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 .
Status of the Claims
Claims 89-103, 106-114, and 118-123 are pending.
Claims 89-92, 94-103, 106-108, and 111-114 are newly amended.
Claims 120-123 are newly added.
Claims 89-103, 106-114, and 118-123 have been examined on their merits.
Allowable Subject Matter
Claim 112 is allowed.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 89-103, 106-113, and 118-123 under 35 U.S.C. 103 as being unpatentable over Low et al. (WO2014100615A1, on IDS 12/18/2025, previously cited, hereafter “Low I”) in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) is withdrawn in order to address the claims as amended.
The rejection of claim 114 under 35 U.S.C. 103 as being unpatentable over Low et al. (WO2014100615A1, on IDS 12/18/2025, previously cited, hereafter “Low I”) in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”) is withdrawn in order to address the claims as amended.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 89-103, 106-111, 113-114, and 118-123 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 89 as amended recites “wherein the small molecule ligand is specific to a receptor overexpressed on a first type of cancer cell as compared to a baseline expression of the receptor on a healthy tissue or a different type of cancer cell.”
Independent claim 96 also recites this limitation.
At issue is specifically the limitation of relative expression of a small molecule ligand receptor in comparison to a different type of cancer cell.
It is noted that the claims do not require any specific small molecule ligand and do not require any specific cancer cell type.
Furthermore, the specification does not identify or test for relative expression levels in different cancer cells, but only generically states, “the first small molecule ligand is specific to a receptor overexpressed on a first type of cancer cell (as compared to a baseline expression of such receptor on a healthy tissue or a different type of cancer cell, collectively, a ‘non-targeted cell’)” (paragraph [0106]).
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Actual Reduction to Practice
In regards to claims 89-103, 106-111, 113-114, and 118-123, while as above, the specification generically identifies that “the first small molecule ligand is specific to a receptor overexpressed on a first type of cancer cell (as compared to a baseline expression of such receptor on a healthy tissue or a different type of cancer cell, collectively, a ‘non-targeted cell’)” (paragraph [0106]), the specification does not identify or test for relative expression levels of ligand receptors in different cancer cells.
Accordingly, Applicant has not demonstrated the full genus of relative levels of small molecule ligand receptors in various cancer cells.
State of the Art
In regards to claims 89-103, 106-111, 113-114, and 118-123, while as evidenced by Leone et al. (Oncotarget, 2015), it is known that a small molecule ligand receptors such as folate receptor may be overexpressed in breast cancer compared to non-cancerous tissue (Abstract, p30327; Introduction, p30327), this overexpression is not universal (“breast cancer patients, HFR (high affinity folate receptor) is overexpressed in 33% of primary tumors”, Introduction, p30327). Additionally, upregulation of folate can be different in different tissues (Fig. 1, p30328).
Therefore, as demonstrated by the art, even among the same types of cancer cells, a type of small molecule receptor ligand may or may not be upregulated.
Conclusion
In regards to claims 89-103, 106-111, 113-114, and 118-123, the claim requires broad limitation of wherein the small molecule ligand is specific to a receptor overexpressed on a first type of cancer cell as compared to a baseline expression of the receptor on a different type of cancer cell, and yet the instant specification provides no guidance nor description of the claimed relative expression levels of different small molecule receptors or cancer cells. Additionally, as above, as demonstrated in the art, whether a specific type of small molecule receptor is overexpressed can be different even within the same types of cancer.
Therefore, the Examiner concludes that there is insufficient written description of the instantly claimed limitation of wherein the small molecule ligand is specific to a receptor overexpressed on a first type of cancer cell as compared to a baseline expression of the receptor on a different type of cancer cell.
Specifically, there is no description of possible small molecule receptors or their relative expression levels as compared to possible cancer cells, the art explicitly teaches that expression levels may vary even within the same type of cancer cell, and a person of ordinary skill in the art would find that the specification inadequately described the claimed genus of cells.
Claims 90-95, 97-103, 106-111, 113-114, and 118-123 are rejected under 35 USC 112(a) for their dependence on claims 89 or 96.
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.
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 89-103, 106-113, and 118-123 are rejected under 35 U.S.C. 103 as being unpatentable over Low et al. (WO2014100615A1, on IDS 12/18/2025, previously cited, hereafter “Low I”) in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) as evidenced by Merriam-Webster (“rejuvenate” definition, retrieved from internet 07/14/2026) and Kogina et al. (Mol Cells, 2009).
In regards to claims 89, 91, and 99-100, Low I (who is noted is an instant inventor) teaches a method for treating cancers (such as breast cancer) in a subject (Claims 28-30, 48).
In regards to step (a), Low I teaches that the method comprises administering a “small molecule conjugate” (a compound) (claim 1). As taught by Low I, the adapter compound comprises a targeting moiety (a first moiety) and a conjugated a tumor receptor ligand (Claims 1, 13, and 28-30). In embodiments, Low I teaches that the tumor receptor ligand can be folate (claim 13), which is not only a well-known small molecule but it is also well-known that its receptor (folate receptors, e.g., FRα) can be overexpressed in cancer compared to at least healthy tissues.
Low I also teaches that the targeting moiety and the small molecule ligand are conjugated via a linker domain (first linker, claims 2, 4, and 40). Since the compound as taught by Low I is linked (bridged) it is an “adapter compound” (see paragraph [0009] of instant specification).
In regards to step (c) (it is noted that step (b) is discussed below), Low I teaches the method for treating cancer further comprises transfecting and administering a lymphocyte (T cell) population with a vector encoding a CAR (Claims 28-30). A person of ordinary skill in the art would have recognized that vectors encoding proteins such as a CAR would be operably linked to a promoter (indeed, Low I teaches specific embodiments of CAR promoters (paragraph [00108]). Low I teaches that the CAR has specificity to (i.e, is direct to) the (first) targeting moiety (claims 28-30).
In regards to step (b), in regards to the terms “activity-modifying compound” and “rejuvenating compound” it is noted that these terms are not specifically defined in the specification. Therefore, “activity-modifying compound” has broadly been interpreted as any molecule that can modify the activity of a cell.
In regards to “rejuvenating compound”, Merriam-Webster defines “rejuvenate” to mean “restore to an original or new state.” As a result, the term has been broadly interpreted to refer to any compound that has any cell restorative property (e.g., a drug).
It is noted that a rejuvenating compound can be a species of activity-modifying compounds.
For simplification, this molecule will hereafter be referred to as the “activity-modifying compound.”
Low I does not explicitly teach a step of administering the claimed activity-modifying compound.
However, Low II (who is the same inventor as Low I) teaches methods for rejuvenating cancer exhausted CAR T cells (Abstract; claims 1, 5-6, 18; Field of Invention, p1; Fig. 2, Fig. 9A).
Low II teaches that the method comprises administering to a subject a conjugate (a molecule) comprising a targeting ligand covalently linked to a payload drug which rejuvenates exhausted T cells (claims 1, 5-6, and 18). Thus, an activity-modifying compound linked to a second targeting moiety comprising a rejuvenating compound as claimed.
A person of ordinary skill in the art would have been motivated to modify the method of Low I and administer the activity-modifying compound as in claim 2 because Low II teaches that it is useful for rejuvenating cancer exhausted T cells which is highly desired for better treatment of solid tumors such as in breast cancer (Field of Invention, p1; Background, p1-2).
Furthermore, because Low I and Low II are the same inventor and because they are both in the same technical field of administering bipartite molecules to subjects and using T cells to treat cancers (such as breast cancer), it could have been done with predictable results and a reasonable expectation of success.
In regards to the wherein clauses, in embodiments, both Low I and Low II teaches that the targeting moiety can be FITC (Low I, claims 1, 5, 17; Low II, claims 2 and 21), which is the same molecule.
Additionally, Low I teaches that FITC binds to the CAR (the scFv region of an anti-FITC antibody) (claims 22, 34, 37; paragraph [0078]). As the second targeting moiety of Low II is also FITC it would also bind to this CAR.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
Thus, since the CAR T cells of Low I have these same receptors, when exposed to the activity-modifying compound of Low II it would result in the same property of binding, internalization, and subsequent effect on T cell activity in those cells.
In regards to claim 90, in specific embodiments, Low I teaches that the small molecule ligand can be a folate ligand or DUPA (Claims 1, 13, 39). It is well-known in the art that folate receptors and PSMA (the receptor for DUPA) are overexpressed in cancer cells and that folate and DUPA, respectively are specific for these receptors.
In regards to a first and second adaptor compound, Applicant should note that it is prima facie obvious to duplicate parts (see MPEP 2144.04(VI(B)). Indeed, because Low I teaches that the small molecule conjugate (adaptor compound) can be “FITC-folate [or] FITC DUPA” (claim 19), the disclosure of Low I suggests that the use of multiple adaptor compounds are within the scope of the invention.
In regards to claim 92, Low II teaches that the compound comprises FK506 (tacrolimus) (claim 2), which is a well-known immunosuppressive.
A person of ordinary skill in the art would have been motivated to select tacrolimus because Low II teaches tacrolimus (FK506) is useful for targeting T cells for rejuvenation (claims 1-2). Furthermore, because Low II teaches that CAR T cells can be rejuvenated by being contacted with compounds comprising tacrolimus as a targeting moiety (claims 18 and 21) and recommends their use in vivo (p1, Field of Invention; p18-19), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 93, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, 39).
In regards to claim 94, as above, Low I teaches that the first targeting moiety can ben FITC (claims 17, 19, 38).
In regards to claim 95, Low II teaches that the rejuvenating compound can be a TLR agonist (claims 8 and 10).
A person of ordinary skill in the art would have been motivated to select a TLR7 agonist because Low II teaches that TLR7 agonists are useful for rejuvenating T cells (claims 1-2). Furthermore, because Low II teaches that CAR T cells can be rejuvenated with TLR7 agonists (claims 8 and 24) and recommends their use in vivo (p1, Field of Invention; p18-19), it could have been done with predictable results and a reasonable expectation of success.
In regard to claims 96 and 98, it is noted that this is an independent claim. As above, Low I (who is noted is an instant inventor) teaches a method for treating cancers (such as breast cancer) in a subject (Claims 28-30, 48). Low I teaches that the subject can be administered a CAR (Claims 28-30, paragraph).
In regards to step (a), Low I teaches that the method comprises administering a “small molecule conjugate” (a compound) (claim 1). As taught by Low I, the adapter compound comprises a targeting moiety (a first moiety) and a conjugated a tumor receptor ligand (Claims 1, 13, and 28-30). In embodiments, Low I teaches that the tumor receptor ligand can be folate (claim 13), which is not only a well-known small molecule but it is also well-known that its receptor (folate receptors, e.g., FRα) can be overexpressed in cancer compared to at least healthy tissues.
Low I also teaches that the targeting moiety and the small molecule ligand are conjugated via a linker domain (first linker, claims 2, 4, and 40). Since the compound as taught by Low I is linked (bridged) it is an “adapter compound” (see paragraph [0009] of instant specification).
In regards to step (b), in regards to the terms “activity-modifying compound” and “rejuvenating compound” it is noted that these terms are not specifically defined in the specification. Therefore, “activity-modifying compound” has broadly been interpreted as any molecule that can modify the activity of a cell.
In regards to “rejuvenating compound”, Merriam-Webster defines “rejuvenate” to mean “restore to an original or new state.” As a result, the term has been broadly interpreted to refer to any compound that has any cell restorative property (e.g., a drug).
It is noted that a rejuvenating compound can be a species of activity-modifying compounds.
For simplification, this molecule will hereafter be referred to as the “activity-modifying compound.”
Low I does not explicitly teach a step of administering the claimed activity-modifying compound.
However, Low II (who is the same inventor as Low I) teaches methods for rejuvenating cancer exhausted CAR T cells (Abstract; claims 1, 5-6, 18; Field of Invention, p1; Fig. 2, Fig. 9A).
Low II teaches that the method comprises administering to a subject a conjugate (a molecule) comprising a targeting ligand covalently linked to a payload drug which rejuvenates exhausted T cells (claims 1, 5-6, and 18). Thus, an activity-modifying compound linked to a second targeting moiety comprising a rejuvenating compound as claimed.
A person of ordinary skill in the art would have been motivated to modify the method of Low I and administered the activity-modifying compound as in claim 2 because Low II teaches that it is useful for rejuvenating cancer exhausted T cells which is highly desired for better treatment of solid tumors such as in breast cancer (Field of Invention, p1; Background, p1-2).
Furthermore, because Low I and Low II are the same inventor, because they are both in the same technical field of administering bipartite molecules to subjects and using T cells to treat cancers (such as breast cancer), it could have been done with predictable results and a reasonable expectation of success.
In regards to the wherein clauses, in embodiments, both Low I and Low II teaches that the targeting moiety can be FITC (Low I, claims 1, 5, 17; Low II, claims 2 and 21), which is the same molecule.
Additionally, Low I teaches that FITC binds to the CAR (the scFv region of an anti-FITC antibody) (claims 22, 34, 37; paragraph [0078]). As the second targeting moiety of Low II is also FITC it would also bind to this CAR.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
Thus, since the CAR T cells of Low I have these same receptors, when exposed to the activity-modifying compound of Low II it would result in the same property of binding, internalization, and subsequent effect on T cell activity in those cells.
In regards to the timings, wherein the subject has been administered the CAR (thus before the compounds), according to MPEP 2144.04, selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). See also In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.).
In regards to claim 97, as above, Low II teaches that the rejuvenating compound can be a TLR agonist (claims 8 and 10).
A person of ordinary skill in the art would have been motivated to select a TLR agonist because Low II teaches that TLR agonists are useful for rejuvenating T cells (claims 1-2). Furthermore, because Low II teaches that CAR T cells can be rejuvenated with TLR agonists (claims 8 and 24) and recommends their use in vivo (p1, Field of Invention; p18-19), it could have been done with predictable results and a reasonable expectation of success.
In regards to claims 101-102, Low I teaches that the CAR has a scFV that binds to the targeted moiety (Claim 34). As the targeting moiety in both Low I and Low II can be FTIC (Low I, claim 17, etc. ; Low II claim 2, etc.), the scFV (or CAR) would be capable of binding to both first and second moieties. Low I teaches that the CAR can have an affinity of at least 100 pM (paragraph [0015]) (which is in a “sub-nanomolar” range), which is understood to refer to a high affinity in the art.
In regard to claim 103, Low I teaches that the scFV is an anti-FITC antibody (claims 8, 34).
In regards to claim 106, both Low I and Low II teach that linkers can be PEG linkers (claim 16; claim 12, respectively).
In regards to claim 107, Low I teaches that the linker can also be a polyproline (claim 16). As above, Low II teaches that the linker can be a PEG (claim 12). Thus, first and second linkers can be different.
In regards to claims 108 and 109, Low II teaches that the rejuvenating compound can comprise a TLR7 agonist with at least the first chemical structure as in claim 109 (claims 8 and 10).
A person of ordinary skill in the art would have been motivated to select a TLR7 agonist because Low II teaches that TLR7 agonists are useful for rejuvenating T cells (claims 1-2). Furthermore, because Low II teaches that CAR T cells can be rejuvenated with TLR7 agonists with the same formula (claim 8) and recommends their use in vivo (p1, Field of Invention; p18-19), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 110, as above, Low I teaches that the linker can also be a PEG (claim 16).
In regards to claim 111, as above, as above, Low I and Low II teach that linkers can be PEG linkers (claim 16; claim 12, respectively).
In regards to claim 113, Low II teaches that the compound can have an identical structure to the first structure in claim 113 (claim 11, fluorescein-TLR7).
A person of ordinary skill in the art would have been motivated to select a fluorescein-TLR7 because Low II teaches that fluorescein-TLR7 agonists are useful for rejuvenating T cells (claims 1-2 and 11). Furthermore, because Low II teaches that CAR T cells can be rejuvenated with fluorescein-TLR7 with the same structure (claim 11) and recommends their use in vivo (p1, Field of Invention; p18-19), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 118, Low I teaches that the cancer can be lung cancer (claim 48; paragraph [0051]).
In regards to claim 119, Low I teaches that the linker can be PEG and in particular PEG12 which has the same structure and overlaps with the claimed integer as in claim 120 (claims 16 and 43; paragraphs [0018, 0024, 0067]; for structure see Scheme 1, paragraph [00115]). Low II also teaches that the linker can be PEG including at least PEG6 which overlaps with the claimed integer (p28, last paragraph).
In regards to claim 120, Low I teaches that other linkers may be used including polyproline (paragraph [0018, 0024], 0067; claim 41).
As above, Low II Low II also teaches that the linker can be PEG including at least PEG6 which overlaps with the claimed integer (p28, last paragraph).
A person of ordinary skill in the art would have been motivated to use different linkers in order to account for differences in components of the compounds and provide different levels of stability and flexibility as taught by Low II (paragraph [0067]). Furthermore, because Low I teaches multiple linkers (such as polyproline) in addition to PEG, it could have been done with predictable results and a reasonable expectation of success.
In regards to claims Claim 121 and 122, as discussed above, Low II teaches that the compound comprises FK506 (tacrolimus) (claim 2), which as evidenced by Kogina, is a well-known immunosuppressive compound that inhibits the activation of T cells (Introduction, p125).
A person of ordinary skill in the art would have been motivated to select tacrolimus because Low II teaches tacrolimus (FK506) is useful regulating T cells as taught by Low II (Example 2, p21). Furthermore, because Low II teaches that tacrolimus (FK506) can be used to regulate T cells (Example 2, p21), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 123, as above, Low I teaches that the small molecule is folate (claim 13); Low I and Low II teach that the targeting moiety can be that the targeting moiety can be FITC (fluorescein isothiocynate) (Low I, claims 1, 5, 17; Low II, claims 2 and 21); and Low II teaches that the activity-modifying compound can be Toll-Like Receptor agonist (claims 8 and 10).
Therefore, the combined teachings of Low I and Low II renders the invention unpatentable as claimed.
Claim 114 is rejected under 35 U.S.C. 103 as being unpatentable over Low et al. (WO2014100615A1, on IDS 12/18/2025, previously cited, hereafter “Low I”) in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) as evidenced by Merriam-Webster (“rejuvenate” definition, retrieved from internet 07/14/2026) applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Low I, Low II, and Low III renders the invention unpatentable as claimed.
Double Patenting
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 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-14 of U.S. Patent No. 12,240,870 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-14 of U.S. Patent No. 12,240,870 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the patent are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-42 of U.S. Patent No. 11,779,602 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-42 of U.S. Patent No. 11,779,602 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the patent, are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,144,850 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,144,850 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the patent are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,269,862 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,269,862 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the patent are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 12,150,981 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 12,150,981 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the patent are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,759,480 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,759,480 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the patent are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 46-49, 51, 53, 57-58, 60-62, 64, 70-73, and 102 of copending Application No. 18/869,271 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 46-49, 51, 53, 57-58, 60-62, 64, 70-73, and 102 of copending Application No. 18/869,271 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the patent are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25, 31, 37-41 of copending Application No. 18/260,273 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25, 31, 37-41 of copending Application No. 18/260,273 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the Co-Pending Application are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 12-13, 16, 18-20, 22, 25-26, 30-33, and 39-43 of copending Application No. 18/255,094 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 12-13, 16, 18-20, 22, 25-26, 30-33, and 39-43 of copending Application No. 18/255,094 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the Co-Pending Application are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/963,158 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/963,158 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the Co-Pending Application are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a compound comprising a small molecule ligand linked to a targeting moiety, wherein the small molecule folate and the targeting moiety is a fluorescein-derivative and CAR T cells.
While the cited patent does not explicitly require a step of administering an activity modifying compound as in claim 89, as above, Low II teaches a system for rejuvenating CAR T cells comprising at least a conjugate (compound) comprising a targeting ligand (second moiety) linked by a linker domain (second linker) to a payload drug (a rejuvenating compound) with the different claimed embodiments (claims 1 and 5-6; Fig. 2, Fig. 9A).
A person of ordinary skill in the art would have been motivated to administer an activity modifying compound as in step (b), in order to rejuvenate and deliver payloads to antigen exhausted CAR T cells, as taught by Low II (p1, Field of Invention; p18-19).
In regards to the remaining embodiments, while the cited patent does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments because Low I teaches that they are useful for treating cancer (claims 28 and 29). Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 89-103, 106-111, 113, and 118-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8 of copending Application No. 18/687,785 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”).
Claim 114 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8 of copending Application No. 18/687,785 in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) and Low et al. (WO2014100615A1, on IDS 12/18/2025, hereafter “Low I”) as applied to claim 89 above, and further in view of Low et al. (US20160166679A1, 2016, hereafter “Low III”).
While the instant claims and the claims of the Co-Pending Application are not identical, they are not patentably distinct because the claims of both inventions are drawn to a method for treating cancer comprising administering a first compound comprising a small molecule ligand linked to a targeting moiety; a compound comprising a TLR agonist linked to a second targeting moiety, and administering CAR T cells.
In regards to the specific embodiments, while the cited co-pending application does not specifically claim the specific embodiments as in these claims, these are all embodiments taught by Low I or Low II corresponding to the first and second compounds (as discussed in depth above). A person of ordinary skill in the art would have been motivated to incorporate these embodiments for the first compound because Low I teaches that they are useful for treating cancer (claims 28 and 29). A person of ordinary skill in the art would have been motivated to incorporate the second compound because Low II teaches that they are use for rejuvenating T cells (claims 1 and 5-6; Fig. 2, Fig. 9A; p1, Field of Invention; p18-19).
Furthermore, because Low I is drawn to a method that comprises administering a small molecule conjugate (a compound) comprising a targeting moiety (a first moiety) conjugated to a tumor receptor ligand (i.e., a small molecule; e.g., folate, a well-known small molecule) (Claims 1, 13, and 28-30) with a linker domain (claims 2, 4, and 40), it could have been done with predictable results and a reasonable expectation of success. Additionally, because Low II teaches that these compounds can be used to rejuvenate cells (claim 18) and teaches that the system can be used to deliver payloads to cancer antigen exhausted CAR T cells in vivo (p1, Field of Invention; p18-19), it could have been done with predictable results and a reasonable expectation of success.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
In regards to claim 114, in regards to small molecule ligand structure of an adaptor compound comprising a structure having the generic formula as in claim 114, it is noted that this is a folate variant.
While, as above, Low I teaches that the small molecule ligand can be folate (Claims 1, 13, and 28-30) and teaches folate structures (paragraphs [0073-0074]), the folate structures as taught by Low I, while similar, does not appear the be the same structure as in claim 114 (specially, group corresponding to X1 in Low I is a carbonyl (C=O), which is not a group as identified in claim 114 as corresponding to X1).
However, folate variants with the structure as in claim 114, were known before the effective filing date.
For example, Low III (again, who is both the same inventor as Low I and is a named instant inventor) teaches a folate which overlaps in structure with the structure as in claim 114 (claim 7).
In particular, in the left-most bicyclic structure of Low III (claim 7), T1 can be —N═C(X)— which results in a structure that is identical to N=C(X1) as in claim 114 (both the X in Low III and X1 in instant claim 114 can be hydrogen). The remaining structural elements are likewise the same or overlap.
A person of ordinary skill in the art would have been motivated to use folate with this generic structure because Low III teaches that this molecule is suitable for treating a wide range of cancers (claims 3 and 4). Furthermore, because Low I and III both teach treating cancer patients with folates linked to targeting molecules (claim 1 of Low III) and because Low III teaches that folate compounds can have the same generic structure as in claim 114, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant argues that the present methods relate to T cell therapy wherein, through a single CAR, the adapter compound can target the T cell to the tumor and can internalize the activity-modifying compound (Remarks, p28-34).
Specifically, Applicant argues that as amended, step (c) of claim 89 requires, inter alia, that “the first targeting moiety and the second targeting moiety have the same structure and are recognized and bound by the CAR, and binding the recognition region of the CAR to the second targeting moiety internalizes the activity modifying compound, or the pharmaceutically acceptable salt thereof” (Remarks, p28-30).
Applicant argues that this feature is both not taught by the prior art that there was no motivation to arrive at the present claims with any reasonable expectation of success (Remarks, p28-34).
In regards to Low I, Applicant argues that Low I discloses a CAR system for use in the treatment of cancer comprising a small conjugate molecule and a CAR-T cell, where the small conjugate molecule comprises a targeted moiety conjugated to a tumor receptor ligand (Remarks, p31).
However, Applicant argues that the CAR system of Low I allows for focused targeting of cancer cells by the CAR-T cell via a bridging molecule (i.e., small conjugate molecule), but that Low I not contemplate intracellular delivery of any molecule upon binding of the molecule to the CAR (Remarks, p31).
Applicant’s arguments filed 06/24/2026 have been fully considered but are not found persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As discussed above, Low I does not explicitly teach a step of administering the claimed activity-modifying compound, Low II (who is the same inventor as Low I) teaches methods for rejuvenating cancer exhausted CAR T cells (Abstract; claims 1, 5-6, 18; Field of Invention, p1; Fig. 2, Fig. 9A).
Low II teaches that the method comprises administering to a subject a conjugate (a molecule) comprising a targeting ligand covalently linked to a payload drug which rejuvenates exhausted T cells (claims 1, 5-6, and 18). Thus, an activity-modifying compound linked to a second targeting moiety comprising a rejuvenating compound as claimed.
As discussed above, a person of ordinary skill in the art would have been motivated to modify the method of Low I and administer the activity-modifying compound as in claim 2 because Low II teaches that it is useful for rejuvenating cancer exhausted T cells which is highly desired for better treatment of solid tumors such as in breast cancer (Field of Invention, p1; Background, p1-2).
Furthermore, because Low I and Low II are the same inventor and because they are both in the same technical field of administering bipartite molecules to subjects and using T cells to treat cancers (such as breast cancer), it could have been done with predictable results and a reasonable expectation of success.
In regards to the wherein clauses (i.e., the properties of the first and second targeting moieties, their binding to a CAR and subsequent internalization and effect on T cells), as discussed above, in embodiments, both Low I and Low II teache that the targeting moiety can be FITC (Low I, claims 1, 5, 17; Low II, claims 2 and 21), which is the same molecule.
Additionally, Low I teaches that FITC binds to the CAR (the scFv region of an anti-FITC antibody) (claims 22, 34, 37; paragraph [0078]). As the second targeting moiety of Low II is also FITC it would also bind to this CAR.
In regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
Thus, since the CAR T cells of Low I have these same receptors, when exposed to the activity-modifying compound of Low II it would result in the same property of binding, internalization, and subsequent effect on T cell activity in those cells.
Applicant argues that Low II does not cure these deficiencies (Remarks, p31).
Specifically, Applicant argues that Low II discloses a system for rejuvenating exhausted CAR T cells that expressly relies upon two distinct receptors: (1) the classical CAR construct, which targets tumor antigens; and (2) a separate fusion receptor, specifically, an anti- FITC scFv or FKBP domain linked to a folate receptor for binding and internalizing the payload drug conjugate. See, e.g., Low II, Abstract; Summary of the Invention; Fig. 2 (Remarks, p31).
Applicant argues that this separate, dedicated receptor for payload delivery is a central design feature of the Low II system, and that there is no teaching or suggestion in Low II that the classical CAR itself could or should serve as the receptor for internalizing the activity-modifying compound (Remarks, p31-33).
Applicant argues that there is no articulated and sufficient reason why a POSITA would have been motivated to redesign the Low II system which relies on a separate fusion receptor for payload delivery (Remarks, p31).
Applicant argues that upon reading Low II, a POSITA would have understood that the separate fusion receptor design was not merely one option among many but was used to exploit the constitutive internalization properties of the folate receptor (Remarks, p32-33). Continuing, Applicant argues that there is no suggestion that the CAR’s recognition region could substitute for the fusion receptor’s internalization function (Remarks, p32-33).
Therefore, Applicant concludes that there was no reasonable expectation of success in arrived at the claimed invention un view of the combination of cited references (Remarks, p33).
Applicant’s arguments filed 06/24/2026 have been fully considered but are not found persuasive.
In regards to the classical CAR constructs and fusion receptor proteins of Low II, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
As discussed above, a person of ordinary skill in the art would have been motivated to modify the method of Low I and administer the activity-modifying compound of Low II because Low II teaches that it is useful for rejuvenating cancer exhausted T cells which is highly desired for better treatment of solid tumors such as in breast cancer (Field of Invention, p1; Background, p1-2).
Furthermore, because Low I and Low II are the same inventor and because they are both in the same technical field of administering bipartite molecules to subjects and using T cells to treat cancers (such as breast cancer), it could have been done with predictable results and a reasonable expectation of success.
Continuing in regards to Low II, Applicant argues that POSITA may have expected that modifying a CAR to promote endocytosis would impair its primary cytotoxic function (Remarks, p33).
Applicant’s arguments filed 06/24/2026 have been fully considered but are not found persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. modifying a CAR to promote endocytosis) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Instead, the claims only suggest that endocytosis is a property of the CAR upon contact with the targeting moieties.
However, as discussed above, in regards to the properties of binding the second targeting moiety to the CAR, Low II teaches that the effect of binding is internalization which allows the drug (the rejuvenating compound to execute its regulatory function on the exhausted T cell (i.e., rejuvenate it, or modifies the activity of the T cell) (Abstract; p16 last paragraph; Example 2, p21; claims 18 and 21).
Thus, since the CAR T cells of Low I have these same receptors, when exposed to the activity-modifying compound of Low II it would result in the same property of binding, internalization, and subsequent effect on T cell activity in those cells.
Applicant argues that there are unexpected results citing the results of examples 14-20 and Figs. 2-4) (Remarks, p35-36).
Applicant’s arguments filed 06/24/2026 have been fully considered but are not found persuasive.
In regards to Applicant’s allegations of unexpected results, whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (see MPEP 716.02(d)).
In the instant case, the claims do not require any specific result.
Applicant argues that claim 114 is not obvious because it depends on claim 89 which is not obvious (Remarks, p37).
Applicant’s arguments filed 06/24/2026 have been fully considered but are not found persuasive because claim 89 is prima facie obvious as discussed above.
In regards to the double-patenting rejections, Applicant argues that Low I, Low II, and Low III deficient and therefore, requests withdrawal of the rejections (Remarks, p37-48).
Applicant’s arguments filed 06/24/2026 have been fully considered but are not found persuasive. Specifically, Low I, Low II, and Low III are not deficient (the teachings of Low I and Low II are discussed above, Applicant does not make specific arguments in regards to Low III).
Applicant requests abeyance Co-Pending Applications rejected under non-statutory double-patenting (Remarks, p43-48).
Applicant’s request filed 06/24/2026 is noted. However, because the base claims are still prima facie obvious and Applicant has not that a terminal disclaimer the rejections of record stand.
Conclusion
Claim 112 is allowed.
Claims 89-103,106-111,113-114 and 118-123 are rejected as discussed above.
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.
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