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 .
Applicant’s submission filed on June 17, 2026 has been entered and considered. Rejections and/or objections not reiterated from the previous action mailed March 17, 2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 1 has been amended to recite CEACAM 1 as in previously dependent claim 3. Claims 2 and 3 have been canceled. Claims 1, 4-10 and 14 are examined on the merits.
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 was deemed proper and made FINAL in the Office Action dated March 17, 2026.
Claims 19-20 and 24 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, and claims 15-17 were previously withdrawn from further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.
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.
New Claim Rejections - 35 USC § 103
This is a new rejection necessitated by Applicant’s amendment. However, this rejection shares substantial similarity to the rejection as previously set forth in the office action dated March 17, 2026. The following new rejection provides additional interpretation of the claims which is necessitated by Applicant’s amendment in the response filed on June 17, 2026. Any aspect of Applicant’s traversal that pertains to the rejection as newly set forth will be provided following the new statement of rejection.
Claims 1, 4-10, 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) in view of 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) and Gray-Owen and Blumberg (2006, CEACAM1: contact-dependent control of immunity. Nature Rev. Immunology, 6(6), 433-446).
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, a member of the CEA/CEACAM family of proteins, 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 skills would have been motivated to combine these teachings in order to produce a more effective (i.e., viable) 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.
While the combination 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, but are silent as to overexpression of CEACAM1.
Furthermore, 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 5 and 6, Koh teaches use of ADSCs and that ADSCs are a commonly used type of mesenchymal stem cell (Pg. 1, 1st para.).
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.).
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.
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 the 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.").
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).
Response to Arguments
Applicant's arguments filed June 17, 2026 are acknowledged and have been fully considered but they are not persuasive.
Claims 1-2, 5-6, 9 and 14 were rejected under 35 U.S.C 103 as being unpatentable over Koh and Yanez. Claims 3-4 and 7-10 were rejected under 35 U.S.C. 103 as being unpatentable over Koh and Yanez in further view of Gray-Owen and Blumberg. Applicant traverses that the instantly claimed methods were not easily conceivable from the prior art of Koh, Yanez, and Gray-Owen and Blumberg. Claim 1 has been amended to incorporate the limitations of claim 3. Claim 2 has been canceled rendering any traversal to the rejection of claim 2 moot.
Applicant traverses that there is no motivation to combine the prior art references as each teaches a different aspect of Applicant’s instant invention (See table on Pg 11 and Pg, 14) – Koh discloses CEACAM6-expressing stem cells, Yanez discloses use of ADSC-based therapeutics for graft versus host disease, and Gray-Owen and Blumberg disclose expression of CEACAM1 in T cells. Applicant further asserts that the Office’s combination of Koh, Yanez, and Gray-Owen and Blumberg is due to improper hindsight reasoning (Pg. 14).
Applicant’s traversal has been fully considered but is not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Koh is relied upon for the disclosure of ADSCs genetically engineered to overexpress a CEACAM family protein, CEACAM6, and that these cells exhibit increased viability (i.e., reduced apoptosis) which could enhance the proliferation ability and therapeutic effect of stem cells as stem cell therapies are limited by low survival after administration (Pg. 8, last para.). Koh discloses this effect as it relates to oxidative stress which is a hallmark of cell damage-related diseases and that stem cells are widely used as therapeutics in many diseases. Yanez discloses use of adipose-derived mesenchymal stem cells (Ad-MSCs) for the effective treatment of graft-versus-host disease and that repeated infusions, but not single doses, of Ad-MSCs were effective in treatment (Pg. 2589-2590, bridging para.). Thus, a skilled artisan would have been motivated, based on the disclosures of Koh and Yanez, to utilize ADSCs which overexpress a CEACAM family protein (i.e., CEACAM6) and have increased viability and resistance to oxidative stress for the treatment of graft versus host disease (a cell damage related disease) where Ad-MSCs are known to be effective with repeated doses. Based on the disclosure of Koh, a skilled artisan could have easily been directed to investigate other members of the CEACAM family of proteins and their potential for use in cell therapy (Pg. 8, last para.). Gray-Owen and Blumberg, in a review of CEACAM1 in cells in which CEACAM1 is naturally expressed, discloses that the CEACAM family of proteins is important in immunomodulation associated with inflammation (Abstract) and expression of CEACAM1 is associated with reduced cytokine production (Pg. 437, left col., 2nd para.), reduced T cell activation (Pg. 437, left col. 1st para.), and protection from targeted killing (Pg. 440, left col.). Therefore, a skilled artisan could have readily conceived genetically engineering stem cells to overexpress a different CEACAM protein, CEACAM1, based on the disclosure of Gray-Owen and Blumberg in order to protect stem cells after administration, which Koh discloses is a known limitation for stem cell therapy (Pg. 8, last para.) and to investigate the therapeutic effect in treating graft-versus-host disease.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant asserts on Pg. 11 that the stem cells genetically engineered to overexpress CEACAM1 are defined by their technical characteristics, specifically that they reduce degranulation and cytotoxicity of NK cells while also exhibiting increased in vivo survival rates which makes them applicable to treatment of various diseases. Applicant traverses that while CEACAM6 and CEACAM1 belong to the same family of proteins and share structural similarity of an extracellular Ig-like domain, this does not imply that they share similar effects or mechanisms of action (Pg. 11, last para.) and supplies Exhibit A as indicating that CEACAM1 and CEACAM6 are differentially expressed in the serum of pregnant vs. non pregnant individuals (Pg. 12). Applicant traverses that the function of any specific gene in one cell would not predict the outcome of expressing the gene in other cells (Pg. 14).
Applicant additionally asserts the effects of CEACAM1 could not be predicted by those of CEACAM6 as overexpression of CEACAM6 conferred protection against oxidative stress (as disclosed by Koh) and Applicant’s data indicates that overexpression of CEACAM1 induces immunomodulatory effects (Pg. 13). Applicant asserts that the teachings of Koh, Yanez, and Gray-Owen and Blumberg would not have led a skilled artisan to the instantly claimed method, nor would a skilled artisan have predicted the outcome of overexpression of CEACAM1 – specifically Applicant’s disclosure that CEACAM1 overexpression results in suppression of proliferation of T cells as well as cytokine secretion.
Applicant’s traversal has been fully considered but is not persuasive.
The motivation to combine the prior art of Koh, Yanez, and Gray-Owen and Blumberg is discussed above. With regard to Applicant’s traversal regarding reasonable expectation of success and the functional effects of the instant invention, although Applicant asserts that the functional effect of introduction of a gene in one type of cell does not predict the outcome of expression of the same gene in a different cell type, Koh discloses that CEACAM6 is known in other cell types to have anti-apoptotic and proliferative properties as well as confer resistance to oxidative stress (Pg. 6, last para.) and that ADSCs engineered to express CEACAM6 displayed similar properties (Pg. 8, 1st para.). Therefore, based on Koh, a skilled artisan would have had a reasonable expectation that stem cells engineered to express other CEACAM family proteins, such as CEACAM1, would also exhibit similar properties as cells in which CEACAM1 is naturally expressed. As acknowledged by Applicant. CEACAM1 and CEACAM6 are structurally very similar proteins with nearly 90% identity in their extracellular domains. Thus, the successful overexpression of CEACAM6 in cells to function as expected, provided a reasonable expectation of success that the overexpression of CEACAM1 in cells would function as expected.
Regarding Applicant’s assertion that various CEACAM proteins would have different effects or mechanisms of action and that Applicant’s finding that CEACAM1 suppresses T cell proliferation and cytokine secretion could not have been predicted by the prior art, Gray-Owen and Blumberg disclose that expression of certain CEACAM1 splice variants inhibits cytokine production (Pg. 437, left col., 2nd para. and Pg. 439, right col., 2nd para.) and T-cell proliferation and activation (Pg. 437, left col., 1st para. and right col., 2nd full para.; Pg. 439, right col., 2nd para.), and that CEACAM1 expression protects cells from targeted killing by NK cells (Pg. 440, left col.). Further, Yanez discloses immunomodulatory effects of administration of Ad-MSCs, specifically that administration of non-genetically engineered Ad-MSCs inhibits cytokine production (Pg. 2586, right col., 3rd para., Fig. 4) and suppress T cell proliferation (Pg. 2588, right col., last para.). Therefore, Applicant’s instant disclosure regarding the effects of CEACAM1 expression on T cell proliferation and cytokine secretion are what would be expected based on the teachings of the prior art.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
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