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 Group 1, claims 1-10 and 14-17 and the species of graft versus host disease (claim 14) in the reply filed on January 26, 2026 is acknowledged.
The traversal regarding inventions is on the grounds that unity of invention exists between Groups 1-3 because Applicant asserts the office has not indicated that the claims were interpreted in light of the description and that there is a technical relationship which involves the same special technical feature which defines the contribution which the invention makes over the prior art. This is not found persuasive because the examiner was able to provide art which satisfied the limitations of the of the technical feature of a stem cell genetically engineered to overexpress a CEACAM family protein thereby demonstrating that the special technical feature lacks novelty. Therefore a lack of unity exists between the restricted groups.
The traversal regarding species is on the grounds that the examiner’s conclusion that the species are not patentably different based on their distinct disease types and distinct etiologies is insufficient. One of ordinary skill in the art would not be likely to conclude that the species of graft-versus-host disease, inflammatory diseases, autoimmune diseases, and neurodegenerative diseases were obvious variants and would recognize that each distinct disease type would require different fields of search.
The requirement is still deemed proper and is therefore made FINAL.
Claims 19-20 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, and claims 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on January 26, 2026.
Claims 1, 14, and 15 have been amended. Claims 1-10 and 14 are examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/KR2022/000761, filed on January 14, 2022. The instant application claims foreign priority under 35 U.S.C. 119(a)-(d) to Korean Patent Applications KR10-2021-0008386, filed on January 20, 2021, and KR10-2022-0001265, filed on January 5, 2022. Receipt is acknowledged of a certified copy of the foreign patent application in the original language as required by 37 CFR 1.55. The earliest possible priority for the instant application is January 20, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 20, 2023 is in compliance with the provisions of 37 CFR 1.97 and is being considered by the examiner.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
Figure 2 of the Specification does not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the figure legend does not provide shading differences between “no stimulation” and “stimulation conditions” making it difficult to determine between conditions.
Figures 7B & 7E of the Specification do not conform to standards as “readable and reproducible for publication purposes” as set forth in MPEP § 507 (see also 37 CFR 1.84(b)). Specifically, the shading of the figure legends makes it difficult to determine differences between each passage number (see PBMC+PHA in Fig. 7E for example).
Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Objections to the Specification
The disclosure is objected to because of the following informalities: Applicant’s specification contains multiple recitations of “CEACM1” (for example, see Pgs. 12, 28, 40-44, 46) which is considered to be a typographical misspelling of “CEACAM1”. The example locations provided are not intended to be a complete list and it is recommended that Applicant review the full disclosure for other instances. Appropriate correction is required.
The use of the term ReverTraAce (Pg. 32), UltraPure (Pg. 32), Glutamax (Pg. 34) and CellTrace (Pg. 34), which are trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 103
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.
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 1-2, 5-6, 9, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Koh et al. (2019, Biological Function of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 for the Enhancement of Adipose-Derived Stem Cell Survival against Oxidative Stress", Korean J. of Clin. Lab. Sci., 51(4), found in IDS, Google English translation attached) and Yanez et al. (2006, Adipose tissue‐derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft‐versus‐host disease. Stem Cells, 24(11), 2582-2591).
With regard to claim 1, Koh teaches that use of stem cell-based therapies to treat diseases is currently limited by existing drawbacks of the stem cells including their limited proliferative capacity and the low survival rate of stem cells after administration. Additionally, Koh teaches that when administered, stem cells face challenges which limit survival such as oxidative stress and host immunity and that overexpression of anti-apoptotic and antioxidant proteins can increase stem cell viability and survival (Pg. 1, 2nd para.). Further, Koh teaches that CEACAM6, which is considered to reasonably read on a CEACAM family protein, is known to confer antiapoptotic properties and resistance to oxidative stress (Pg. 1, 3rd para.) and that when adipose-derived stem cells (ADSCs) (Pg 2, Cell Culture), which normally do not express CEACAM6 (Pg. 4, section 1), are genetically engineered to express CEACAM6 (Pg. 5, section 2), the ADSCs which overexpress CEACAM6 are protected from cytotoxicity in response to oxidative stress conditions generated by exposure to H2O2 and exhibited reduced apoptosis (Pgs. 5-6, section 3). Koh concludes that overexpression of CEACAM6 in ADSCs maintains cell viability in response to oxidative stress and that overexpression of CEACAM6 could be used to enhance therapeutic efficacy and proliferation of stem cells (Pg. 8, Summary).
Although Koh teaches that stem cells can have widespread use in treatment of many diseases (Pg. 8, Summary) and that ADSCs which have been genetically engineered to overexpress CEACAM6 protect against oxidative stress, which a skilled artisan would recognize is associated with cell damage, Koh is silent as to the use of ADSCs for the treatment of cell-damage related diseases and to administration of a ADSCs to a subject.
Yanez teaches that adipose-derived mesenchymal stem cells can be administered to a subject for the treatment of graft-versus-host disease, which is considered to reasonably read on a cell-damage related disease (Abstract; Pg. 2584, Mouse Model of GVHD; Pg. 2587, right col., 2nd para., Fig. 6, and Table 1).
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to choose the ADSCs with have been genetically engineered to overexpress CEACAM6 and which exhibit increased cell viability as taught by Koh for use in the method of treating of graft-versus-host disease via administration of adipose-derived mesenchymal stem cells as taught by Yanez with a reasonable expectation of success. A skilled artisan would be motived to choose Koh’s ADSCs which overexpress CEACAM6 in the Yanez’s method of treatment of graft-versus-host disease because Koh teaches that the utility of stem cells for the treatment of diseases is currently limited by the fact that stem cells experience limited viability after administration (Pg. 1, 2nd para.) and ADSCs which overexpress CEACAM6 possess increased cell viability. Further, although Yanez’s model is silent as to stem cell viability after administration, Yanez’s treatment method teaches multiple infusions of adipose-derived mesenchymal stem cells spaced 1 week apart (Pg. 2587, right col., 2nd para.; Fig 6) which indicates that multiple administrations of stem cells are required for effective treatment of graft-versus-host disease which could be due to the known viability limitations of stem cells after administration. Thus, one of ordinary skill would have been motivated to combine these teachings in order to produce a more effective stem cell which could be used to treat cell damage related diseases. A skilled artisan would have had a reasonable expectation of success as the teachings of both Koh and Yanez are drawn to use of adipose derived mesenchymal stem cells and teach administration of stem cells for the use in treatment of diseases. Furthermore, Koh teaches the ability of stem cells to be used in transplant medicine (Introduction), while Yanez teaches that graft-versus-host disease constitutes the most frequent complication associated with transplantation (Introduction). Thus, a skilled artisan would have every reason to believe that ADSCs expressing CEACAM6 as taught by Koh could be used in the Yanez’s method of treatment of graft-versus-host disease via administration of ADSCs.
With regard to claim 2, Koh teaches stem cells which overexpress CEACAM6 (Pg 2, Cell Culture; Pg. 4, section 1; Pg. 5, section 2).
With regard to claims 5 and 6, Koh teaches use of ADSCs and that ADSCs are a commonly used type of mesenchymal stem cell (Pg. 1, 1st para.).
v
With regard to claim 14, as detailed above, Yanez teaches use of adipose-derived mesenchymal stem cells in the treatment of graft-versus-host disease (Abstract).
Claims 3-4 and 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Koh and Yanez as applied to claim 1 above, and further in view of Gray-Owen and Blumberg (2006, CEACAM1: contact-dependent control of immunity. Nature Rev. Immunology, 6(6), 433-446).
With regard to claims 3 and 4, as detailed above, the combined teachings of Koh and Yanez teach a method of treating a cell damage-related disease via administration of ADSCs which have been genetically engineered to overexpress a CEACAM family protein, CEACAM6.
While Koh mentions that CEACAM6 belongs to the CEA family (Pg. 6, last para.), is known to be expressed in breast cancer cells, and enhances cell adhesion as well as resistance to apoptosis and oxidative stress (Pg. 1, last para.), Koh does not teach CEACAM1.
Gray-Owen and Blumberg teach that the CEACAM proteins of the CEA family (Pg. 433, left col., 1st para) are involved in the intercellular adhesion and signaling processes related to growth and differentiation of normal and cancer cells and that some CEACAMs also function to modulate immune responses in (Abstract). Gray-Owen and Blumberg teach that CEACAM1 which comprises splice variants including CEACAM1-4L, CEACAM1-4S (Pg. 433, right col., last para. and Fig. 1), CEACAM1-3S and CEACAM1-3L (Pg. 436, right col., 2nd para. and Fig. 1), serves as an inhibitor of T cell activation (Pg. 435, right col, 3rd para.) and functions to control T cell activation in vivo in immune-mediated disease (e.g., graft-versus-host disease) (Pg. 439, left col., last para.).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to choose CEACAM1 (including splice variants CEACAM1-3L, CEACAM-3S, CEACAM1-4L, and CEACAM1-4S) as taught by Gray-Owen and Blumberg in the method of treatment of a graft-versus-host disease using ADSCs which overexpressing a CEACAM family protein as taught by the combination of Koh and Yanez with a reasonable expectation of success. Since Gray-Owen and Blumberg teach that expression of CEACAM1 and variants serve to inhibit T cell activation, particularly in immune-mediated disease, a skilled artisan would have been motivated to choose CEACAM1 (including splice variants CEACAM1-3L, CEACAM-3S, CEACAM1-4L, and CEACAM1-4S) in order to generate stem cells which are less likely to generate immune reactions after administration. A skilled artisan would have a reasonable expectation of success as the combination of Koh and Yanez teaches overexpression of a CEACAM family protein in stem cells which can be administered for the treatment of a cell-damage related disease and Gray-Owen and Blumberg teach that CEACAM family proteins, including CEACAM1, play a role in mediation of immune related diseases, which is considered to reasonably read on a cell-damage related disease.
With regard to claims 7 and 8, as detailed above, the combined teachings of Koh, Yanez, and Gray-Owen and Blumberg teach a method of treating a cell damage-related disease via administration of ADSCs which have been genetically engineered to overexpress a CEACAM family protein, CEACAM1. Gray-Owen and Blumberg teach that CEACAM1 expression serves as an inhibitor of T cell activation (Pg. 435, right col, 3rd para.) and functions to control T cell activation in vivo in immune-mediated disease (e.g., graft-versus-host disease) (Pg. 439, left col., last para.). Gray-Owen and Blumberg teach that CEACAM1-related inhibition precedes expression of the co-inhibitory receptor CTLA-4, which is considered to reasonably read on an immune checkpoint protein, and that both CEACAM1 and CTLA-4 serve to inhibit T cell activation (Pg. 435, right col., 3rd para.).
With regard to claims 9 and 10, directed to “wherein the stem cell is capable of evading the immune response by NK cells”, as stated above, Gray-Owen and Blumberg teach that CEACAM1-related inhibition by expression of CTLA-4, which is also known to be capable of evading the immune responses by NK cells.
In regard to claim 9, MPEP 2111.04 (I) indicates that a “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure” and a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” The examiner has determined that the “wherein” clause of instant claim does not limit the structure of the engineered stem cell, the type of CEACAM transgene, nor does it affect the route of administration of the cells to the patient, as recited in the antecedent claims. Therefore, the language of the instant claim does not provide a limiting effect on the claimed method.
Furthermore, in regard to claims 9 and 10, it is noted that the "wherein the stem cell is capable of … evasion of the immune response by NK cells is caused by a decrease in degranulation activity has an improved in vivo survival" clause does not recite any additional active method steps, but simply states a characterization or conclusion of the results of process step positively recited (e.g. administering). Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to genetically engineer a stem cell to also overexpress CTLA-4 in addition to CEACAM1 with a reasonable expectation of success. Since Gray-Owen and Blumberg teach that CEACAM1 and CTLA-4 function together as coinhibitors of T cell activation, a skilled artisan would have been motivated to overexpress CTLA-4 in addition to CEACAM1 in order to generate stem cells which were better able to avoid T cell activation after transplantation.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631