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 .
Election/Restrictions
Applicant's election with traverse of (1) a pluripotent stem cell; (2) CVD; (3) cardiomyocytes; and (4) abnormal migration in the reply filed on 3/17/2026 is acknowledged. The traversal is on the ground(s) that the examiner must allow a reasonable number of species to be covered by the claims at this stage wherein 3 species is a reasonable number. Applicant further argues that no claims should be withdrawn at this stage.
The species election requirement has been revisited and the requirement is withdrawn.
Accordingly, claims 1-15 and 25-29 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/30/2023 has been considered by the examiner.
Specification
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.
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 1-15 and 25-29 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) (claim 1 and 29) recite(s) “identifying a plurality of mutation genomic mutations in a plurality cells from a subject, done by comparing the genomic sequence of the subject with a genetic disease with a healthy subject;” and “comparing the stem cell during its differentiation to a stem cell from a healthy subject; and identifying a phenotype of the stem cell from the subject with the genetic disease that is different from the phenotype of the stem cell from the healthy subject.” These steps belong to mental process category of the abstract idea because they can be done in human mind. This judicial exception is not integrated into a practical application because there is no limitation directed to how to use the abstract idea following the last identification step. The only other step for the claimed method is obtaining a stem cell from the subject and induce differentiation of said cell, which is mere data gathering, for the identification of a phenotype. Therefore, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Regarding claims 25 and 26, the further step is also directed to an abstract idea because identifying a time point and cell type may be performed in human mind.
Regarding claim 28, the claim recites the treating, comparing and identifying are automated. However, this limitation is highly general because there is no specific automation process being claimed.
For reason discussed above, the claimed invention of claims 1-15 and 25-29 are not eligible under 101.
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.
Claims 3, 6-8 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.
Regarding claim 3, the recitation of “wherein the stem cell is an embryonic stem cell” renders the claim indefinite because embryonic stem cell can only be obtained from an embryo, not a subject already diagnosed with a genetic disease.
Claim 6 recites the limitation "the cardiovascular disease" in line 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitation "the respiratory disease" in line 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the musculoskeletal disease" in line 1-2. There is insufficient antecedent basis for this limitation in the claim.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4, 5, 9, 26-28 is/are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Rubin (WO 2020/118158, IDS).
Rubin teaches a method of combining genome sequencing, electronic health records (EHRs) and induced pluripotent stem cell biology together in a way to allow for identifying, stratifying and treating these patients. Rubin demonstrates the viability of integrating these three technologies through an exploration of how variants known to lead to increased risk of disease result in detectable and relatable phenotypes in vivo and in vitro (page 5, paragraph [0024]). Rubin teaches EHR systems may store multiple electronic health records including sequencing data obtained from a biological sample of a patient, and may include a list of mutations at certain locations (paragraph 0045]). Following classification output of a disease, a caregiver, provider or researcher will take the information and harvest stem cells from the patient and differentiate them into mature, differentiated cells, wherein the stem cells may be reprogrammed into iPS cells, or other types of stem cells such as adult stem cells or cord blood stem cells may be harvested cells (paragraph [0049]). Rubin teaches that the stem cells may be differentiated into all types of tissues from all germ layers according to known protocols, which includes neuronal, cardiac and hepatic organoid or tissues (paragraph [0050]). Rubin teaches that the differentiated cells may be subjected to different types of assays to identify the phenotype of the differentiated cell and identify any abnormal or disease phenotypes, wherein the results may indicate one or more maladies, abnormalities or other defects that indicate the mechanism of disease in a patient (paragraph [0051). Rubin gives an example of identifying a genomic mutation in LRRK2 variants patients with Parkinson’s Disease (PD) with controls lacking any known LRRK2 coding variants, harvesting iPSC cells from the patient and differentiating said cells to identify a diseased phenotype from the cell (paragraph [0072]-[0074]). The teaching from Rubin thus anticipates the claimed method of claims 1, 2, 4, 5, 9, 26 and 27.
Regarding claim 28, Rubin teaches “the processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more programs to perform actions by operating on input data and generating output” (paragraph [00114]), which meets the limitation of “automated.”
Claim(s) 1, 2, 4, 5, 25, 26, 28 and 29 is/are rejected under 35 U.S.C. 102(a1) as being anticipated by Nevin et al (IDS).
Nevin et al. teach a method of modeling the mutational and phenotypic landscapes of Pelizaeus-Merzbacher Disease (PMD) with human iPSC-derived oligodendrocytes (title). Nevin et al. teach identifying genetic mutation in PLP1 gene from 12 patients, and the identifying is done by comparing the genomic sequence of the subject with the genetic disease with control ((Table 3), page 622, 1st col., 4th paragraph), wherein two of the patient are pediatric subject aged 4 and 12 (page 622, 1st col., last paragraph). Nevin et al. teach obtaining iPSC cells from the subject, and inducing differentiation of said iPSC into OPC over a 90 day time course and identifying a phenotypic defect for the oligodendrocyte (Figure 3 and legend, and Figure 4 and legend). The teaching from Nevin et al. anticipates the claimed invention of claims 1, 2, 4, 5 and 29.
Regarding claim 25 and 26, Nevin et al. teach identifying the time point and cell type during the differentiation of the stem cell when the genetic disease emerges (Figure 3B-3G and legend).
Regarding claim 28, Nevin et al. teach processes such as live cell imaging of differentiated OPCs for phenotypic analysis, “they were automatically imaged every 10 min for the next 60 hr,” (page 620, 2nd col., 2nd paragraph) which meets the limitation of automated.
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.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rubin.
The teaching from Rubin has been discussed above. However, Rubin does not specifically teach differentiating the iPSC into a motor neuron.
For the method taught by Rubin, it encompasses many different types of genetic disease including spinal muscular atrophy (SMA, page 11, paragraph [0034], line 10). It would have been obvious to an ordinary skilled in the art to recognize that motor neuron defects are involved in SMA, thus differentiating iPSC into motor neuron to identify phenotypic abnormality in said cell would have been obvious regarding this specific disorder. Therefore, the claimed invention would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rubin (cited above), in view of Sun (US 2013/0029866).
The teaching from Rubin has been discussed above.
However, Rubin does not specifically teach the phenotype of the differentiated cell is abnormal migration in cardiomyocytes, abnormal sarcomere in cardiomyocyte, abnormal calcium influx in a cardiomyocyte, abnormal contraction in cardiomyocyte or abnormal electrophysiology in cardiomyocyte (claims 11-15).
Sun teaches a method of differentiating iPS cells into cardiomyocytes for use in analysis (abstract). Sun teaches in vitro cell cultures of disease relevant cardiomyocytes differentiated from iPS cells comprising at least one allele encoding a mutation associated with a cardiac disease (paragraph [0012]). Sun teaches a method of determining the phenotypic activity of said cardiomyocytes including calcium transient amplitude, intracellular Ca+ level, cell size contractile force production, beating rates, sarcomeric actinin distribution (paragraph [0014]).
It would have been obvious to an ordinary skilled in the art that different phenotype of cardiomyocytes are associated with specific cardiovascular disease may be modeled in iPS cell culture in vitro as taught by Sun et al. It would have been obvious to an ordinary skilled in the art when performing the method taught by Rubin with regard to cardiovascular disease to identifying relevant phenotype such as abnormal migration in cardiomyocytes, abnormal sarcomere in cardiomyocyte, abnormal calcium influx in a cardiomyocyte, abnormal contraction in cardiomyocyte or abnormal electrophysiology in cardiomyocyte as claimed in claims 11-15 because Sun et al. teach such method of determining those specific phenotype following obtaining iPS cells from patients. The ordinary skilled in the art would have reasonable expectation of success to practice the method taught by Rubin and identifying different phenotypes in cardiomyocytes following combined teaching from Rubin and Sun. Therefore, the claimed invention of claims 11-15 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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, Jennifer Dunston can be reached at 571-272-2916. 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.
/CELINE X QIAN/Primary Examiner, Art Unit 1637
Prosecution Insights