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 .
Priority
Applicant claims a benefit to provisional applications 63/214,176, 63/256,445, and 63/296,250. These applications fail to provide support for the claimed subject matter in the instant application. For example, there is no support for a test or reference thymic map or calculating sub-population ratios or relative cTEC ratios. Provisional application 63/321,142 does provide support in the specification for the instant claims. The filing date for 63/321,142 is 18 March 2022 and therefore this application has a priority date of 18 March 2022.
Status of the Claims
Claims 8, 10, 35-45, 47-50, 53, and 54 are cancelled.
Claims 16, 17, 34, 46, 51, 52, and 55 are withdrawn.
Claims 1-7, 9, and 11-15 are under examination.
Election/Restrictions
Applicant’s election without traverse of: Group I, draw to a method of generating a thymic cell product, as amended, in the reply filed on 19 May 2026 is acknowledged. Applicant also made species of elections and that requirement is withdrawn.
Claims 16, 17, 34, 46, 51, 52, and 55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 19 May 2026.
Claim Objections
Claim 6 is objected to because of the following informalities: the claim recites “is an the iTEC SPR”. Appropriate correction is required.
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 1-7, 9, and 11-15 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.
Claim 1 recites the limitation "the test thymic molecular profile" in part e. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the reference thymic molecular profile" in part e. There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites the limitation cell types that are not recited in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the reference thymus map.” There is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation "the human thymi." There is insufficient antecedent basis for this limitation in the claim.
Claim 1 is indefinite because it is not clear if the method is achieved with the method steps recited. The claim recites a test thymic molecular profile and a reference thymic molecular profile but there is not a step in the claim that creates these profiles or what RNA makes up the profile to create the comparison. Further, the terms cTEC high and cTEC low are used in claim 1 without any reference to how high and low are differentiated. The only reference to these terms in the prior art is in Bautista et al. (2021). Bautista et al. appear to be labeling cells as high or low based on how they map for example in figure 2b. This mapping is also based on molecular profiling that is not present in the claim and also expression levels which is not contemplated by any of the claims. The claims will be examined to require molecular profiling in the interest of compact prosecution.
Claims 2-7, 9, and 11-15 are included in this rejection as they do not overcome the rejection to claim 1.
Claims 4 and 5 recite specific types of cells in relation to the SPR and the SPR in claim 1 appears to be a map of the population of the thymic cells. It is not clear from the claim if all these cell types are required for the analysis in claim 1 or possible cell types, or if applicant is indicating that only one of them is analyzed. The claims will be interpreted to read that only one cell type is required for analysis as claim 6 appears to limit the cell type.
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 1-7, 9, and 11-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon and an abstract idea) without significantly more. The claim(s) recite(s) a method of generating a thymic cell product through comparison of a map of populations of cells to a reference. This judicial exception is not integrated into a practical application based on the reasoning below:
The unpatentability of laws of nature and abstract ideas was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S._,_(2010) (slip op., at 5). “Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U. S. 63, 67 (1972).
Additionally, 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 Inti, 134 S. Ct. 2347, 2354 (2014).
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter? Yes, the claims are directed to methods.
Step 2A, prong 1. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes, where the claims recite a step of analyzing RNA sequenced to generate a test thymic map and comparing the thymic map to a reference thymic map, and identifying a thymic cell product using a ratio, such concepts are abstract ideas; they encompass the mental comparison of data and the correlation of data and information to reach a conclusion.
Step 2A, prong 2. Does the claim recite additional elements that integrate the exception into a practical application? No, the judicial exceptions to which the claims are directed are not integrated into a practical application because the rejected claims do not require any particular practical steps related to identifying a thymic cell product using a ratio that are not considered routine.
Step 2B. Does the claim recite additional elements that amount to significantly more than the judicial exception? No, the claims include practical steps related to the extracting and sequencing of RNA, but the broadly recited steps are properly considered routine and conventional and the claims are not significantly more than the judicial exceptions to which they are directed. The claims also recite the step of generating one or more populations of thymic cells, however, this is not integral to the abstract idea steps. The abstract idea of comparing the test thymic map and the reference thymic map achieve the identification of a population of thymic cells. This method could be achieved by acquiring the cells from existing samples. There is nothing in the claims to indicate how the cells are generated except claim 9 and differentiation from stem cells is how thymic cells are created in the body.
For these reasons, the claims are rejected under 35 USC section 101 as being directed to non-statutory subject matter.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-7 and 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Bautista et al. (Nature Communications, 2021).
Bautista et al. use samples (generated in a human) thymic tissues, extract and sequence RNA from each sample, or population, and analyze the RNA using single-cell RNA-seq. (page 12). Bautista et al. teach that different cell types, or sub-populations, can be mapped to generate a map of the population. (see for example, figure 2b). Baustista et al. teach that the cell populations have different signatures, for example early fetal populations contain early cTEC and the other populations do not. (page 4, left column).
Regarding claim 1 and 3, Bautista et al. does not teach creating a ratio based on a test population to a reference population to identify the test population. However, one of ordinary skill in the art would have been motivated to use the information provided by Bautista et al. as a reference map. Thus, one of ordinary skill in the art would have been motivated to compare a test thymic map, created using the methods taught by Bautista et al., to the reference map created by Bautista et al. to identify the test thymic cell population. Bautista et al. has created the reference map, one of ordinary skill in the art would be motivated to use it to identify populations of cells by comparison or a ratio, the more closely they are aligned (or at 1) they can be identified as that reference population.
Regarding claim 2, Bautista et al. teach the identification of the cell types listed. (see page 2 and figure 2f).
Regarding claims 4, 5, and 6, Bautista et al. teach that specific cell types can be mapped and compared to each other. For example, in figure 3a, two sets of iTEC cells are compared.
Regarding claim 7, Bautista et al. show a map of cTEC high to cTEC low in figure 2b with distinct populations on the map. Therefore, one of ordinary skill in the art would have been motivated by this clear delineation to use cTEC high and cTEC low to compare a test thymic map to a reference thymic map in order to predictably identify a test thymic population as the reference with a ration of 1.
Regarding claim 11, Bautista et al used human samples to generate their reference map. (Pages 11-12).
Regarding claim 12, Bautista et al. teach the samples were from fetal thymic tissues, pediatric tissues, and human adult tissues. (pages 11-12).
Regarding claim 13, Bautista et al. show iTEC heat maps examining for example, IGKC, FOS, and FOSB in figure 3C.
Regarding claim 14, Bautista et al. show cTEC heat maps examining for example, PRSS16 and PSMB11 in figure 2d.
Regarding claim 15, Bautista et al. show corneocyte-like mTEC heat map examining for example, CLDN4, KRT1, and IVL.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bautista et al. as applied to claims 1-7 and 11-15 above, and further in view of Parent et al. (Cell Stem Cell, 2013).
Parent et al. teach a method differentiating hESCs into functional thymic epithelial cells. (see document in general and the differentiation method on page 227).
Therefore, one of ordinary skill in the art would have been motivated to use the method taught by Parent et al. with the method taught by Bautista et al. to confirm the genetic makeup of the newly differentiated cells by comparing them to the reference thymic maps created by Bautista et al.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Baran-Gale et al., Ageing compromises mouse thymus function and remodels epithelial cell differentiation, eLife, 2020.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MINDY G BROWN whose telephone number is (571)270-5605. The examiner can normally be reached Monday -Friday, 9:00 am - 5:00 pm EST.
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/MINDY G BROWN/Patent Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
