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 without traverse of Group I, claim 1-12 and 15, in the reply filed on 02/11/2026 is acknowledged.
Claims 16-19, 21, 22, and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/11/2026.
Status of the Claims
Claims 1-12, 15-19, 21-22, and 26 are currently pending.
Claims 16-19, 21-22, and 26 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 13-14, 20, and 23-25 are cancelled.
Claims 1-12 and 15 have been considered on the merits.
Claim Objections
Claim 1 is objected to because of the following informalities: the phrase “CD45RA-memory T cells” needs to be amended to “CD45RA- memory T cells”. A space is required between “CD45RA-“ and “memory” to clearly convey that the cells are CD45RA negative. Appropriate correction is required.
Claim 12 is objected to because of the following informalities: the term “track” in the last line should be amended to “tract”. Appropriate correction is required.
Claim Interpretation
Claim 1 contains the phrase “a method of treating immunocompromised patients suffering from lymphopenia”. The specification contains the following definition for the term “treatment”: “[t]he term ‘treatment’ refers to the medical care given to a patient. It can be, according to the present invention, a prophylactic or pre-emptive treatment for the prevention of the viral infection vulnerable patients, or an active treatment for patients suffering from a viral infection” (pg. 11). Thus, the term treatment is defined by Applicant to include the prevention. However, the claim requires a method of treating immunocompromised patients suffering from lymphopenia, therefore, the method of claim 1 requires lymphopenia to be present and is not claiming a method of preventing lymphopenia from occurring.
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 5-12 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 5 recites the limitation "the CD45RA- CD4+ cells" in lines 2-4. There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites “wherein at least 60% of the CD45RA- CD4+ cells are CD27+”, “wherein at least 5% of the CD45RA-CD4+ cells are CD27-“, and “wherein at least 5% of the CD45RA-CD4+ cells are CD25+” in lines 2-4, which renders the claim indefinite. It is not clear if the population which contains a specified percentage of CD45RA- CD4+ cells are referring to the CD45RA- memory T cells of claim 1, however as written the population of claim 1 does not require that the cells be CD4+. Therefore, it is unclear which population of cells must contain 60% CD27+ expression, 5% CD27- expression and 5% CD25+ expression.
Claim 6 recites the limitation "the CD45RA- CD8+ cells" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites “wherein at least 50% of the CD45RA- CD8+ cells are CD27+”, “wherein at least 10% of the CD45RA-CD8+ cells are CD27-“, in lines 1-2, which renders the claim indefinite. It is not clear if the population which contains a specified percentage of CD45RA- CD8+ cells are referring to the CD45RA- memory T cells of claim 1, however as written the population of claim 1 does not require that the cells be CD8+. Therefore, it is unclear which population of cells must contain 50% CD27+ expression and 10% CD25- expression.
Claim 7 recites the limitation "the CD3+ cells" in lines 2-4. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites “wherein at least 10% of the CD3+ cells are HLADR+”, “wherein at least 0.5% of the CD3+ cells are CD69high+ ”, and “wherein at least 10% of the CD3+ cells are CD25+” in lines 2-3, which renders the claim indefinite. It is not clear if the population which contains a specified percentage of CD3+ cells are referring to the CD45RA- memory T cells of claim 1, however as written the population of claim 1 does not require that the cells be CD3+. Therefore, it is unclear which population of cells must contain 10% HLADR+ expression, 0.5% CD69high+ expression, and 10% CD25+ expression.
Claim 8 recites the limitation "the CD4+ cells" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites “wherein at least 5% of the CD4+ cells are HLADR+”, “wherein at least 0.2% of the CD4+ cells are CD69+ ”, and “wherein at least 20% of the CD4+ cells are CD25+” in lines 2-3, which renders the claim indefinite. It is not clear if the population which contains a specified percentage of CD4+ cells are referring to the CD45RA- memory T cells of claim 1, however as written the population of claim 1 does not require that the cells be CD4+. Therefore, it is unclear which population of cells must contain 5% HLADR+ expression, 0.2% CD69+ expression, and 20% CD25+ expression.
Claim 9 recites the limitation "the CD8+ cells" in lines 1 and 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the CD8high+ cells" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites “wherein at least 5% of the CD8+ cells are HLADR+”, “wherein at least 0.15% of the CD8high+ cells are CD69+”, and “wherein at least 4% of the CD8+ cells are CD25+” in lines 1-3, which renders the claim indefinite. It is not clear if the population which contains a specified percentage of CD8+ cells and CD8high+ cells are referring to the CD45RA- memory T cells of claim 1, however as written the population of claim 1 does not require that the cells be CD8+ nor CD8high+. Therefore, it is unclear which population of cells must contain 5% HLADR+ expression, 0.15% CD69+ expression, and 4% CD25+ expression.
Claim 10 recites the limitation "the CD3+ cells" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the CD4+ cells" in line 3. There is insufficient antecedent basis for this limitation in the claim
Claim 10 recites the limitation "the CD8+ cells" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites “wherein less than 5% of the CD3+ cells are NKG2A+”, “wherein less than 1% of the CD3+ cells are PD1+”, “wherein less than 0.1% of the CD4+ cells are NKG2A+”, “wherein less than 5% of the CD4+ cells are PD1+”, “wherein less than 20% of the CD8+ cells are NKG2A+”, and “wherein less than 5% of the CD8+ cells are PD1+” in lines 1-5, which renders the claim indefinite. It is not clear if the population which contains a specified percentage of CD8+ cells, CD4+ cells, and CD3+ cells are referring to the CD45RA- memory T cells of claim 1, however as written the population of claim 1 does not require that the cells be CD8+, CD4+, nor CD3+. Therefore, it is unclear which population of cells must contain the claimed characteristics.
Claim 11 recites the limitation "the CD3+ cells" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the CD4+ cells" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the CD8+ cells" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites “wherein at least 60% of the CD3+ cells are CCR7+”, “wherein at least 1% of the CD3+ cells are CD103+”, “wherein at least 50% of the CD4+ cells are CCR7+”, “wherein at least 0.5% of the CD4+ cells are CD103+”, “wherein at least 30% of the CD8+ cells are CCR7+”, and “wherein at least 2% of the CD8+ cells are CD103+” in lines 1-5, which renders the claim indefinite. It is not clear if the population which contains a specified percentage of CD8+ cells, CD4+ cells, and CD3+ cells are referring to the CD45RA- memory T cells of claim 1, however as written the population of claim 1 does not require that the cells be CD8+, CD4+, nor CD3+. Therefore, it is unclear which population of cells must contain the claimed characteristics.
Claim 12 recites the limitation "the activation markers" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation "the basal cell population" in line 4. 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.
Claims 1-3 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Basar et al (“Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy”, BioRxiv preprint, posted 09/15/2020).
Regarding claim 1, Basar teaches a cell suspension comprising at least 90% CD45RA- memory T cells (Fig. 1C and description). Basar teaches that the memory T cells are derived from the blood of convalescent patients recovered from an infection with a respiratory pathogen and have specific reactivity against pathogen antigens (pg. 10, Discussion, para 1). Basar teaches SARS-CoV-2 infection is characterized by profound T-lymphopenia associated with a dysregulated/excessive innate response, thought to be the underlying mechanism for acute respiratory distress syndrome (ARDS), the major cause of morbidity and mortality of this virus (pg. 3, para 2). Basar teaches that the adoptive transfer of SARS-CoV-2 T-cells may be a suitable therapeutic strategy for treatment of patients with severe COVID-19 (pg. 12, para 3). Additionally, Basar teaches that their approach allows for cryopreservation and banking of SARS-CoV-2 T-cells, facilitating the rapid identification and selection of viral-specific T cells for ACT based on the most closely HLA-matched third-party donor (pg. 12, para 2). Therefore, Basar meets the limitations of a method of treating an immunocompromised patient suffering from lymphopenia comprising administering the claimed cell suspension of claim 1.
Regarding claim 2, Basar teaches that the T-cells are derived from the blood of convalescent patients recovered from SARS-CoV-2 which have specific reactivity against SARS-CoV-2 pathogen antigens (pg. 10, Discussion, para 1). Additionally, Basar teaches that lymphopenia is induced by SARS-CoV-2 (pg. 3, para 2).
Regarding claim 3, Basar teaches that the T-cells are derived from the blood of convalescent patients recovered from SARS-CoV-2 which have specific reactivity against SARS-CoV-2 pathogen antigens (pg. 10, Discussion, para 1). Additionally, Basar teaches that lymphopenia is induced by SARS-CoV-2 (pg. 3, para 2).
Regarding claim 15, Basar teaches that the cell suspension is to be infused into a patient, which meets the limitations of wherein the cell suspension is administered intravenously (pg. 12, para 1).
Therefore, Basar anticipates the claims.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4-6, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Basar et al (“Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy”, BioRxiv preprint, posted 09/15/2020).
Claim Interpretation: Claim 1 requires that that the CD45RA- memory T cells are derived from the blood of convalescent patients recovered from an infection. Claims 4-6 and 12 limits wherein the cell population has specific percentages of CD or expression markers. Based on the cell population of claim 1 being derived from a patient and there not being any specified step of altering the cells in any way, the specific percentages of the cell population which express the claimed CD markers are being interpreted to ultimately vary based on the blood of the patient who donates. The claims are being interpreted to be met by any teaching or recitation of testing the specific expression of the claimed CD markers of the cell population.
Regarding claims 4-6 and 12, the limitations of the independent claim 1 are taught by Basar above.
Basar does not explicitly teach wherein at least 75% of the CD45RA- cells are CD3+ cells, wherein at least 70% if the CD45RA- CD3+ cells are CD4+ and wherein at least 10% of the CD45RA- CD3+ cells are CD8+ as required by claim 4. Basar does not teach wherein at least 60% of the CD45RA-CD4+ cells are CD27+, wherein at least 5% of the CD45RA-CD4+ cells are CD27- and wherein at least 5% of the CD45RA- CD4+ cells are CD25+ as required by claim 5. Basar does not teach wherein at least 50% of the CD45RA- CD8+ cells are CD27+ and wherein at least 10% of the CD45RA- CD8+ cells are CD27- as required by claim 6. Basar does not teach wherein the expression of activation markers CD69, CD25, HLADR, and/or CD103 is characterized by an increased fold change of at least 1.5 when compared with expression measured in the basal cell population and consequently show an improvement in activation markers and migration capacity to the respiratory tract as required by claim 12.
However, claims 4-6 and 12 are currently being interpreted to be met by any recitation of testing the cell population for the claimed CD markers or expression markers.
Regarding claims 4-6 and 12, Basar does teach testing the expression of CD markers CD3, CD4, CD8, CD27, CD25, and HLA-DR (see Fig. 1A-C and Fig. 1F).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of Basar with the teachings of Basar to test the cell population for expression of CD3, CD4, CD8, CD27, CD25, and HLA-DR to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Basar teaches both the cell population derived from convalescent patients of SARS-CoV-2, and the testing the cell population derived from convalescent patients of SARS-CoV-2 for the cell expression markers: CD3, CD4, CD8, CD27, CD25, and HLA-DR. One of ordinary skill in the art would have a reasonable expectation of success when combining the method of Basar with the expression profiles of Basar because Basar has already taught the successful testing of the cell population, however does not provide exact percentages of the levels of expression as claimed in claims 4-6 and 12.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Basar et al (“Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy”, BioRxiv preprint, posted 09/15/2020), in view of White et al (Nat Rev Immunology, 2018).
Claim Interpretation: Claim 1 requires that that the CD45RA- memory T cells are derived from the blood of convalescent patients recovered from an infection. Claims 7-11 limits wherein the cell population has specific percentages of CD or expression markers. Based on the cell population of claim 1 being derived from a patient and there not being any specified step of altering the cells in any way, the specific percentages of the cell population which express the claimed CD markers are being interpreted to ultimately vary based on the blood of the patient who donates. The claims are being interpreted to be met by any teaching or recitation of testing the specific expression of the claimed CD markers of the cell population.
Regarding claims 7-11, the independent claim is taught by Baser et al above.
Basar does not teach wherein at least 10% of the CD3+ cells are HLADR+, wherein at least 0.5% of the CD3+ cells are CD69high+ and wherein at least 10% of the CD3+ cells are CD25+ as required by claim 7. Basar does not teach wherein at least 5% of the CD4+ cells are HLADR+, wherein at least 0.2% of the CD4+ cells are CD69+ and wherein at least 20% of the CD4+ cells are CD25+ as required by claim 8. Basar does not teach wherein at least 5% of the CD8+ cells are HLADR+, wherein at least 0.15% of the CD8high+ cells are CD69+, and wherein at least 4% of the CD8+ cells are CD25+ as required by claim 9. Basar does not teach wherein less than 5% of the CD3+ cells are NKG2A+, wherein less than 1% of the CD3+ cells are PD1+, wherein less than 0.1% of the CD4+ cells are NKG2A+, wherein less than 5% of the CD4+ cells are PD1+, wherein less than 20% of the CD8+ cells are NKG2A+, and wherein less than 5% of the CD8+ cells are PD1+ as required by claim 10. Basar does not teach wherein at least 60% of the CD3+ cells are CCR7+, wherein at least 1% of the CD3+ cells are CD103+, wherein at least 50% of the CD4+ cells are CCR7+, wherein at least 0.5% of the CD4+ cells are CD103+, wherein at least 30% of the CD8+ cells are CCR7+, and wherein at least 2% of the CD8+ cells are CD103+ as required by claim 11. Basar does not teach wherein the expression of activation markers CD69, CD25, HLADR, and/or CD103 is characterized by an increased fold change of at least 1.5 when compared with expression measured in the basal cell population and consequently show an improvement in activation markers and migration capacity to the respiratory tract as required by claim 12.
However, However, claims 7-12 are currently being interpreted to be met by any recitation of testing the cell population for the claimed CD markers or expression markers.
Regarding claims 7-12, Basar does teach testing the expression of CD markers CD25, HLA-DR, PD1, and CCR7 (see Fig. 1A-C and Fig. 1F).
Basar does not disclose the testing of cell populations for CD69, CD103, and/or NKG2A as required by claims 7-12.
However, White discloses a literature review on the various phenotype profiles of memory T cells for (abstract). White discloses resident memory T cels as typically expressing high levels of CD69 and CD103 (see pg. 17, “Box 1”). Additionally, Human innate memory CD8+ T cells subset are tested and express NKG2A (See table, pg. 21).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of Basar with the phenotypic expression profiles of memory T cells taught by White to test the cell population for expression of CD69, CD103, and/or NKG2A to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because White teaches a review of the phenotypic profiles of memory T cells known in the art and used for characterization of memory T cells (abstract) and Basar teaches the application of similar phenotypes to characterize the specific cell population. One of ordinary skill in the art would have a reasonable expectation of success when combining the method of Basar with the expression profiles of White because Basar has already taught the successful testing of the cell population for expression markers, and White provides information on the expression of additional markers in memory T cell subsets.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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, Peter Paras can be reached at 571-272-4517. 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.
CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632