent further requirements applicable to the actual structure of the products being claimed, but rather simply state an intended use for the claimed products that does not result in any structural difference in the claimed product as compared to the prior art product disclosed by Campana et al (see MPEP 2111.02 and 2111.04).
The reply of 23 February 2026 traverses the prior rejection of claims based upon Campana et al on the following grounds.
First, Applicant urges that “a prior disclosure which presents an immense class/list of possibilities does not ‘make available’ a specific member of that class unless the specific member is individually described identified”, and argues that Campana does not meet the requirements for anticipation, particularly as the reference “provides no individualized teaching of MAP1LC3B for predicting response to cancer therapy, nor does it disclose the claimed labelled primer/probe structures” (Reply page 5). Next, Applicant states that “MAP1LC3B was not immediately envisaged or clearly named for any specific utility”, while the inventors have found that MAP1LC3B expression products “are reliable indicators of response to cancer therapy” (Reply page 6). Applicant also urges that “their claims involve prognostic and diagnostic assays for therapy response, which Campana neither teaches nor suggests” (Reply page 6), and argues that the invention “clearly describes that cancers with an elevated level of EHMT2 expression, in combination with a low MAP1LC3B expression level, had a worse overall survival”, with patients with high levels of MAP1LC3B expression having “a significantly longer survival rate after receiving checkpoint inhibitor molecule therapies” (Reply page 6 bridging to page 7).
These arguments have been thoroughly considered but are not persuasive with regard to Applicant’s product claims (it is reiterated that the rejection applied against the method claims has been withdrawn, as indicated above). Regarding the issue of anticipation and the “immense” class taught by Campana et al, it is noted that Applicant’s claims recite the open transitional language “comprising” as one alternative, such that compositions including the recited preferred transcripts and oligonucleotides in combination with numerous other oligonucleotides, transcripts, etc. are embraced by the present claim language. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further, with regard to the recited primer/probe structures, the claims embrace oligonucleotides “attached to a label that hybridizes to” recited target sequences, and Campana et al clearly disclose such oligonucleotides (as discussed in the rejection). Regarding the issue of Campana et al failing to teach MAP1LC3B expression as an indicator of therapy response, and failing to teach or suggest “prognostic and diagnostic assays for therapy response”, the rejected product claims are not required to be employed in such methods, and could clearly be employed in some manner to achieve the objective of “assessing likelihood” of response, etc. As Campana et al teach a product meeting all requirements of the claims as written, they anticipate what is claimed. Finally, regarding the issue of differences in patient survival and therapy response associated with MAP1LC3B and EHMT2 expression levels, the claims under consideration embrace products that are disclosed by Campana et al (particularly given the open transitional language appearing in the claims), and thus this argument is non-persuasive (and as previously noted, the fact that Applicant may have shown particular benefits of specific genes/combinations – e.g., an alleged unexpected property or benefit – cannot overcome a rejection under 35 USC 102(a)(1)/35 USC 102(a)(2)).
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 44-45 and 57 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon/law of nature without significantly more.
Claim 44 recites a composition including two types of oligonucleotide primers/probes and two types of nucleic acid transcripts/cDNAs, while claim 45 recites a solid support comprising two types of immobilized primer/probe. The nucleic acids of these claims are broadly recited, and encompass portions/fragments of naturally occurring nucleic acids present together in a composition or on a support. While it is noted that each of claims 44 and 45 has been amended to state that the primers/probes as claimed are “directed attached to a label that hybridizes to” the target, this encompasses (based on a literal interpretation of the claim language, as discussed above in the rejections of the claims under 35 USC 112(b)) a “label” that is simply a further nucleotide sequence “that hybridizes to” the corresponding target, such that the claims continue to embrace oligonucleotides that are nothing more than fragments of naturally occurring nucleic acids. It is reiterated that the specification defines the term “label” as referring to “any atom or molecule that can be used to provide a detectable and/or quantifiable signal” (paragraph 62 at page 16), and further teaches that a label or marker may be “any radioactive, fluorescent, biological or enzymatic tags or labels of standard use in the art” (paragraph 109 at page 28); thus, the present claim language does not preclude the use of naturally occurring nucleotides that function as a “label”.
Thus, these nucleic acid materials as claimed are not markedly different from their naturally occurring counterparts, nor does their presence together render them markedly different from a product of nature.
With further regard to claims 44 and 47, nothing beyond nucleic acids themselves are required by independent claim 44, such that nothing providing integration into a practical application, or potentially adding something “significantly more” than a judicial exception, is required. Dependent claim 57 as written is further limiting of “the label”, however, the claim is indefinite as noted above, and it is unclear what is being further limited; thus, there is no clear requirement for anything “markedly different” than a naturally occurring nucleic acid, as well as nothing amounting to a practical application, or something “significantly more”, than a JE. It is noted that when the broadest reasonable interpretation of a claim encompasses both statutory and nonstatutory embodiments, the claim is directed to nonstatutory subject matter (see MPEP 2106.03(II)).
Regarding claim 45, while it is again noted that the claim requires oligonucleotides “immobilized” on a support, the term “immobilized” as employed in the application does not necessarily require any alteration of the oligonucleotides that would render them “markedly different”, as this term encompasses, e.g., the fixing of probes to a support “by electrostatic forces, hydrophobic or hydrophilic interactions or Van-der-Waals forces” (see paragraph 62). This amounts to providing the probes on any type of generic support in a manner in which they are not necessarily permanently attached/fixed, with the support constituting a nominal or token extra solution component that is nothing more than an attempt to generally link a product of nature to a particular technological environment. As this type of immobilization of such nucleic acids to generic supports was also well-understood, routine, and conventional before the effective filing date of applicant’s invention, the inclusion of such a support in this manner also fails to add something “significantly more” to the product of nature. The analysis of the limitation “directly attached to a label” discussed above with respect to claim 44 also applies to claim 45. Thus, claims 44-45 and 57 are not directed to patent eligible subject matter.
The reply of 23 February 2026 traverses the prior rejection of these claims under 35 USC 101 on the grounds that the claims require design of a specific primer or probe, and “artificially” attaching the primer/probe to a label in a way that “necessarily involves a chemical manipulation” (Reply page 8). This argument has been thoroughly considered but is not persuasive because the claims cannot be interpreted in the manner upon which Applicant’s arguments rely, and because the claims in fact embrace broad categories of primers/probes in which nucleotide sequences function as a label.
Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Conclusion
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682