DETAILED ACTION
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 amendment and remarks, filed 12/23/25, are acknowledged.
Claims 1 and 12 have been amended.
Claims 24-25 have been added.
Claims 1-25 are pending and are under examination.
In view of Applicant’s claim amendments, the previous grounds of rejection are withdrawn and the following are new grounds of rejection. Applicant’s arguments relevant to the new grounds of rejection will be addressed below.
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.
Claim(s) 1-6, 10-18, and 22-25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2006/0034810.
The ‘810 publication teaches a method of treating a patient having a tumor (i.e. cancer) and in need of treatment comprising administering to the patient expanded and activated T cells (see paragraph 164 and 242, in particular). The ‘810 publication teaches that the T cells are activated by a process that comprises co-culturing the T cells with artificial K562 antigen presenting cells (i.e. human cells) that expresses MHC, CD86, CD64 and 4-1BBL (i.e. CD137L), and with cytokines including IL-15, IL-21 and IL-2 (See page 11, 13, 23, Table 2). The ‘810 publication teaches that the invention is suitable for use in human, horse, cat or dog subjects (See paragraph 176, in particular). The ’810 publication teaches administration by infusion (see paragraph 121, 182, and 185, in particular). The ‘810 publication teaches that the stimulated T cells upregulate perforin (see Fig. 4, in particular). Regarding the limitation that the cells have increased expression of granzyme B, it is noted that this is an inherent property of cytolytic T cells (see paragraphs 42 and 194, the T cells activated in the method of the ‘810 publication are cytolytic T cells with cytolytic activity). See, also paragraph 286 of the ‘810 publication where it is taught that performing and granzyme B staining is used as a gross measure to estimate cytolytic potential. Regarding the specific product by process describing how the activated immune cells are made, it is noted that the present claims recite a single method step, i.e. administering an effective amount of activated immune cells. Product by process limitations do not carry patentable weight in the absence of a structural or functional difference in the resulting product. In the instant case, the ‘810 publication teaches administering activated and expanded T immune cells, and therefore meets all the structural and functional limitations required in the present claims, even if they have been produced by a slightly different method.
Applicant’s arguments filed 12/23/25 have been fully considered, but they are not persuasive.
Applicant further argues that the activated immune cells used in the claimed treatment method are structurally and functionally distinct since the claimed expansion method induces granzyme B positive cells, and unlike other expansion methods also produces a large population of double negative T cells.
The present claims recite no limitations regarding double negative T cells. The claims require that the activated immune cells have increased perforin or granzyme B. As noted above, the ‘810 publication teaches that the resulting T cells have upregulated inflammatory cytokine and perforin (See Fig. 4). Furthermore, as noted above, the ‘810 publication explicitly teaches that the cells activated in the disclosed method have increased cytolytic activity, and also that increased perforin and granzyme B are a gross measure of cytolytic potential. In other words, increased expression of granzyme B is an inherent property of activated CTL with cytolytic properties. See also Fig. A of Applicant’s remarks filed on 12/23/25, where it is noted that expression of granzyme B is a measure of cytolytic function and mechanism of action of cytolytic immune cells, i.e. it is inherently linked to increased cytolytic function.
Claim(s) 1-8, 10-20, 22-25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by O’Connor, 2012 (of record).
O’Connor teaches a method of treating a patient having a tumor (i.e. a cancer) comprising administering activated T cells, wherein the T cells are activated by a
process that comprises co-culturing the T cells with artificial K562 antigen presenting
cells (i.e. human cells) that expresses CD86, CD64 and 4-1BBL (i.e. CD137L), IL-15,
and with cytokines IL-21 and IL-2 (See page 10, in particular)). O’Connor teaches the
patient is a canine companion animal (See entire document). O-Connor teaches
administration by infusion (see page 5, in particular). O’Connor teaches that the
patients have lymphoma (see page 5, in particular). O’Connor teaches that the T cells express increased granzyme B (see Fig. 6, in particular). Regarding the specific product by process describing how the activated immune cells are made, it is noted that the present claims recite a single method step, i.e. administering an effective amount of activated immune cells. Product by process limitations do not carry patentable weight in the absence of a structural or functional difference in the resulting product. In the instant case, the T cells of the prior art meet all the structural and functional limitations required in the present claims, even if they have been produced by a slightly different method
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.
Claims 1-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over O’Connor, 2012 (of record), in view of US 20120269860.
The teachings of O’Connor are described above.
O’Connor does not explicitly teach treating solid cancer such as melanoma.
The ‘860 publication teaches a method of treating a patient having a tumor (i.e. a cancer) comprising administering activated cytolytic T cells, wherein the T cells have been activated by a similar manner as O’Connor, by a process comprising co-culturing with APCs (which inherently would express CD64, CD86 and CD137L) and with IL-2, IL-15, and IL-21 (see page 1 and 5, in particular). The ‘860 publication teaches that the method can be used for treating a variety of tumors including leukemias or solid tumors such as melanoma (see page 3, in particular).
Therefore, it would be obvious to infuse the T cells produced in the method of O’Connor, in order to treat a hematological or solid cancer based on the teachings of the ‘860 publication, which teaches the suitability of cytolytic T cells for treating both leukemias or solid tumors like melanoma.
Claims 1-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Denman, 2012, in view of US 2006/0034810 and US 20130011376.
Denman teaches ex vivo expansion of NK cells (i.e. immune cells ), wherein the NK cells are expanded and activated in the presence of IL-2 and aAPC K562 cells that express membrane bound IL-15, IL-21, CD64, CD137L and CD86 (see abstract, page 3, and Table 1). Furthermore, said K562 cells also express HLA-Cw*3. (see page 10, in particular). Denman teaches that the NK cells exhibit high expression of perforin and granzyme B (see Fig. 5 and page 6, in particular).
Denman does not actually administer the NK cells, but does teach that the method has utility in propagating NK cells for use in adoptive immunotherapy (see abstract). Denman also teaches that NK cells are known to have an anti-cancer effect, particularly in sarcomas, neuroblastoma, melanoma, myeloma, lymphoma, and leukemia (see page 1 and Fig. 8, in particular).
The ‘810 publication teaches that activated immune cells propagated using K562 aAPCs are useful for administration to treating a patient having a tumor (i.e. cancer). The ’810 publication teaches administration by infusion (see paragraph 101, 121, 182, and 185, in particular). The ‘810 publication teaches treating human, horse, cat or dog subjects (see paragraph 176, in particular).
Likewise, the ‘376 publication teaches that NK cells can be administered to treat a variety of cancers including solid cancers and leukemia (see paragraph 143, in particular). The ‘376 publication teaches administration by infusion and treating human or animal subjects (see paragraph 208, 212, in particular).
Therefore, it would be obvious to infuse the NK cells produced in the method of Denman, to a patient, such as human, horse, cat or dog, in order to treat a hematological or solid cancer based on the teachings of the cited references.
Regarding the specific product by process describing how the activated immune cells are made, it is noted that the present claims recite a single method step, i.e. administering an effective amount of activated immune cells. Product by process limitations do not carry patentable weight in the absence of a structural or functional difference in the resulting product. In the instant case, the NK cells of Denman have been cultured with the exact same “proteins of interest” as recited in the instant claims, either in the culture medium or expressed from a K562 cells. This would result in NK cells which are structurally and functionally identical NK cells as compared to the product by process limitations of the present claims.
Applicant argues that the claims are not obvious for the same reasons set forth above.
The claims stand rejected for the reasons set forth above.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,040,094, in view of Denman, 2012. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘094 patent claims a method of treating a subject having cancer comprising: a) transfecting a cell expressing a major histocompatibility complex (MHC) molecule with a plurality of vectors each comprising a gene encoding a protein of interest and a glycosylphosphatidylinositol (GPI) signaling anchor, or a vector comprising a fusion gene encoding a plurality of proteins of interest and GPI signaling anchors, such that the proteins of interest are expressed and anchored to the cell surface via the GPI signaling anchors, wherein the proteins of interest include IL-15, IL-21, IL-2, CD86, CD64, and CD137L; b) lysing the cell of step (a) by hypotonic means to form a ghost cell (GHC) that is substantially free of all intracellular components; c) co-culturing the GHC with an immune cell isolated from the subject to expand and activate the immune cell, wherein the immune cell is a T cell or an NK cell; and d) infusing the activated immune cell into the subject. The ‘094 patent further claims said method comprising a step of transfecting a cell with a vector encoding a major histocompatibility complex (MHC) molecule and a glycosylphosphatidylinositol (GPI) signaling anchor. The ‘094 patent claims that the GPI anchored proteins are in a lipid raft, using HLA-Cw3, wherein the method is for treating a human, canine, or feline, wherein the cell is a K562, and wherein the cancer is a solid cancer such as melanoma or a leukemia. Regarding the increased expression of perforin or granzyme B, this with be an inherent property of the immune cells expanded in the ‘094 patent. Alternatively, it would also be obvious that the cells would have increased perforin and granzyme B based on the teachings of Denman, which teaches ex vivo expansion of NK cells with aAPC that express membrane bound IL-15, IL-21, CD64, CD137L and CD86 exhibit high expression of perforin and granzyme B (see Fig. 5 and page 6, in particular).
Claims 1-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-26 of copending Application No. 18/743,070 (reference application), in view of US 2006/0034810, in view of Denman, 2012. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘070 application claims a method of treating a subject having cancer comprising infusing an activated immune cell into the subject having cancer, wherein the activated immune cell is characterized and produced by a method comprising: a) transfecting a cell expressing a major histocompatibility complex (MHC) molecule with a plurality of vectors each comprising a gene encoding a protein of interest and a glycosylphosphatidylinositol (GPI) signaling anchor, or a vector comprising a fusion gene encoding a plurality of proteins of interest and GPI signaling anchors, such that the proteins of interest are expressed and anchored to the cell surface via the GPI signaling anchors, wherein the proteins of interest is selected from IL-15, IL-21, IL-2, CD86, CD64, and CD137L; b) lysing the cell of step (a) by hypotonic means to form a ghost cell (GHC) that is substantially free of all intracellular components; c) co-culturing the GHC with an immune cell isolated from the subject to expand and activate the immune cell, wherein the immune cell is a T cell or an NK cell; and d) infusing the activated immune cell into the subject. The ‘070 application further claims said method comprising a step of transfecting a cell with a vector encoding a major histocompatibility complex (MHC) molecule and a glycosylphosphatidylinositol (GPI) signaling anchor. The ‘070 application claims that the GPI anchored proteins are in a lipid raft, using HLA-Cw3, wherein the method is for treating a human, canine, or feline, wherein the cell is a K562, and wherein the cancer is a solid cancer such as melanoma or a leukemia. Although the ’070 application does not claim that the proteins of interest comprising all of IL-15, IL-21, IL-2, CD86, CD64 and CD137L, it would be obvious to select all of the recited proteins of interest since the ‘810 publication teaches that CD86, CD64 and 4-1BBL (i.e. CD137L), and cytokines including IL-15, IL-21 and IL-2 are useful in expanding immune effector cells for treating cancer. Regarding the increased expression of perforin or granzyme B, this with be an inherent property of the immune cells expanded in the copending application. Alternatively, it would also be obvious that the cells would have increased perforin and granzyme B based on the teachings of Denman, which teaches ex vivo expansion of NK cells with that express membrane bound IL-15, IL-21, CD64, CD137L and CD86 exhibit high expression of perforin and granzyme B (see Fig. 5 and page 6, in particular).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s statement that the rejections be held in abeyance is acknowledged.
No claim is 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644