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
Status of the Claims
Claims 1-2, 6-12, 15-21 and 32 are pending. Claims 1-2 and 9 are the subject of this FINAL Office Action. Claims 6-8, 10-12, 15-21 and 32 are withdrawn.
New Grounds of Rejections - 35 USC § 112- Indefiniteness
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.
Claims 1-2 and 9 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 pre-AIA the applicant regards as the invention.
Claim 1 is again confusing. Simply put, it is unclear what is “secondary bone marrow involvement.” The specification never uses this phrase. Nor is this phrase common in the art as far as the Examiner can determine. Further, Applicants state in their Reply that “[t]his amendment clarifies the claimed subject matter to correspond to the pathological condition expressly described in the specification” such that “the invention relates to the assessment of bone marrow damage and involvement associated with malignant solid tissue cancers through the analysis of circulating erythroblasts and their ploidy characteristics.” However, this statement is inconsistent with the claimed “secondary bone marrow involvement,” which does not mention cancer. Thus, in light of the evidence of record, the claimed invention is so unclear that any application of prior art would require speculation.
To the extent Applicants intend cancer, at best bone marrow can be “secondary” in the sense that another cancer metastasizes to bone marrow. The specification describes a metastatic breast cancer patient with bone metastasis (Example 4). Erythroblasts were enriched, then “subjected to fixation and perforation using the permeabilization solution 2 according to the manufacturers instructions and stained for fluorescence microscopy analysis using anti-CD45PE (ebioscience), anti-CD71FITC, anti-Ep-CamSB650 (ebioscience), a-VimentinFITC (ebioscience) and anti-pan-CKPerCPCy5 (ebioscience)” (Example 1). Eventually, the sample was “loaded into one well of a specialized 384-well plate suitable for high resolution image recording at 40x magnification using the Operetta system (PerkinElmar) recording a bright field channel, and channels for UV, green, yellow, orange and red fluorescence light emission”, then “Columbus analysis software served as screening and image analysis tool. Marker positive cells included EpCam, CD71, cytokeratin and Vimentin and were identified by a cell-like round formation in case of membrane staining in congruency with bright field morphology, positive Hoechst staining in the absence of the typical ring formation as consequence of positive CD45PE staining throughout the emission light spectrum from 520 nm till 650 nm.” Example 2 explains the “Biomarker Type Classification by Morphology” based on this data. Example 3 explains “Healthy donor tests were conducted to assess cut-off values for abnormality with respect to given cells types listed in [Example 2].” This assay is applied to the metastatic breast cancer patient with bone metastasis in Example 4; and other diseases in Examples 5-7. Applicants are encouraged to claim this specific assay with specific thresholds of Tables 3-4.
It is also unclear if “frequency of aberrant erythroblasts” is separate from ploidy determination and determination of (i)-(viii). Claim 1 now recites “the step of determining the presence and frequency of aberrant erythroblasts in the subject's bodily fluid sample,” then proceeds to define “said determination comprises determining the ploidy of said erythroblasts and the potential-presence of at least one of [(i)-(viii)].” In other words, it seems that “determining the presence and frequency of aberrant erythroblasts” is defined as “determining the ploidy of said erythroblasts and the potential-presence of at least one of [(i)-(viii)].” However, ploidy determination does not determine the frequency of aberrant erythroblasts,” nor do (i)-(viii). Thus, it is unclear how frequency is determined, and whether it is a separate determination from ploidy determination and (i)-(viii).
New Grounds of Rejection - 35 USC § 112 – Written Description
The following is a quotation 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.
Claims 1-2 and 9 rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain 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, at the time the application was filed, had possession of the full scope of the claimed invention.
The specification fails to demonstrate possession of the genus of “pathologic status of a subject’s bone marrow.” Claim 1 states “A method for detecting circulating erythroblasts in a subject’s bodily fluid sample for assessing a pathologic status of a subject's bone marrow.” The specification only discloses one specific pathologic status which “is malignant solid tissue cancer, more preferably non-invasive solid tissue cancer in the presence of mild or no bone marrow damage” (para. 0037; see also Examples). Yet, it also broadly discloses “[t]he term ‘pathologic status in a subject's bone marrow’ as used herein relates to a disease-state or pre-disease-state in the bone marrow tissue of a subject” (para. 0075). In light of the broad statement versus the specific examples, the specification fails to demonstrate possession of the broad any pathologic status.
Further, the only examples are in human subjects. No other subjects (e.g. mice, monkeys, etc.) are disclosed.
Finally, the specification actually discloses a method of classifying tumor stage using bone marrow damage assessment (Examples). This bone marrow damage assessment is performed using erythroblast ploidy status determined by morphological analysis, and distinguishing from CTCs using CD44, CD45, CD71, GPA, cytokeratin and EpCam markers (Table 1). Then, using this information, an EB classification calculation is performed (Tables 3-4, 6, 8, 10 & 12). Applicants are encouraged to amend the claims accordingly.
Further, the specification never describes or mentions “secondary bone marrow involvement.”
New Grounds of Rejection - 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 1-2 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Specifically, under Alice step 1, the claims clearly involve a method which includes a judicial exception, specifically the natural correlation between erythroblast ploidy and a pathologic status, or the natural phenomenon of erythroblast ploidy in bone marrow pathologic status (see Spec., para. 0010).
In fact, under Step 2A, there is simply no integration of the JE into anything else. Claims 1-2 and 9 simply state that “pathologic status in a subject’s bone marrow” is determined by assessing ploidy of an erythroblast, and the presence of (i)-(viii). This is the JE itself.
Even if (i)-(viii) somehow were not part of the JE, yet determining “potential presence” of these things does not integrate the JE in any way. It merely says to detect other characteristics of the erythroblasts, or natural phenomenon. Nothing is done with this determination.
Finally, under step 2A, no additional elements other than the JE are present. Even if the “determinations” somehow were interpreted as assays, yet even here, determining ploidy is routine. See Anticipation rejection, below. To the extent the specification only discloses morphological analysis, yet this, too is routine (Spec., paras. 0096-0107).
In sum, the claims amount to the announcement of a JE and the instruction to apply it. This is not patent eligible subject matter.
Applicants argue that “the amended claims recite a specific method that utilizes defined marker combinations and morphological and ploidy characteristics of circulating erythroblasts to determine the probability or degree of bone marrow involvement associated with secondary bone marrow involvement.” This is inaccurate. The claims do not recite a specific method. Rather, the claims recite a generic concept at a high level of generality: detect presence and frequency erythroblasts in bone marrow using generic ploidy status determination (any assay or technique) and one of the eight listed natural phenomenon (using any assay or technique). This is the opposite of specific.
Applicants further argue that “[t]he claims do not require that any underlying disease be diagnosed” because “the claims are directed to a practical application involving the detection, characterization, and assessment of specific cellular features and their frequencies in a bodily fluid sample, including comparison to predefined thresholds indicative of bone marrow involvement.” Again, this is inaccurate. The claim does not require comparison to predefined thresholds indicative of bone marrow involvement. Instead, the claim merely states that generic aberrant erythroblast frequency exceeding generic threshold conditions are generically “indicative” of generic “pathological status.” In fact, this is a mere re-statement of the natural phenomenon itself in the language of a threshold being “indicative” of the natural phenomenon. And Applicants’ statements that no “underlying disease be diagnosed” is not complete. In fact, Applicants attempt to sneak the “underlying disease” in via the mere “indicative” frequency data because it is indicative of “pathological status.” A pathology is a disease.
Contrary to Applicants’ arguments, the claims fail to “integrate any alleged natural phenomenon into a specific, practical application,” in part because the added language is not in fact a limitation, rather a suggestion with no specific step taken after the “indicative” status. This “indicative” status merely flows from the generic steps of determining the JE of ploidy status and one of the other natural phenomena among the eight listed. The claim merely recognizes that data has certain generic characteristics. There is not integration into any application (e.g. treatment), much less any specific thresholds, data or applications; nor any novel assays, applications or thresholds.
New Grounds of Rejections - 35 USC § 102
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 –
(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 1-2 and 9 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by KAPUR (US 20080138809).
Based on the broad description of “pathologic status,” and using any ploidy and any erythroblasts (e.g. fNRBCs), the claims are anticipated. It is also noted that ploidy status encompasses increased ploidy (e.g. trisomy, aneuploidy, etc.). Finally, the breadth of determining ploidy status encompasses any technique.
The claim amendment merely states that the determination is indicative of a pathological status. No actual step is taken. Thus, the amendment does not change the scope of the claim.
As to claims 1-2 and 4, KAPUR teaches detecting aneuploidy in blood sample fNRBCs using sequencing or PCR (paras. 0054 & 0104, Examples), along with CD44, CD45, CD71, GPA, cytokeratin and EpCam markers (para. 0070).
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 Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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, Gary Benzion can be reached at (571) 272-0782. 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.
/AARON A PRIEST/Primary Examiner, Art Unit 1681
Prosecution Insights