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
Claims 1-20, filed August 10, 2022 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election of Group I, claims 1-6, directed to a method of determining cell members in a tissue of interest; and Applicant’s election of Species as follows:
Species (A): wherein the cell types comprise a unique surface marker or a unique combination of cell surface markers (claim 4); and
Species (B): wherein said tissue is not hepatic tissue (claim 5), in the reply filed December 23, 2025 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of invention has been treated as an election without traverse (MPEP
§ 818.03(a)).
Claims 7-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 3 and 6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 2, 4 and 5 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed August 10, 2022, is a CON of the 35 U.S.C. 371 national stage filing of International Application PCT/IL2021/050161, filed February 10, 2021, which claims the benefit of Isreal patent IL272586, filed February 10, 2020.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Isreal on February 10, 2020. It is noted, however, that applicant has not filed a certified copy of Isreal Patent Application No. 272586 as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on October 12, 2022 and December 10, 2025 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Claim Objections
Claims 1, 2, 4 and 5 are objected to because of the following informalities: Claims 1, 2, 4 and 5 recite a mixture of pronouns including “the” and “said” within each claim, such that for consistency, a single pronoun reciting either “the” or “said” should be used.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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, 2, 4 and 5 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite to the recitation of the term “a tissue” such as recited in claim 1, line 10. There is insufficient antecedent basis for the term “a tissue” in the claim because claim 1, line 1 recites the term “a tissue of interest.”
Claim 4 is indefinite to the recitation of the term “said cell types” such as recited in claim 4, line 1. There is insufficient antecedent basis for the term “said cell types” in the claim because claim 1, lines 5-6 recites the term “known cell types.”
Claim 4 is indefinite to the recitation of the term “cell surface markers” such as recited in claim 4, line 2. There is insufficient antecedent basis for the term “cell surface markers” in the claim because claim 4, lines 1-2 recites the term “a unique surface marker.”
Claim 5 is indefinite to the recitation of the term “said tissue” such as recited in claim 5, line 1. There is insufficient antecedent basis for the term “said tissue” in the claim because claim 1, line 1 recites the term “a tissue of interest.”
Claim 2 is indefinite insofar as it ultimately depends from instant claim 1.
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 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.
Claims 1, 2, 4 and 5 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Kumar et al. (hereinafter “Kumar”) (Cell Reports, 2018, 25, 1458-1468 and e1-e4).
Regarding claims 1, 2, 4 and 5, Kumar teaches the development of an approach to characterize cell-cell communication mediated by ligand-receptor interactions across all cell types in a microenvironment using scRNA-seq data (interpreted as receiving a transcriptome), such that after assigning cell types based on the scRNA-seq data using a decision tree classifier, our approach quantifies potential ligand-receptor interactions between all pairs of cell types based on their gene expression profiles, wherein the approach can assess similarities and differences in cell-cell communications between six syngeneic mouse tumor models (interpreted as cell members that physically interact with one another; interpreting scRNA-Seq data as receiving a transcriptome; cell clusters; cell types; and interacting via receptor ligand interaction, claims 1 and 2) (pg. 1459, col 2, last partial paragraph; and pg. 1460, col 1; first partial paragraph, lines 1-2). Kumar teaches that scRNA-seq was performed on tumors from six treatment-naive syngeneic mouse tumor models including B16-F10 melanoma, EMT6 breast mammary carcinoma, LL2 Lewis lung carcinoma, CT26 colon carcinoma, MC-38 colon carcinoma, and Sa1N fibrosarcoma; two samples per tumor model (interpreted as a tissue of interest, claim 1) (pg. 1460, col 1, last partial paragraph). Kumar teaches that for scRNA-seq of mouse syngeneic tumor models, two mice for each syngeneic model were implanted, resulting in a total of 12 samples, and each mouse tumor was harvested when the tumor size reached 100 – 200 mm, wherein each sample was minced and digested with reagents from Mouse Tumor Dissociation Kit, cells were resuspended at 2x105 cells/mL in PBS-0.04% BSA, and each sample was processed individually and run in technical duplicates (interpreted as cell clusters, claim 1) (pg. e2, Method Details). Kuma teaches t-distributed scholastic neighbor embedding (t-SNE) plots of cells from six syngeneic tumor models show distinct clusters predominantly determined by cell type (interpreted as cell cluster; cell members; and cell type, claim 1) (pg. 1460, Figure 1). Kumar teaches scoring cell-cell interactions using known ligand-receptor interactions (interpreted as accessing a computer readable medium storing a library or a plurality of entries having a predicted transcriptome and a set of identities of known cell type; physically interacting; and ligand-receptor interactions, claims 1 and 2) (pg. 1461, col 2; second full paragraph, Title). Kumar teaches that, having defined cell types, the potential cell-cell interactions were quantified between all cell types present in the tumor micro-environment using a reference list of approximately 1,800 known, literature-supported interactions containing receptor ligand interactions from the chemokine, cytokine, receptor tyrosine kinase (RTK), and tumor necrosis factor (TNF) families and extracellular matrix (ECM)-integrin interactions (Ramilowski et al., 2015), wherein known B7 family member interactions were manually added (Southan et al., 2016) because of their relevance to cancer immunology, such that to identify potential cell-cell interactions that are conserved across the six syngeneic tumor models, each tumor model was screened for cases where both members of a given ligand-receptor interaction are expressed by cell types present within the tumor microenvironment (Figure 2), wherein interactions were scored by calculating the product of average receptor expression and average ligand expression in the respective cell types under examination; and after computing scores for each tumor, the interaction score was averaged across the tumor models to identify conserved interactions (Figure 2), such that approximately 1,500 ligand-receptor pairs were screened after converting to mouse homologs [Human to Mouse Homolog Conversion] and 64 pairwise combinations of cell types; as well as, assessing the statistical significance of each interaction score using a one-sided Wilcoxon rank-sum test and performed Benjamini-Hochberg multiple hypothesis correction, such that all interactions for all identified cell types were computed; and all interactions involving tumor cells were examined, wherein many of the highest-scoring interactions were chemokine interactions, often involving the same receptors including Ccr1, Ccr2, Ccr5, and their shared ligands including Ccl2, Ccl4, and Ccl12 (interpreted as accessing a set of identities of known cell types forming said cell cluster; known cell types; searching the library for an entry having a predicted transcriptome matching; extracting from the entry, a set of identities; and interpreting Ccr1, Ccr2, Ccr5 as cell surface markers, claims 1, 2, 4 and 5) (pg. 1461, col 2, last full paragraph; and last partial paragraph; pg. 1463, col 1, first partial paragraph; and first full paragraph, lines 1-4). Kumar teaches that the approach presented can be used to compare the interaction strengths observed in the tumor with those in control tissue from the same donor, such as nearby tissue of the same type or peripheral blood, such that tumor-specific cell-cell interactions can be identified (interpreted as extracting an entry, and determining the cell members of the cell cluster in the tissue, claim 1) (pg. 1467, col 2, first partial paragraph). Kumar teaches that the approach to quantify ligand-receptor interaction was extended to human metastatic melanoma samples, wherein the association of individual cell-cell interactions with pathophysiological characteristics of the tumor micro-environment were examined (interpreted as not hepatic tissue, claim 5) (pg. 1460, col 1, first partial paragraph).
Kumar meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Claims 1, 2, 4 and 5 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Boisset et al. (hereinafter “Boisset”) (Nature Methods, 2018, 15, 547-553).
Regarding claims 1 and 5, Boisset teaches that to create a cellular interaction network, 727 small interacting bone marrow (BM) structures were manually dissected for a total of 1,728 cells across 18 independent experiments (Methods), and inferring the cell types present in the micro-dissected units by scRNA-seq (Fig. 1a) (interpreted as clusters of cell; receiving a transcriptome; and not hepatic tissue, claims 1 and 5) (pg. 547, col 1; last partial paragraph, lines 7-10). Boisset teaches creating a network of physical interactions in mouse BM allowed us to find two new preferential interactions: promyelocyte/myeloblast–plasma cell interactions and megakaryocyte–mature neutrophil interactions; and building a network of cell interactions in small intestinal crypts using a modified approach that does not require extensive microdissection (interpreted as clusters of cell; receiving a transcriptome; cell members that physically interact; and not hepatic tissue, claims 1 and 5) (pg. 547, col 1; last partial paragraph, lines 15-20). Boisset teaches that the frequency of cells per RaceID2 clusters were compared to label permutation simulations, wherein the sorted cell population contained fewer erythroblasts and eosinophils, whereas handpicked cells contained fewer neutrophils, progenitors, and putative macrophage progenitors (expressing S100a4) (Supplementary Fig. 4c); however, despite these few differences in frequency, the cell types present in the two datasets were similar (interpreted as accessing a computer readable medium; searching the library; and extracting from the entry a corresponding set of identities, claim 1) (pg. 548, col 1, first full paragraph). Boisset teaches preparing cells by isolating BM from femurs and tibias, where small interacting structures were selected by visual inspection under a dissection stereomicroscope, such that the structures can be combinations of cells such as doublets or triplets, or slightly bigger units composed of around 10-20 cells (interpreted as cell clusters; and not hepatic tissue, claims 1 and 5) (pg. 554, col 1; first full paragraph). Boisset teaches that CEL-Seq library preparation, clustering, and differential gene expression, wherein total RNA was prepared according to manufacturer’s instructions; and libraries were sequenced on Illumina HiSeq 2500 and NextSeq500, where sequence reads were mapped (mm10 transcriptome) to both C57BL/6 and CAST/EtJ transcriptomes and quantification of the number of transcripts were performed as previously described including (interpreted as clusters; and accessing a computer readable medium storing a library of entries; searching the library of entries having a predicted transcriptome matching the received transcriptome; and extracting a set of identities, claim 1) (pg. 554, col 1, fifth and sixth full paragraphs).
Regarding claim 2, Boisset teaches that compared with the random model, enrichment for specific interaction between macrophages and a subtype of adult erythroblasts was observed (interpreted as interacting via receptor-ligand interaction, claim 2) (pg. 548, col 2, first full paragraph).
Regarding claim 4, Boisset teaches in Figure 2, the identification of enriched and depleted interactions in the BM: (a) a, t-SNE map of transcriptome similarities with enriched and depleted interactions, wherein nodes represent cluster centers, edges represent inter-cluster interactions, and solid nodes represent intra-cluster interactions (b–d), t-SNE map of transcriptome similarities, with color-coded representation of transcript counts for Beta-s (b), Elane (c), and Retnlg (d), such that Pink edges represent all interactions stemming from cluster 10 (macrophages; b), cluster 16 (plasma cells; c), and cluster 2 (megakaryocytes; d) (interpreted as cell types comprise a unique surface marker, claim 4) (pg. 549, Figure 2).
Boisset meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Conclusion
Claims 1, 2, 4 and 5 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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, Heather Calamita can be reached on (571) 272-2876. 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.
/AMY M BUNKER/Primary Examiner, Art Unit 1684