DETAILED ACTION
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 .
This action is in response to papers filed 7/15/2025.
Applicant’s election without traverse of Group II and the species of protein, MFS and HLA-DR in the reply filed on 11/20/2023 is acknowledged. It is noted that “protein” species is not required for the pending claims and has such has been withdrawn.
Claims 6-11, 13-18 are pending. Claims 1-5 and 12 have been cancelled.
Claims 14-15 and 17-18 are withdrawn based upon the species election.
The following rejections for claims 6-11, 13, 16 are maintained or modified necessitated by amendment with response to arguments follows where applicable.
This action is FINAL.
Modified 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.
Claims 13, 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for detecting HLA-DR and MFS does not reasonably provide enablement for diagnosis of sarcoidosis. 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 or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, 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 art, and (8) the breadth of the claims.”
The nature of the invention and breadth of claims
Claims 13 and 16 are drawn to correlating “lack of up regulation” to having sarcoidosis and treating. With regard to diagnosis of sarcoidosis, the specification does not provide support for correlation of no regulation or down regulation to diagnosis in any sample from any subject.
The invention is in a class of invention, which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
Guidance in the Specification and working examples
The specification asserts that subject includes humans, veterinary animals, research animals and other animals (p. 17). However, the art (as provided below) teaches that up or down regulation and correlation of disease is population and sample specific. The specification does not provide any guidance as to diagnosis of sarcoidosis and up or down regulation of MFS and HLA-DL in any species or sample.
The specification provides a table which indicates MFS and HLA-DR are up regulated in TB versus Sarcoidosis subjects (p 46). However, the specification does not provide guidance to diagnosis a subject with sarcoidosis based upon regulation.
The unpredictability of the art and the state of the prior art
The art of Cobb et al (Crit Care Med 2002 Vol. 30 p. 2711) teaches the unpredictability in analysis of gene expression in spleen and liver sample from septic mice. Notably, the reference teaches that, when compared to a non-septic sample, the relevant expression profiles of the septic mouse spleen and the septic mouse liver contain different nucleic acids at different levels (Table 1; p.2714, middle col., lns.2-8). As such the art teaches that expression levels of the same nucleic acids in different tissue samples differ. Therefore the art indicates that an association of expression level to a disease in one sample would not be correlative to an association to any other sample type.
Enard et al. (Science 2002 Vol 296 p. 340) teaches that even between closely related species gene expression patterns differ (abstract). Enard et al. teaches that mRNA expression levels are different between humans, chimpanzees, orangutans and rhesus marcques (p. 340 1st column last sentence-2nd column 1st paragraph). Enard et al. teaches that there are a large number of quantitative differences in gene expression in closely related mammals (p. 342 2nd column last paragraph). Therefore the art teaches that even between very closely related mammals there is a divergence of gene expression. As such a correlation of expression and disease in one species would not be directly correlative to any other species without further experimentation. This experimentation would be unpredictable as there is no expectation of success that expression patterns observed in one species would be similar to any other species.
Quantity of Experimentation
The quantity of experimentation in this area is extremely large since there is significant number of parameters that would have to be studied. To practice the invention as broadly as it is claimed, the skilled artisan would be required diagnosis based upon the breadth of the claims, the skilled artisan would be required to perform a number of different samples, species, and controls wherein the would not be a predictable exception of a correlation.
The art teaches that each of these cell types and each species would have different expression of the same gene. As such the correlation in one sample type in one species would not be directly correlative to any other sample type or species. As such to perform experiments on a number of different cell types in a number of different species would require undue experimentation wherein the correlations in each type is unpredictable based upon the teaching in the art and the teaching in the specification.
To use the invention as presented would require a large amount of inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
Conclusion
Thus the applicants have not provided sufficient guidance to enable a skilled artisan to make the claimed invention in a manner reasonably correlated with the scope of the claims because the scope of the claims includes correlations to diagnosis of sarcoidosis and up regulation of MFS and HLA-DL in any sample from any species. Without sufficient guidance, determination of the correlation of genetic expression and tumor is unpredictable and the experimentation left to those skilled in the art is extensive. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to, and the lack of guidance provided in the specification balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
The reply traverses the rejection. A summary of the arguetmsn is provided below with response to arguments following.
The reply asserts that the claims have been amended to “a lack of upregulation” (p. 5). The reply asserts that if the markers are upregulated then it is understood that the patent does not have sarcoidosis (p. 5). The reply asserts that even if there is different levels in different organs that the claims require the same organ analysis (p. 6).
These arguments have been reviewed but have not been found persuasive.
The specification does not provide any guidance for such a diagnosis. The specification provides a table which indicates MFS and HLA-DR are up regulated in TB versus Sarcoidosis subjects (p 46). However, the specification does not provide guidance to diagnosis a subject with sarcoidosis based upon upregulation of these two genes and further, in any mammal or sample type as provided in the rejection above. Furthermore, the amendment to “a lack of upregulation”, includes not only down regulation but also no change in regulation. The specification has not provided that sarcoidosis is diagnosed based upon lack of up regulation. Furhtermore, though the subject and the comparison are drawn to the same sample type, there is no guidance in the specificiaotn that any sample from any mammalian species would provide a predictable correlation of regulation of these two genes and sarcoidosis.
Maintained Claim Rejections - 35 USC § 103
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 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) 6-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over in view of Chibout et al. (US Patent Application Publication 2005/0032062 February 10, 2005 cited previously) in view of Watson et al. (US Patent Application Publication 2003/0007976 January 9, 2003 cited previously) and Zauderer et al (US 20030166277 September 4, 2003).
With regard to claim 6, Chibout et al. teaches a method of obtaining a sample of blood patients with sarcoidosis (para 11). Chibout et al. teaches detection of HLA-DR (para 16). As such Chibout et al. teaches obtaining a blood sample and assaying. However, Chibout et al only teaches HLA-DR, but does not teach a subtype of HLA-DR alpha or MFSs.
With regard to claims 7-8, Chibout et al. teaches a method of using a probe with a detectable label to contact the sample (para 84-85).
However, Chibout et al. does not teach membrane protein of M. tuberculosis.
With regard to claim 6, Watson et al. teaches detection of membrane protein of M. tuberculosis (para 191) in a sample associated skin disorders including sarcoidosis (para 22).
With regard to claim 6, Zauderer et al teaches methods of detection of HLA-DR alpha (para 234) and suggests that this region expression is associated with sarcoidosis (para 207).
With regard to claim 9-11, Chibout et al. teaches obtaining weighted scores of the assayed markers (para 170-172). It would be obvious to one of ordinary skill in the art at the time of the effective filing date to quantify and weigh all markers detected in the assay. The ordinary artisan would have a reasonable expectation of success as the claims only requires obtaining values using known assay methods.
Therefore it would be prima facie at the time of the filing of the invention to modify the method of Chibout et al. to assay known regions associated with sarcoidosis including the membrane protein of M. tuberculosis of Watson et al and HLA DR alpha of Zauderer. The ordinary artisan would have a reasonable expectation of success as Chibout et al. teaches assay techniques for sample analysis for MFS and Zauderer et al. teaches detection of HLA DR alpha and it would be well within the skill of the ordinary artisan to assay these known regions in samples taught by Chibout et al. with the intended result of detecting of known targets.
Response to Arguments
The reply traverses the rejection. A summary of the arguetmsn is provided below with response to arguments following.
The reply asserts that the teaching does not associate HLADR with sarcoidosis generally (p. 7). The reply asserts that Watson only teach treatments but does not provide a correlation of detection of M. tuberculosis and sarcoidosis (p. 7). The reply provides that there is no homology of SEQ ID No. 46 with M. tuberculosis ( p. 8). The reply asserts that with regard to Zauderer that there is no link to treatment of the hyperproliferative disorder in Zauderer and the claim detection assay (p. 8). The reply asserts that the weigher scores of the markers of Chibout are based up percent similarity of amino acid and not quantitating an amount as is claimed (p. 8).
These arguments have been reviewed but have not been found persuasive.
It is noted that claim 56 only requires obtaining a sample from a mammalian subject suspected of having sarcoidosis and assaying for markers. The claims do not require any correlation to sarcoidosis or even the subject has sarcoidosis, but rather “suspected of having sarcoidosis”. The claims do not require that the markers are detected or not detected. Therefore the art as provided above, provide guidance that in a populations that have relationships with sarcoidosis can be assayed. The reply asserts that the teach of Watson does not provide a sequence for M. tuberculosis, however, the claims do not require any particular structure. Rather, the claims require a marker that is considered “membrane protein M. tuberculosis”. As Watson et al. teaches detection of membrane protein of M. tuberculosis (para 191) in a sample associated skin disorders including sarcoidosis (para 22) this would be encompassed by the term “marker are membrane protein M. tuberculosis”. The claims are drawn to detecting markers using an assay, these steps do not preclude the use of amino acid structures. As such the teaching of weighted scores of Chibout would encompass the general teaching in the steps of determining weighted scores.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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, Wu Cheng (Winston) Shen can be reached on 5712723157. 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.
/KATHERINE D SALMON/Primary Examiner, Art Unit 1682