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 .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group II, claims 13-26 and species: IGFBP-3, antisense nucleotide, colorectal cancer, in situ hybridization, and enzyme-linked immunosorbent assay (ELISA) in the reply filed 02/20/2026 is acknowledged.
Claims 1-12, 27 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims. Election was made in the reply filed 02/20/2026.
Claims 13-26 are now under consideration in the instant Office Action.
Claim Objections
Claims 13-26 are objected to because of the following informalities: the instant claim does not explain the acronym “OPN”, “POSTN”, or “IGFBP-3” at their first iteration. The acronyms must be fully spelled out prior to its first iteration, after which point it may be used in place of the term it acronymizes. Appropriate correction is required.
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 13-26 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.
Instant claim 13 recites that the claimed method “provides information for predicting therapeutic responsiveness…”. This renders the claim unclear because the type of “information” is not described in the claims. The dependent claims also fail to provide any tangible metrics for which this information is to be considered against, or the nature of such information (e.g., a baseline mRNA expression level value). Additionally, the instant claims also refer to a broad category of “cancer patients”, and it is unclear who is encompassed within this larger group of individuals. The dependent claims 14-26 fail to remedy this deficiency and thus, are also rejected.
Instant claim 18 recites that the cancer immunotherapy is an anti-PD-L1 antibody. The instant claims do not recite a structure or name of the antibody. As such, the claim is unclear because the identity of the antibody is not described in the claim.
Instant claim 19 recites vague criteria regarding the future treatment plan of the patient based upon the “patient’s therapeutic responsiveness to the cancer immunotherapy” that is determined. The claim is vague and indefinite because it does not provide the criteria or experimental values for which future treatment plans are to be based upon. As written, there is no boundary or criteria that the claims are bound by.
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 14-16 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. Claim 13 recites that the expression level of mRNA or proteins of one or more genes is selected from the group “consisting of” OPN, POSTN, and IGFBP-3, which indicates a narrow scope limited to the genes recited in the claim. Dependent claims 14-16 refers to the genes with “comprising of” language, which broadens the scope in a dependent claim to encompassing not only the genes that are recited in the claim, but more. 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 § 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 13-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claims recites a method for providing information for predicting therapeutic responsiveness of a cancer patient to a cancer immunotherapy by measuring an expression level of mRNA or protein from the group consisting of OPN, POSTN, and IGFBP-3 and evaluating the patient’s therapeutic responsiveness to the cancer immunotherapy. This judicial exception is not integrated into a practical application because all of these products are naturally occurring. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is towards products that are no different from the products found in nature.
The subject matter eligibility under 35 U.S.C. 101 of natural products (i.e., whether the claimed product is a non-naturally occurring product of human ingenuity that is markedly different from naturally occurring products) was confirmed by the U.S. Supreme Court decisions including Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. _, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013), and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101 USPQ2d 1961 (2012). "[L]aws of nature, natural phenomena, and abstract ideas" are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. __, __ (2010) (slip op., at 5). "Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work." Gottschalkv. Benson, 409 U. S. 63, 67 (1972).
In brief, in Prometheus, a method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder is the focus. This method comprises a) administering 6-thioguanine to patients and b) determining the level of 6-thioguanine in the patients and c) correlate the level of 6-thioguanine, i.e. a certain level/red blood cells, with the decision whether a need for increase or decrease the amount of 6-thioguanine treatment in said patients.
In Prometheus, the Court found that "[i]f a law of nature is not patentable, neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Additionally, "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law". Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at __ (slip op., at 14) ("[T]he prohibition against patenting abstract ideas 'cannot be circumvented by’..., adding 'insignificant post-solution activity'" (quoting Diehr, supra, at 191-192)).
The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
Thus, if the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
In the instant case, based upon an analysis with respect to the claims as a whole, claims 13-26 are determined to be directed to judicial exception without significantly more. The rationale for this determination is explained below in view of controlling legal precedent set forth in 2014 Interim Guidance on Patent Subject Matter Eligibility (79 FR 74618) dated December 16, 2014 and 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
The instant claims 13-26 encompass a product. (Step 1: Yes).
Next, Step 2, is the two-part analysis from Alice Corp. (also called the Mayo test) to determine whether the claim is directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions). (In Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) the Supreme Court sets forth a two-step test for determining patent eligibility. First, determine if the claims encompass a judicial exception (a natural phenomenon/law of nature/abstract idea). If so, then ask whether the remaining elements/steps, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to ‘“transform the nature of the claim’ into a patent-eligible application.” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility. Id. at 2355. In the recent Myriad v Ambry case, the CAFC found claims (drawn to methods comprising obtaining tissue samples, analyzing sequences of cDNA and comparing germline sequences of a gene to wild-type sequences) to encompass the abstract mental processes of ‘comparing’ and ‘analyzing’. Recitation of specific techniques (in Myriad claims 7 and 8 further recited hybridization and PCR) were deemed not “enough” to make the claims patent-eligible since the claims contained no otherwise new process. The elements/steps recited in addition to the judicial exception did nothing more than spell out what practitioners already knew). The instant claims encompass measuring a naturally occurring protein or mRNA expression level that occurs while the patient has cancer, and thus are a judicial exception. The products are naturally occurring proteins as a result of a natural correlation, which, as evidenced by the claims and the specification as filed and the prior art, Guan et al. (in IDS filed 10/24/2025), as discussed below, are present naturally and thus a judicial exception (Step 2A/1: Yes). Next, prong two of Step 2A requires identifying whether there are 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. “Integration in to a practical application” requires an additional element or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such as the claim is more than a drafting effort designed to monopolize the exception. In the instant case, the claims do not recite any additional elements to integrate the judicial exception into a practical application because all the claims involve a natural product that results after a natural correlation. The instant claims call for measuring an expression level of mRNA or protein level of a gene obtained from a biological sample obtained from a cancer patient that is screened or evaluated for certain in order to determine prognosis or therapeutic efficacy. (Step 2A/2: No). The second step is determining if the claims recite or involve judicial exceptions, such as laws of nature, natural phenomena, or natural products. In this case, the claims call for specific products that do not structurally change the instantly claimed substance, they only specifically call out a natural correlation using biomarkers to describe and observe the natural correlation. The instant specification does not teach anything beyond measuring the claimed products that result from the natural correlation. The instant claims fail to include any limitations which would distinguish the claimed products from those which occur in nature since they are towards an intended use that does not change or effect the structure or function of the claimed products; it simply measures and observes them. The fact that the instant invention pertains to a natural correlation using biomarkers to describe and observe the natural correlation does not mitigate the fact that it is a simply observing a natural event. It is considered routine and conventional in the art to observe and measure mRNA expression levels in order to monitor changes in disease state. Breaking bonds of amino acids (isolation) is not considered markedly different under the natural product rejection. In the absence of the hand of man, naturally occurring products are considered non-statutory subject matter. Specifically, the claim, as written, do not sufficiently distinguish over the proteins that exist naturally because the claims do not particularly point out any non-naturally occurring differences between the claimed products and the naturally occurring products.
The instant claims read on a natural product because it comprises naturally occurring components that are not markedly different from the naturally occurring products. Isolating the products does not significantly change it structure or function. There are no steps that change this from a natural product, except the act of screening for certain characteristics which again does not affect the natural product. The instant claims do not recite any elements in addition to the natural products that impose meaningful limits on the claim scope and would substantially foreclose others from using these natural products. The intended use of this composition does not further limit or change the basic structure of these naturally occurring products. The composition does not improve in any way their natural functioning. They serve the ends nature originally provided and act quite independently of any effort of the patentee. See Myriad, 133 S. Ct. at 2117.
The instant invention pertains to a natural correlation using biomarkers to describe and observe a natural correlation and does not differ from what is found in nature.
Note that the recited products cannot add significantly more to satisfy step 2B since the composition fails to integrate the products in a practical application since the claimed products are known to occur in nature. In the final step it must be determined if the claim as a whole amounts to something significantly more than the judicial exception. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Claims 13-26 fail to include any limitations which would distinguish the claimed proteins from those which occur in nature since they all still encompass embodiments that read on natural products. In the absence of the hand of man, naturally occurring products are considered non-statutory subject matter. (Step 2B: No).
Thus, for reasons fully explained above, claims 13-26 do not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
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 13-26 are rejected under 35 U.S.C. 103 as being unpatentable over Guan et al. (WO 2019090263 A1, in IDS filed 10/24/2025), in view of Carbone et al. (in IDS filed 05/12/2023), Zhang et al. (in IDS filed 05/12/2023), and Baker et al. (US 8,632,980 B2, in instant PTO-892).
Guan et al. teaches diagnostic methods, therapeutic methods, and compositions for the treatment of cancer (e.g., … , a colorectal cancer, …). The invention is based, at least in part, on the discovery that expression levels of one or more biomarkers described herein in a sample from an individual having cancer can be used in methods of identifying an individual having a cancer who may benefit with an anti-cancer therapy that includes an immunotherapy (e.g., a PD-L1 axis binding antagonist such as an anti-PD-L1 antibody (e.g., atezolizumab)) and a suppressive stromal antagonist (e.g., a TGF-β antagonist), …, [or] methods for assessing a response or monitoring the response of an individual to treatment with an anti-cancer therapy that includes an immunotherapy (e.g., a PD-L1 axis binding antagonist such as an anti-PD-L1 antibody (e.g., atezolizumab)) and a suppressive stromal antagonist (e.g., a TGF-β antagonist), and related kits, anti-cancer therapies, and uses, see Abstract. Guan et al. also teaches that the anti-PD-L1 antibody is MDX-1 106 (nivolumab). This meets the limitations of instant claim 13 wherein a diagnostic method is taught for measuring the expression level of mRNA following cancer immunotherapy.
However, Guan et al. does not teach the specific gene expression marker for osteopontin (OPN). Carbone et al. remedies this deficiency.
Carbone et al. teaches that the baseline expression serum levels of osteopontin (OPN) predicts the response to treatment with nivolumab (an anti-PD-1 antibody) in patients with non-small cell lung cancer, and the expression of OPN protein is measured by ELISA (see the abstract, lines 1-9 in the left column on page 451, lines 1- 10 in the left column on page 455 and figure 3). This meets the limitations of instant claim 13 wherein a method of providing information on the therapeutic effectiveness includes measuring the expression of OPN in a cancer patient, instant claim 14 wherein the gene comprises OPN, instant claims 17 and 18 wherein the cancer immunotherapy is an antibody that inhibits the binding between PD-L1 and PD-1, and instant claim 26 wherein the expression level of the protein is measured by ELISA.
However, Guan et al. and Carbone et al. do not teach the specific gene expression markers for periostin (POSTN) in instant claims 15-16 and 21-22. Zhang et al. remedies this deficiency.
Zhang et al. teaches that “serum periostin levels were significantly higher in non–small cell lung cancer patients, and it was related significantly to bone metastasis (p = 0.021). Serum periostin of 65 non–small cell lung cancer patients were detected before and after two cycles of chemotherapy. The patients with and without periostin response had significant difference in objective response to chemotherapy (p = 0.001). For the 122 non–small cell lung cancer patients, the median progression-free survival was 5 months. Zhang et al. summarizes that “serum periostin was elevated in advanced non–small cell lung cancer patients. Baseline periostin and periostin responses appeared to be reliable surrogate markers to predict chemotherapy response and survival in patients with advanced non–small cell lung cancer”, see Abstract. This meets the limitations of instant claim 15-16 and 21-22 wherein the method comprises evaluating the expression levels of OPN and POSTN.
However, Guan et al., Carbone et al., and Zhang et al. do not teach the specific gene expression markers for IGFBP-3. Baker et al. remedies this deficiency.
Baker et al. teaches the use of “gene sets useful in assessing prognosis and/or predicting the response of cancer, e.g. colorectal cancer to chemotherapy. In addition, the invention relates to a clinically validated cancer test, e.g. colorectal test, for assessment of prognosis and/or prediction of patient response to chemotherapy, using expression analysis”, see Abstract. Baker et al. teaches a particular “method of predicting the likelihood of positive response to treatment with chemotherapy of a subject diagnosed with cancer involving determining the normalized expression level of at least one gene listed in Table 5 or its expression product in a tumor sample obtained from said subject”, with one of the genes listed in the Table being “IGFBP3, IGFBP5, IGFBP7”, wherein the overexpression of said gene indicates that said subject is predicted to have a decreased likelihood of a positive clinical response to the chemotherapy, …, or a gene co-expressed with one or more of said genes, is negatively correlated with an increased likelihood of a positive response to treatment with chemotherapy; and generating a report comprising the score, see Summary. Baker et al. teaches that the expression level of mRNA is measured by either Northern blotting or in situ hybridization, see General Description. This meets the limitations of instant claim 15 wherein the method comprises evaluating the expression levels of OPN, POSTN, and IGFBP-3, instant claims 19-20 wherein the expression level is used as an assessment of prognosis and/or prediction of patient response to chemotherapy, instant claims 21-24 wherein a “low” or decreased level of protein or gene expression is determined after treatment with a cancer immunotherapy, and instant claim 25 wherein the mRNA expression level is determined via in situ hybridization.
It would be obvious at the time of the instant invention to use the diagnostic method taught by Guan et al., which is a method that tracks the expression level of proteins correlated with prognosis in solid cancers, with the various biomarkers taught by Carbone et al., Zhang et al., and Baker et al., which each teach about the change in protein expression in OPN, POSTN, and IGFBP-3 following cancer immunotherapy in a subject as a means of measuring prognosis following treatment. One would be motivated to combine the diagnostic methods with the various biomarkers with the expectation of monitoring the prognosis of cancer in a subject based on determining protein level expressions before, during, and after treatments to test the effectiveness of a cancer immunotherapy and plan treatments accordingly.
Therefore, claims 13-26 are rejected as obvious over Guan et al., Carbone et al., Zhang et al., and Baker et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
Prosecution Insights