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 .
Claim Status
1. Currently claims 1-14 are pending and under consideration.
Priority
2. This application has a priority date of April 28, 2020: The application is a U.S. national stage entry under 35 U.S.C. §371 of PCT International Patent Application No. PCT/EP2021/061085, filed April 28, 2021, which claims priority to European Patent Application No. 20171726.1, filed April 28, 2020.
Information Disclosure Statement
3. The listing 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 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the examiner on form PTO-892 or applicant on form PTO-1449 lists the references, they have not been considered.
4. The information disclosure statement filed 10/25/22 has been considered as to the merits prior to First Action on the Merits.
Specification
5. 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. See page 8 line 7 and page 30 line 7 for example.
Abstract
6. This application does not contain an abstract of the disclosure as required by 37 CFR 1.72(b). An abstract on a separate sheet is required.
Claim Objections
7. Claims 1 and 2 are objected to because of the following informalities: The claims include multiple “and” transition terms. The proper claim format requires a listing of options with a single “and” or multiple detection biomarkers listed in a combination with “and…;” Appropriate correction is required.
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.
8. 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. See claims 12 and 13.
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.
9. Claims 1-14 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.
A. Claim 1 is vague and indefinite because the method appears to conduct two different procedures in a single claim. More specifically, the claim requires a method comprises detecting at least two biomarkers selected from the group consisting of Rho GDP dissociation inhibitor beta (ARHGDIB), alpha-tubulin 4A (TUBA4A), glutathione S-transferase omega (GSTO1), filamin A (FLNA), peroxiredoxin 6 (PRDX6) and cadherin 13 (CDH13) while also being directed to a method that comprises the detection of ARHGDIB and at least one biomarker selected from the group consisting of TUBA4A, GSTO1, FLNA and PRDX6 and CDH13. The claim is ambiguous and does not clearly set forth what method will be conducted. It is suggested that the method is written to read on a single procedure (either detecting at least two biomarkers or the detection of ARHGDIB with at least one biomarker from TUBA4A, GSTO1, FLNA, PRDX6, and CDH13) in order to obviate the rejection. Appropriate correction is required.
B. Regarding claims 9 and 12, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
C. Claim 14 is vague and indefinite because it is a “use” claim without methods steps. As recited the claim reads on “the use of a kit”. However, the intended utility is ambiguous. It is suggested that the actual method steps are written in the claim(s) in order to obviate the rejection.
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.
10. Claims 1-11 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 1-11 are drawn to directing lung cancer via the detection of the presence or absence of various biomarkers. However, the instant specification fails to teach how to achieve the proposed detection, especially when the presence or absence of the intended biomarkers is not clearly set forth. The claims appear to be directed to two different methods.
More specifically, the claim requires a method comprises detecting at least two biomarkers selected from the group consisting of Rho GDP dissociation inhibitor beta (ARHGDIB), alpha-tubulin 4A (TUBA4A), glutathione S-transferase omega (GSTO1), filamin A (FLNA), peroxiredoxin 6 (PRDX6) and cadherin 13 (CDH13) while also being directed to a method that comprises the detection of ARHGDIB and at least one biomarker selected from the group consisting of TUBA4A, GSTO1, FLNA and PRDX6 and CDH13. In one embodiment ARHGDIB is required but in another embodiment the biomarker is not necessarily measured. Accordingly the method requires undue experimentation for one skilled in the art to use the claimed invention with a reasonable expectation of success.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Specification does not identify the critical biomarker combinations that are needed to allow for a differential measurement of lung cancer. The Specification identifies various biomarkers that may be included in the measurement but does not clearly set forth a nexus involving the measurement of only at least two of the biomarkers in lung cancer.
On page 17 of the disclosure the inventors found increased levels TUBA4A, GSTO1, FLNA, PRDX6 and ARHGDIB and decreased levels of CDH13 in biological samples, preferably plasma samples, from lung cancer patients (independently of the lung cancer stage) compared to healthy subjects. But this is not set forth in the instant claims.
In view of the lack of guidance and the complete lack of working examples, it is unpredictable, without a definitive structure, whether a compound has the property of being an marker(s) for lung cancer
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentech, Inc, v. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that:
“[pjatent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”, and that “[tjossing out the mere germ of an idea does not constitute enabling disclosure”.
The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art”, “[I]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement”.
Thus a skilled artisan cannot envision all the contemplated biomarker combination involving at least two biomarkers would be differentially expressed in lung cancer, therefore conception cannot be achieved until reduction to practice has occurred. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention.
Tascilar et al. (Annals of Oncology 10,Suppl. 4:S107-S110, 1999) reports on diagnostic methods in the realm of disease states, however this review article is relevant to Applicants’ claimed invention. It is art known that molecular–based assays are valid tools used in predicting and detecting diseases, however as assessed in the Tascilar review “…these tests should be interpreted with caution…”. and “the genetic changes found in sources other than the pancreas itself (blood, stool) should be evaluated prudently”.
Furthermore, Tockman et al. (Cancer Research 52:2711s-2718s, 1992) teach considerations necessary for a suspected cancer biomarker (intermediate end point marker) to have efficacy and success in a clinical application. Although the reference is drawn to biomarkers for early lung cancer detection, the basic principles taught are clearly applicable to other oncogenic disorders.
Tockman teaches that prior to the successful application of newly described markers, research must validate the markers against acknowledged disease end points, establish quantitative criteria for marker presence/absence and confirm marker predictive value in prospective population trials, see abstract.
Early stage markers of carcinogenesis have clear biological plausibility as markers of preclinical cancer and if validated (emphasis added) can be used for population screening (p. 2713s, column 1). The reference further teaches that once selected, the sensitivity and specificity of the biomarker must be validated to a known (histology/cytology-confirmed) cancer outcome.
The essential element of the validation of an early detection marker is the ability to test the marker on clinical material obtained from subjects monitored in advance of clinical cancer and link those marker results with subsequent histological confirmation of disease. “This irrefutable link between antecedent marker and subsequent acknowledged disease is the essence of a valid intermediate end point [marker]”, see page 2714s, column 1, Biomarker Validation against Acknowledged Disease End Points section.
Clearly, prior to the successful application of newly described markers, markers must be validated against acknowledged disease end points and the marker predictive value must be confirmed in prospective population trials, see page 2716s, column 2, Summary section. Tockman reiterates that the predictability of the art in regards to cancer prognosis and the estimation of life expectancies within a population with a disease or disorder are highly speculative and unpredictable.
The instant disclosure has not addressed the issues taught in the prior art as crucial to the discovery and utility of a biomarker or critical to the discovery of a specific marker.
The nature of the invention- the invention is directed to an unidentified biomarker combinations relative to the claimed method of detecting lung cancer.
The state of the prior art- the prior art of record fails to disclose the particular marker(s) required for the method of detecting lung cancer.
The predictability or lack thereof in the art- there is no predictability based on the instant specification that the biomarkers may or may not be measured in the claimed method. And there is no specificity of the marker binding sites.
The amount of direction or guidance present- appropriate guidance is not provided by the specification for the claimed biomarker(s).
The presence or absence of working examples- working examples are not provided in the specification that exemplify the measurement of only two biomarkers as recited in the claimed method.
The quantity of experimentation necessary- it would require undue amount of experimentation for the skilled artisan to make and use the biomarkers that may or may not be measured in the claimed method.
The relative skill of those in the art-the level of skill in the art is high.
The breadth of the claims- as recited, the instant claims are directed to the measurement of biomarkers that may or may not be measured in the claimed method detecting lung cancer.
While it is not necessary to show working examples for every possible embodiment, there should be sufficient teachings in the specification that would suggest to the skilled artisan that the breadth of the claimed construct(s) having detectable expression as claimed is enabled. This is not the case in the instant specification.
In view of the teachings of In re Wands, 8 USPQ2d 1400, it has been determined that the level of experimentation required to enable the breadth of the claims is undue.
Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966).
While every aspect of a generic claim does not have to be carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention. Genetech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001.
That requirement has not been met in this specification with respect to the detection of lung cancer utilizing only two, three, four, or five of the claimed biomarkers that may or may not be measured in the claimed method. Therefore, in view of the insufficient guidance in the specification, extensive experimentation would be required to enable the claims and to practice the invention as claimed.
Claim Rejections - 35 USC § 103
11. 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.
12. Claim(s) 12-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pastor et al. (Journal of Proteomics, Vol,89, 26 August 2013, pages 227-237) in view of Foster et al. (US Patent No. 4,444,879).
Pastor et al. disclose the measurement of ARHGD1B in lung cancer. 40 biomarkers were analyzed in figure 1. The researchers performed proteomic analysis of several biomarkers including ARHGD1B and found that ARHGD1B was upregulated in in the disease set. Venn diagrams (figure 2) were used to display the differentially expressed proteins in each pathological subgroup studied. Among patients belonging to the LC group, 6 proteins were found to be up-regulated (CTSD, ALDO A, FBP1, ERZ, AKR1B10, TKT) and 1 down-regulated (SELENBP1) as compared to those in the control group, that were not found to be differentially expressed in patients belonging to the COPD or COPD/LC groups.
On the other hand, the LC and LC/COPD groups shared 5 proteins (ALDH3A1, AKR1C3, PKM2, PYGM and PPIA) that were significantly up-regulated compared to the control group, that were not deregulated in the COPD group. Similarly, the COPD and COPD/LC groups shared 4 up-regulated proteins (CAT, PRDX1, PRDX2 and PRDX5) in contrast with the LC group. Finally, the three pathological groups shared 24 deregulated proteins, 17 of them up-regulated (HSP70, TXN, ENO1, AMY1A, AMY2A, ANXA1, ANXA2, ANXA5, CA1, CRP, TPPP3, C3A, GSR, IDH1, SERPINB1, PEBP4, and ARHGDIB), 5 down-regulated (GSTA1, GSTA2, GSTP, LCN2, and UCHL1), and 2 proteins (CAPS 2 and CFL1) down-regulated in the COPD group and up-regulated in the LC and LC/COPD groups as compared to the control group.
While Pastor et al. teach the reagents required by the instant claims; it does not specifically claim the reagents in kit configurations. In other words, the patent fails to recite the reagents as a kit. However, kits are well known embodiments for assay reagents. Foster et al.
(U.S. Patent #4,444,879) describe one example. In their patent kits including the reactant reagents, a microplate, positive controls, negative controls, standards, and instructions are taught. The reagents are compartmentalized or packaged separately for utility. See figure 6, and column 15, lines 10-34.
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 take the detection reagents exemplified by Pastor et al. and format it into a kit because Foster et al. teach that it is convenient to do so and one can enhance sensitivity of a method by providing reagents as a kit.
Further, the reagents in a kit are available in pre-measured amounts, which eliminates the variability that can occur when performing the assay. Kits are also economically beneficial in reagent distribution.
It is also worth noting that the printed matter on instructions merely teaches the use of an existing product, and thus cannot impart patentability. See In re Ngai, 5/13/04, Michel, Gajarsa, Linn, per curiam. In other words the printed matter on the instructions in a kit cannot serve to define the kit over the prior art. See In re Gulack, 217 USPQ (CAFC 1983).
13. For reasons aforementioned, no claims are allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lisa V. Cook whose telephone number is (571) 272-0816. The examiner can normally be reached on Monday - Friday from 9:00 AM - 5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on (571) 270-3503.
Any inquiry of a general nature or relating to the status of this application should be directed to Group TC 1600 whose telephone number is (571) 272-1600.
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Lisa V. Cook
Hoteling
Art Unit 1642
571-272-0816
/LISA V COOK/Primary Examiner, Art Unit 1642