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 11/26/2025.
Claims 1-6 are pending. The rejections have been maintained as necessitated by amendment with response to arguetmsn following.
This action is FINAL.
Withdrawn Rejections
The 35 USC 112b rejection made in the prior office action is withdrawn based upon amendments to the claims.
Maintained 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 1-6 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-5 are drawn to therapeutic selection comprising obtaining surgical drain fluid, evaluating a biomarker indicative of a therapeutic efficacy against the tumor and selecting a targeted therapy. Claim 6 is drawn to screening patients for efficacy of anticancer therapy comprising obtaining a sample of surgical drain fluid, evaluating a biomarker indicative of a response to therapy, providing a selected therapy based on said biomarker, obtaining a second body fluid sample and evaluating efficacy of the therapy.
Therefore the claims are drawn to a genus of any therapeutic selection or any anticancer therapy in any species. The claims are drawn to any evaluating, which would include any association including expression, mutation, copy number analysis, protein or DNA analysis. Further, the claims are drawn to any biomarker “indicative to therapeutic efficacy” in any species.
The specification does not provide any critical guidelines to evaluating biomarkers nor any description of the biomarkers. The specification has not provided guidance as to the critical structures required for any of the pathways, in any samples from any subjects. The specification does not describe any treatments or anticancer therapies nor how the selection or evaluation are performed for selection.
As shown below, the art teaches that this is a very large genus wherein merely being expressed in one sample is not sufficient to describe the critical features in any other sample.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. However, as discussed above, the specification provides on particular species and does not provide critical structures for the breadth of the claims.
Further, the art, as recited below, teaches that expression of biomarkers differ in different species. However, the specification has not provided identifying characteristics or functional attributes that would distinguish different members of the claimed genus. Rather, the art teaches that changes in the structure of nucleic acids between species can have an effect on expression. 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).
The art of Cobb et al (Crit Care Med 2002 Vol. 30 p. 2711) teaches the 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 the identifying characteristics or functional attributes that would distinguish different members of the claimed genus will differ depending on the sample type.
In the instant case the specification does not provide the skilled artisan with an adequate written description of particular nucleic acids suitable for performing the claimed method as generically encompassed in the claims.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that "Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed." (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.)
Response to Arguments
The reply traverses the rejection. A summary of the arguetmsn is provided below with response to arguetmsn following. The reply asserts that the artisan would be aware of any variations between species and samples and be able to select methods of measurement and selection of therapeutics based upon the teaching of the specification providing biomarker evaluation (p. 4-5). These arguetmsn have been reviewed but have not been found persuasive. Although the artisan skilled in the art can obtain, isolate biomarkers the specification has not described which biomarkers in any species or samples would functionally provide critical guidance for the selection of therapy for a particular outcome. The claims are drawn to any evaluating, which would include any association including expression, mutation, copy number analysis, protein or DNA analysis. Further, the claims are drawn to any biomarker “indicative to therapeutic efficacy” in any species. The specification does not provide any critical guidelines to evaluating biomarkers nor any description of the biomarkers. The specification has not provided guidance as to the critical structures required for any of the pathways, in any samples from any subjects. The specification does not describe any treatments or anticancer therapies nor how the selection or evaluation are performed for selection.
Maintained 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 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is a directed to the judicial exception of natural phenomena of correlation of evaluating a biomarker and selection of therapies without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Note that the unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012).
The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014).
Applicant’s attention is directed to the USPTO January 7, 2019 Revised Patent Subject Matter Eligibility Guidance (i.e., “PEG”) available at URL:
<https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf>.
Regarding Step 1 of the PEG, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims are directed to and recite the natural phenomena of selection of therapies based upon evaluating a biomarker.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the recited correlation by including a step to integrate rather the claims only requires a routine step (as described below) of evaluating a biomarker from a drain fluid. The step of providing a selected therapy and applying the therapeutic steps in claims 3 and 6 are not considered to integrate the judicial exception as these are not specific treatments to integrate, but rather encompass any possible treatment.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The broadly recited method for expression analysis are routine and conventional steps of hybridization or amplification assays.
In Mayo v. Prometheus, the Supreme Court stated: "[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."
Lassig et al. (JAMA Otolaryngol Head Neck Surg 2017 Vol 143 p. 670). teaches obtaining a drain fluid proximal to a tumor (p 5 1st 2 paragraphs). Lassig et al. teaches evaluation of the biomarker and selection of a therapy (p. 5 1st 3 paragraphs and p. 17 last 2 paragraphs).
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the claims do not recite a natural phenomenon (p. 6-7). The reply asserts that the for treatment the inability of cells to survive treatment is not considered a law of nature (p. 7). The reply asserts that the claims further require laboratory instruments and reagents to measure the biomarker in the fluid (p. 7). The reply asserts that the claims are integrated and even if not the analysis of drain fluid is not well understood routine or conventional activity (p. 8). These arguetmsn have been reviewed but have not been found persuasive.
The correlation of the biomarker and the association with therapeutic outcome is considered a naturally occurring phenomena as the data obtained from the biomarker exist in nature. The claims are not drawn to treating with the therapeutic and therefore the treatment of the cells is not considered. Although it is acknowledged that obtaining the surgical drawn fluid and isolating the biomarkers is laboratory steps, these steps are well understood and conventional as it is well known in the art to isolate biomarkers from samples. The specification teaches that these fluids include lymphatic fluid and blood and these sample types are very well known to be used to isolate nucleic acids.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lassig et al. (JAMA Otolaryngol Head Neck Surg 2017 Vol 143 p. 670).
With regard to claim 1, Lassig et al. teaches obtaining a drain fluid proximal to a tumor (p 5 1st 2 paragraphs). Lassig et al. teaches evaluation of the biomarker and selection of a therapy (p. 5 1st 3 paragraphs and p. 17 last 2 paragraphs).
With regard to claim 2, Lassig et al. teaches that the fluid is interstitial fluid (p. 16 3rd paragraph).
Response to Arguments
The reply traverses the rejection. The reply asserts that Lassig does not provide the comparing or selecting step (p. 9). These arguetmsn have been reviewed but have not been found persuasive. Lassig et teaches in the introduction that data regarding tumors positive for hpv can be used to recommend less intense treatment. Further, Lassig et ales that treatment decisions were made based upon tumor evaluation (p. 5). The claims do not require the selection of therapy to be based upon the biomarker comparison.
Claim(s) 1-6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mansfield et al. (US Patent Application Publication 2012/0171694 July 5, 2012).
With regard to claims 1-2, Mansfield et al. teaches a method of obtaining a fluid sample that includes lymph fluid, cerebrospinal fluid (para 30). Mansfield teaches evaluating biomarkers from the fluid samples to detection therapy selection (para 30 and 52).
With regard to claims 3, Mansfield et al. teaches a method of obtaining a fluid sample that includes lymph fluid, cerebrospinal fluid (para 30). Mansfield et al. teaches selecting a therapy and determining an effect (para 52-60).
With regard to claim 4, Mansfield et al. teaches simultaneously multiplexing across samples (para 59),
With regard to claim 5, Mansfield et al teaches that the tumor biopsy is cultured prior to applying (para 31).
With regard to claim 6, Mansfield et al. teaches a method of obtaining a fluid sample that includes lymph fluid, cerebrospinal fluid (para 30). As Mansfield et al. teaches selecting a therapy for cancer and determining an effect (para 52-60). Mansfield et al. teaches measuring the change before and after providing the therapy (para 47-51).
Response to Arguments
The reply traverses the rejection. The reply asserts that Mansfield is towards a generic biomarker assay in blood, serum and plasma for ovarian cancer (p. 9).
These arguments have been reviewed but have not been found persuasive.
The specification has not provided a definition of “surgical drain fluid”. The claims indication that the drain fluid can include cerebrospinal fluid (ss claim 2). Mansfield et al. teaches a method of obtaining a fluid sample that includes lymph fluid, cerebrospinal fluid (para 30). As such the teaching of the sample of Mansfield would be encompassed by the broadest interpretation of “surgical drain fluid” as these can be removed by a needle from the patient.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18087165 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because although ‘165 requires a step of obtaining surgical drain fluid from a surgical site of a tumor removal, this would be encompassed by “obtaining a drain fluid proximal to a tumor”. Further both applications require evaluating biomarkers from this sample to therapeutic efficacy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejections have been maintained with the require that the rejections are held in abeyance.
Claim 6 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of copending Application No. 17947861 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims require obtaining multiple drain fluid samples and evaluating biomarkers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejections have been maintained with the require that the rejections are held in abeyance.
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.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682