Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
OBJECTION
2. Claims 1, 6, 7, 16, and 17 are objected to because of the following informality: the word ‘of’ is missing between ‘level’ and ‘GPR179’. Correction is required.
NON-PRIOR ART REJECTIONS
3. 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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon or correlation without significantly more. The claims recite a natural correlation between expression of three RNAs or proteins, and differentiation between a malignant tumor and a non-malignant tumor. This judicial exception is not integrated into a practical application because data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only active, physical steps are providing a biological sample and determining the level of RNA or protein corresponding to a particular gene or genes, which were routine and conventional in the prior art, as evidenced by either of Zhang et al. (US 2014/0024552; see paragraph 0132) or Zeillinger et al. (US 2013/0303400; see paragraphs 0189-0190). Claims 14-20 require an additional step of treating with chemotherapy, radiotherapy, or surgery, but these claims are also subject to this rejection because this treatment involves a high level of generality, and the current eligibility guidelines state that treatment at a high level of generality does not amount to significantly more than the judicial exception.
4. Claims 1-20 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 claims contain 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.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 1 12, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the ad, and (8) the breadth of the claims.”
(1) the quantity of experimentation necessary: given the limited experimentation disclosed in the specification, mostly involving an animal model and cell lines, a great deal of undue experimentation would be required to practice the claimed method of differentiating a malignant tumor from a non-malignant tumor by measuring the level of TTR, DUOX2, and/or GPR179 RNA or protein in a biological sample from a mammal, especially a human. The only data in the specification that pertains to patients involves tissue sections from only three patients, and analysis is only qualitative (degree of staining); further, results with DUOX2 were inconclusive. Based on the limited studies presented, the skilled artisan would not be enabled to practice a properly validated diagnostic method using level of any one of the recited RNAs or proteins to statistically correlate with any type of tumor using any type of biological sample from a mammal or human patient. To validate such a method would require undue experimentation using a significant number of mammals or humans, including various sample types such as serum, and extensive statistical analysis. The claims cover both methods of measuring level of RNA and protein, and the limited data in the specification only relates to protein detection. As known to one of ordinary skill in the art, levels of RNA and protein corresponding to any particular gene do not necessarily correlate in any given biological system. Thus, not only is the specification insufficient to validate any diagnostic test regarding proteins, but no data whatsoever is presented regarding RNAs.
(2) the amount of direction or guidance presented: for the reasons noted above, the specification at best indicates that TTR, DUOX2, and GPR179 might serve as useful biomarkers in the future with respect to differentiating LMS from UFs.
(3) the presence or absence of working examples: as noted above, the specification only provides working examples using cell lines, an animal model, and a few tissue sections.
(4) the nature of the invention: the invention relates to diagnostic methods of differentiating a malignant tumor from a non-malignant tumor by measuring one or more of three particular RNA or protein biomarkers.
(5) the state of the prior art: the prior art teaches some diagnostic methods correlating expression of certain RNA or protein biomarkers with certain cancers and other diseases.
(6) the relative skill of those in the art: the level of skill in the art is deemed to be high.
(7) the predictability or unpredictability of the art: methods of determining which RNAs or proteins serve as reliable biomarkers for various cancers and other diseases are highly unpredictable.
(8) the breadth of the claims: the claims are broadly drawn, encompassing any possible malignant tumor type, any possible type of biological sample, and both RNA and protein biomarkers corresponding to TTR, DUOX2, and GPR179.
Based on the above considerations, it is concluded that undue experimentation would be required to carry out the claimed methods using any possible malignant tumor type, any possible type of biological sample, and both RNA and protein biomarkers corresponding to TTR, DUOX2, and GPR179.
PRIOR ART REJECTION
5. 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.
6. 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.
Claims 1-3, 6, 8-14, 16, and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by either of Zeillinger (cited above in paragraph 3) or Zhang (cited above in paragraph 3).
Regarding independent claim 1, Zeillinger discloses a method comprising providing a biological sample from a mammal, determining in the sample a level of transthyretin (TTR) RNA or protein, comparing the level with a control, and determining that a tumor (ovarian) is malignant based on a difference in the sample and control level. See paragraphs 0007 and 0167-0192.
Regarding independent claim 1, Zhang discloses a method comprising providing a biological sample from a mammal, determining in the sample a level of transthyretin (TTR) RNA or protein, comparing the level with a control, and determining that a tumor (ovarian) is malignant based on a difference in the sample and control level. See paragraphs 0124-0138.
Regarding claim 2, Zeillinger and Zhang disclose distinguishing a benign tumor (see paragraphs 0189 and 0132, respectively).
Regarding claim 3, Zeillinger and Zhang disclose using serum as a sample (see paragraphs 0007 and 0012, respectively).
Regarding claims 6 and 16, Zeillinger and Zhang disclose that TTR is higher in the sample versus control (see paragraphs 0188-0192 and 0132, respectively).
Regarding claims 8 and 18, Zeillinger discloses detecting TTR RNA (see paragraph 0188).
Regarding claims 9 and 19, Zhang discloses detecting TTR protein (see paragraph 0132).
Regarding claim 10, Zeillinger and Zhang disclose that differentiation if pre-operative (see paragraph 0004 and 0124, respectively).
Regarding claim 11, Zeillinger discloses detecting proteins by mass spectrometry (see paragraph 0007).
Regarding claim 12, Zhang discloses detecting proteins by ELISA (see paragraphs 0129).
Regarding claims 13 and 20, Zeillinger and Zhang disclose testing a human female (see paragraph 0168 and 0125, respectively).
Regarding claims 14, Zeillinger and Zhang disclose treating a patient (see paragraphs 0163-0164 and 0121, respectively).
The claimed methods cannot be distinguished from the methods of Zeillinger or Zhang.
CONCLUSION
7. No claims are allowable.
8. The following are made of record by the Office as references of interest as disclosing the use of TTR or transthyretin as a biomarker for various cancers: Juhl et al. (US 2007/0184499), Fung et al. (US 2007/0054329), Addis et al. (US 2013/0078642), Choi et al. (US 2017/0212119), and Munroe et al. (US 2016/0109455).
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KENNETH R HORLICK whose telephone number is (571)272-0784. The examiner can normally be reached Mon. - Thurs. 8:30 - 6:30.
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02/19/26
/KENNETH R HORLICK/ Primary Examiner, Art Unit 1681