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
1. Claims 1-19 are the original claims filed 11/28/2022. In the Reply of 3/5/2026, no claims are amended, canceled or added. Claims 1-19 are all the claims.
Election/Restrictions
2. Applicant’s election without traverse of Group I in the reply filed on 3/5/2026 is acknowledged.
3. Claim 17 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/5/2026.
4. Claims 1-16 and 18-19 are the claims under examination.
Priority
5. USAN 17/994,787, filed 11/28/2022, is a Continuation in Part of 15/739,596, filed 12/22/2017, now U.S. Patent # 11655452, and having 2 RCE-type filing therein,
15/739,596 is a National Stage entry of PCT/US2016/039306, International Filing Date: 06/24/2016, PCT/US2016/039306 Claims Priority from Provisional Application 62/184,321, filed 06/25/2015, PCT/US2016/039306 Claims Priority from Provisional Application 62/235,840, filed 10/01/2015, PCT/US2016/039306 Claims Priority from Provisional Application 62/244,435, filed 10/21/2015.
USAN 18520936, filed on 11/28/2023, abandoned, is a Continuation in Part of 17/994,787, filed on 11/28/2022.
The priority filing date of 06/24/2016 for PCT/US2016/039306 is granted for the instant method claims drawn to the cCAR for treating autoimmune diseases using cCAR binding to the instant claimed target antigens with the exception of the species GPRC5D.
The priority filing date of 11/28/2022 for is granted for the species of cell surface antigen GPRC5D.
Information Disclosure Statement
6. AS of 4/22/2026, a total of three (3) IDS are filed: 1/25/2023; 1/9/2025; and 1/9/2025. The corresponding initialed and dated 1449 form is considered and of record.
Objections
Specification
7. The disclosure is objected to because of the following informalities:
a) The figure legends to Figures 66 and 78 are objected to for failing to include sequence identifiers for the nucleotides > 10 nucleic acids in length and the amino acid sequence > 4 amino acids in length, respectively, that are shown in the corresponding figure. See 37 CFR 1.821-1.825. Note, the figure legend for Figure 78 is objected to for “GGGS”.
b) The use of the term NCBI, BiTE, NSG, EVOS, Lipofectamine, IVIS, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
c) The specification fails to include sequence identifiers for the nucleotides > 10 nucleic acids in length pursuant to 37 CFR 1.821-1.825:
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d) The specification fails to include sequence identifiers for the amino acid sequences > 4 amino acids in length pursuant to 37 CFR 1.821-1.825:
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e) Amend the specification to correct the symbol error at
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.
f) The specification recites the term “CDS” that has no known meaning.
g) Amend the specification to replace: “CTAL-4” with “CTLA-4”; and “TGFR beta” with “TGF beta R.”
Appropriate correction is required.
Claim Objections
8. Claims 1-16 and 18-19 are objected to because of the following informalities:
a) Claims 1-16 and 18-19 recite the term “CDS” in claim 1 that has no known meaning. The specification teaches an antigen is CD5 at if what is intended is CD5:
[0015] In another embodiment, the present disclosure provides a method of reducing the number of target cells including the steps of (i.) contacting said target cells with an effective amount of an engineered cell having at least one chimeric antigen receptor polypeptide, for engineered cells having multiple chimeric antigen receptor polypeptides, each chimeric antigen receptor polypeptides are independent; and (ii.) optionally, assaying for the reduction in the number of said cells. The target cells include at least one cell surface antigen selected from the group consisting of interleukin 6 receptor, NY-ESO-1, alpha fetoprotein (AFP), glypican-3 (GPC3), BAFF-R, BCMA, TACI, LeY, CD5, CD13, CD14, CD15 CD19, CD20, CD22, CD33, CD41, CD45, CD61, CD64, CD68, CD117, CD123, CD138, CD267, CD269, CD38, Flt3 receptor, and CS1.
b) Amend Claims 1-16 and 18-19 for clarification in claim 1 to set forth that the dual CAR comprises two CAR units as supported in the specification at
[0259] … the dual CAR where the one CAR unit targets for T-cells by selecting at least one of the target antigens from the following group: CD2, CD3, CD4, CD5, and CD7; and the other CAR unit targets for B-cells by selecting at least one of the target antigens from the following group: CD19, CD20, CD22; or plasma cells by selecting at least one of the target antigens from the following group or target antigen BCMA, CD38, CS1 (CD319. SLAMF7) and CD138.
For example, amend claim 1 to recite
A method for treating an autoimmune disorder, the method comprising administering to a patient in need thereof, a dual CAR, wherein the dual CAR comprises a) a CAR unit for targeting a T-cell surface-expressed antigen, wherein the antigen is CD2, CD3, CD4, CD5, or CD7, and
b) a CAR unit for targeting a B-cell surface-expressed antigen, wherein the antigen is CD19, CD20 or CD22, or a plasma-cell surface-expressed antigen, wherein the antigen is BCMA, CD38, CS1, CD138, or GPRC5D
c) Amend claim 1 to recite “to a patient in need thereof,”.
d) Amend claim 8 to recite “wherein the method further comprises administering a steroid, [or] a B-cell inhibitory treatment, [or] a plasma cell inhibitory treatment, or an immunosuppression treatment.”
e) Amend claim 9 to replace “(AV V)” with “(AVV).”
f) Amend claim 9 to:
i) delete duplicate citation of the species “myasthenia gravis” and “Pemphigus vulgaris.”
ii) insert a comma between “Bullous pemphigoid” and “Grave’s disease.”
iii) capitalize “myasthenia gravis”, “systemic lupus erythematosus”, “membrane neuropathy”, and “rheumatoid arthritis” for consistency with the other species of the claim.
g) Amend claim 11 to replace “au to immune” with “autoimmune.”
h) Amend claim 18 to replace: “CTAL-4” with “CTLA-4”; and “TGFR beta” with “TGF beta R.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
9. Claims 4, 9 and 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
a) Claim 4 recites the limitation "another CAR unit". There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not support the phrase “CAR unit” much less providing the antecedent basis for “another” in claim 4.
b) Claim 4 to recite “wherein administration to the patient in need thereof results in depletion of T- cells expressing CD7 surface antigen, or B-cells or plasma cell populations or a combination thereof.” It is not clear how the deletion of B-cells or plasma cells occurs using a dual CAR comprising a CD7CAR. There is no correlation between the “another CAR unit” to the dual CAR much less to the depletion of B-cells or plasma cell populations or combinations thereof.
c) Claim 4 recites the limitation "plasma cell populations". There is insufficient antecedent basis for this limitation in the claim. Claim 1 makes no reference to a population of plasma cells or plasma cell populations.
d) A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation “rheumatoid arthritis”, and the claim also recites “anti-PAD4-activating rheumatoid arthritis”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
e) Claim 12 concludes with a period after the phrase “Type 1” and further concludes with a period after the term “Diabetes.” The POSA cannot reasonably ascertain the intended metes and bounds for the claimed subject matter.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
10. Claims 5-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 5-7 each recite “wherein the dual CAR binds to cells expressing___”. Claim 1 is drawn to T-cells, B-cells or plasma cells, therefore claims 5-7 are broadening in scope for the generic cell type.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Written Description
11. Claims 18-19 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.
The claims under rejection are directed to a method for treating an autoimmune disorder in a patient in need thereof, wherein the dual CAR comprises an enhancer selected from IL- 15/IL-15sushi, IL-15/IL-15sushi anchor, PD-1, PD-LI, CSFIR, CTAL-4, TIM-3, TGFR beta, IL-2, IL-7, IL-12, IL-15, CCL-19, CCL-21, IL-15RA, IL-21, functional fragments thereof [of the enhancers], or combinations thereof.
Thus, to satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed group – or genus – of fragments, it must be clear that: (1) the identifying characteristics of the claimed fragments have been disclosed, e.g., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics; or (2) a representative number of species within the genus must be disclosed. See MPEP § 2163, Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed. Cir. 1994).
In giving the term ‘fragment [of an enhancer]’ its broadest reasonable interpretation, the number and types of proteins which can be considered a fragment of an enhancer is extraordinarily great, and can be interpreted to even include a single amino acid. Applicant’s disclosure does not provide any exemplary fragments, instead teaching different examples of the full-length enhancers. Therefore, there is minimal disclosure of acceptable fragments of enhancers.
Regarding disclosure of identifying characteristics of the claimed fragments, a review of the Specification fails to provide a definition of the structural characteristics the fragments encompassed by the current claims must have in regards to the enhancer. As such, Applicant has not identified any particular core chemical structure or function (along with a correlation between function and a specific conserved structure) of the enhancer which must be shared by all fragments thereof; thus, one of ordinary skill in the art would not immediately envisage all fragments of the enhancer, as currently claimed. Therefore, Applicant has not disclosed the identifying characteristics of the claimed fragments.
Regarding disclosure of a representative number of species within the genus, a review of the Specification shows that Applicants have not disclosed any acceptable fragments of the enhancer. This lack of disclosure evidently does not constitute a representative number for such a broad genus as is encompassed by the breadth of ‘fragments of an enhancer’. Therefore, Applicant has not disclosed a representative number of species, as would be required to support description and to show possession of the entire genus.
Thus, one of ordinary skill in the art, in looking to the instant Specification, would not be able to determine that Applicant was in possession of the invention, as claimed, at the time the invention was made. Accordingly, the claim is considered to lack sufficient written description and are properly rejected under 35 USC 112(a).
Written Description/ New Matter
12. Claims 1-16 and 18-19 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.
Claim interpretation
The claims are drawn to the generic method for treating an autoimmune disorder, the method comprising administering to a patient in need thereof a dual CAR, wherein the dual CAR binds to an antigen expressed on T-cells and an antigen on the surface of B-cells or plasma cells, wherein the antigen expressed on T cells is CD2, CD3, CD4, CDS, or CD7, and wherein the antigen on the surface of B cells or plasma cells is CD 19, CD20, CD22, BCMA, CD38, CD138, CSI, or GPRC5D.
None of the claims identify the engineered structural design of the dual CAR much less with its being transfected into a T- or NK-cell. See parent USPN 11655452 for claims drawn to the dual CAR-T cell:
1. An ex vivo engineered T cell or NK cell co-expressing two distinct chimeric antigen receptor (CAR) units at the cell surface, wherein the engineered T cell or NK cell comprises a nucleotide sequence comprising from 5′ to 3′ a single promoter selected from human elongation factor-1 alpha (EF-1α) or spleen focus forming virus (SFFV), a first polynucleotide encoding a first chimeric antigen receptor polypeptide (CAR), a nucleotide encoding a viral self-cleavage peptide, a second polynucleotide encoding a second chimeric antigen receptor polypeptide (CAR), and an enhancer selected from the group consisting of secreted IL-15/IL-15sushi, Il-15/Il-15 sushi anchor, PD-1, PD-L1, CSF1R, CTLA-4, TIM-3, TGFR-beta, IL-2, Il-7, IL-12, IL-15, IL-15RA, IL-21 or a functional fragment thereof, or a combination thereof, wherein said enhancer is separated from the first CAR and second CAR by a second cleavage site that flanks either end of the two distinct CAR units, wherein: the first CAR comprises a first signal peptide, a first antibody binding domain, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and the second CAR comprises a second signal peptide, a second antibody binding domain, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; and wherein the first antibody binding domain and the second antibody binding domain are different and each bind to a different target, wherein the targets of the first and second antibody binding domains irrespective of order are CD19 and CD20, or CD123 and CD33, or B cell maturation antigen (BCMA) (CD269) and CD19, or BCMA (CD269) and CD38, or and BCMA (CD269) and CS1, wherein the first and second co-stimulatory domains are intracellular, and wherein the cleavage site is selected from the group consisting of porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), equine rhinitis A virus (ERAV) 2A (E2A), and FMDV 2A (F2A).
2. The engineered T cell or NK cell according to claim 1, wherein the target of the first antibody binding domain comprises CD123, the target of the second antibody binding domain comprises CD33, the first co-stimulatory domain comprises CD28, the second co-stimulatory domain comprises 4-1BB, the cleavage site comprises P2A, and the engineered cell is a T cell.
3. The engineered T cell or NK cell according to claim 1, wherein the first co-stimulatory domain and the second co-stimulatory domain are different.
4. The engineered T cell or NK cell according to claim 1, wherein the first co-stimulatory domain comprises CD28, and the second co-stimulatory domain comprises 4-1BB.
None of the claims explicitly nor implicitly recite a transfected, engineered cell comprising the dual CAR that is administered to the subject of the method invention.
The specification does not support the use of just any naked dual CAR that is administered to the subject of the method invention. MPEP 706.03(m) states in part "New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to §608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.”).
Enablement
13. Claims 1-16 and 18-19 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Claim interpretation
The claims are drawn to the generic method for treating an autoimmune disorder, the method comprising administering to a patient in need thereof a dual CAR, wherein the dual CAR binds to an antigen expressed on T-cells and an antigen on the surface of B-cells or plasma cells, wherein the antigen expressed on T cells is CD2, CD3, CD4, CDS, or CD7, and wherein the antigen on the surface of B cells or plasma cells is CD 19, CD20, CD22, BCMA, CD38, CD138, CSI, or GPRC5D.
“in need thereof”: the specification implies the use of the invention in the prevention of the disease in a subject at risk at
[0343] A patient in need thereof includes patients suffering from a disease that would benefit from the claimed methods of treatment or a patient at risk for developing a disease that would benefit from the claimed methods of treatment includes subject.
[0346] The disclosure is a novel approach to reset the immune system. In a further embodiment the disclosure resets the immune system via a CAR. therapy, whereby this approach treats patients with a high risk for developing an autoimmune disorder and subsequent organ damage which may manifest to be substantial.
None of the claims identify an engineered structural design of the dual CAR much less with its being transfected into a T- or NK-cell in order to treat and/or prevent an autoimmune disorder.
Disclosure in the Specification
The specification teaches an example of a cCAR construct intended for targeting autoreactive T cells at
[0106] FIG. 80. A schematic representation of cCAR construct (CD7-CD19 cCAR). The construct comprises a single promoter driving the expression of two modular units of CARs linked by a P2A peptide. Upon cleavage of the linker, the cCARs split and engage upon targets expressing CD7 and/or CD19. As a novel cCAR construct, the co-stimulatory domains of the construct may include, but is not limited to, 4-1BB on the CD7 CAR segment and a CD28 region on the CD19 CAR. Co-stimulatory domain in each CAR can be the same or different. Each CAR consists of a scFv, CD8 hinge (H) and transmembrane (TM) regions, and a co-activator fused to the CD3zeta signaling domain. The hinge region of CD7CAR also contains two CD20 RTX-binding epitopes. The CD7-CD19 cCAR is designed to target autoreactive T cells expressing CD7 and autoreactive B cells expressing CD19.
The specification teaches treatment of autoimmune disorders achieves depletion auto-T-cells, B-cells, plasma cells and repopulation lymphocyte counts at
[0295] Therefore, existing treatments for autoimmune disorders are not always effective in the induction or maintenance of remission and/or may have undesirable side effects. Thus, reasserting the clear and present need for further therapies for the treatment and management of autoimmune disorders. The novel invention is to reset the immune system by depleting disease causing auto- T-cells, B-cells, plasma cells and re-population lymphocyte counts from bone marrow stem cells. One can create the compound chimeric antigen receptor dual CARs where one chimeric antigen receptor (CAR) unit targets for T-cells by selecting one of the target antigens from the following group: CD2, CD3, CD4, CD5, and CD7; and the other CAR unit targets for B-cells by selecting one of the target antigens from the following group: target antigen CD19, CD20, CD22; or plasma cells by selecting one of the target antigens from the following group or target antigen BCMA, CD38, CS1, and CD138.
The specification does not provide a single, in vitro or in vivo, cell-based assay to demonstrate a therapeutic or prophylactic effect of any cCAR (dual CAR) as a correlate to an autoimmune disease.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19, 24 (CCPA 1970). "[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.'" Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability” (citing In re Marzocchi, 439 F.2d 220, 223-24, 169 USPQ 367, 369-70 (CCPA 1971)).
“In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work.”
Prior Art on Antibody Expression and Stability
Hunter et al (Current Protocols in Protein Science 95, e77 . doi: 10.1002/cpps.77) teach that numerous variables are involved in mammalian protein expression are interdependent, so changing one can have unexpected downstream effects. No choice in the development of a mammalian expression system is made in isolation, as they tend to have both upstream and downstream effects (Fig. 1).
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Frenzel et al. (Frontiers Immmunol. 4:1-20 (published: 29 July 2013)) teach numerous examples of mammalian cell systems for expressing antibodies (see Table 1 under transient and stable transfections), but “In principle, there is no “universal” production system which can guarantee high yields of recombinant antibody, particularly as every antibody-based molecule itself will cause its own issues in terms of expression.”
Therefore, due to the unpredictability of immunotherapeutics in general and in view of the insufficient guidance and/or working examples concerning the use of the claimed cCAR (dual CAR) much less cCAR-T cells as immunotherapeutic agents, in vitro and in vivo, in combination with the second agents, one skilled in the art would reasonably conclude that the broadly claimed invention was not fully supported in the specification, and thereby removing applicants from full possession of the invention and the POSA to make and use the method absent unduly burdensome trial and error experimentation.
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.
14. Claims 1-16 and 18-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 18/520,972 (reference application US 20240350632). The reference application is not afforded safe harbor under 35 USC 121 because the reference claims share no continuity nor a restriction/speciation with the claims of the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are overlapping for a method of treating an autoimmune disorder in a subject comprising administering a dual CAR or compound CAR or tandem CAR, that binds to an antigen expressed on T-cells or NK cells selected from the group consisting of CD2, CD3, CD4, CD5, and CD7, and that binds to an antigen expressed on B-cells or plasma cells selected from the group consisting ofCD19, CD20, CD22, BCMA, CD38, CD138, CSI, and GPRC5D.
Ref claims are inclusive of the cCAR construct and methods of treatment:
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
15. Claims 1-16 and 18-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-5 of U.S. Patent No. US 11,820,819 B2. The reference patent is not afforded safe harbor under 35 USC 121 because the reference claims do not share continuity nor a restriction/speciation with the claims of the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claim renders obvious the instant claims. More specifically, the patented claim is not identical because no single patent claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patent claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 4 is directed to a method for depleting antibody producing B cells and/or plasma cells in a patient with an autoimmune condition, said method comprising:
administering to said patient in need thereof a composition comprising an engineered T cell or NK cell co-expressing two distinct chimeric antigen receptor (CAR) units at the cell surface, wherein the engineered T cell or NK cell comprises a nucleotide sequence comprising from 5′ to 3′ a promoter selected from human elongation factor-1 alpha (EF-1α) or spleen focus forming virus (SFFV), a first polynucleotide encoding a first chimeric antigen receptor polypeptide (CAR), a nucleotide encoding a first, self-cleavage peptide, a second polynucleotide encoding a second chimeric antigen receptor polypeptide (CAR) a nucleotide encoding a second self-cleavage peptide, and a third polynucleotide encoding a fusion protein consisting of IL-15 linked to a soluble domain of IL-15Rα (sushi) and secreted as a soluble IL-15/IL-15 sushi complex wherein:
(i) the first CAR comprises a first signal peptide, a first antibody binding domain, a first hinge region, a first transmembrane domain, a first CD28 or 4-1BB co-stimulatory domain, and a first signaling domain; and
(ii) the second CAR comprises a second signal peptide, a second antibody binding domain, a second hinge region, a second transmembrane domain, a second CD28 or 4-1BBz co-stimulatory domain, and a second signaling domain;
and wherein the first antibody binding domain and the second antibody binding domain are different from each other, and each bind to a different target,
wherein the wherein the targets of the first and second antibody binding domains irrespective of order are BCMA and CD19 or BCMA and CS-1, wherein the first and second co-stimulatory domains are intracellular,
and wherein the cleavage site is selected from the group consisting of porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), equine rhinitis A virus (ERAV) 2A (E2A), and FMDV 2A (F2A), and wherein said patient's autoimmune condition improves as a result of said depletion of antibody producing B cells and/or plasma cells.
Therefore, instant claim 1 is obvious variant of patent claim 4. More specifically, although patent claim 4 is not explicitly directed to a method of treating an autoimmune disease, the ordinary artisan would recognize that the depletion of antibody producing B cells and/or plasma cells in a patient with an autoimmune condition reads on the treatment of the autoimmune condition.
With that, instant claims 2-16 and 18-19 are known from the patent claims or prior art and can be further incorporated into the method rendered obvious by patent claim 4
16. Claims 1-16 and 18-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 12,275,787 B2. The reference patent is not afforded safe harbor under 35 USC 121 because the reference claims do not share continuity nor a restriction/speciation with the claims of the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claim renders obvious the instant claims. More specifically, the patented claim is not identical because no single patent claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patent claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 1 is directed to a method for treating an autoimmune disease, said method comprising administering to a patient in need thereof an ex vivo engineered T cell or NK cell co-expressing two distinct chimeric antigen receptor (CAR) units at the cell surface, wherein the engineered T cell or NK cell comprises a nucleotide sequence comprising from 5′ to 3′ a nucleotide encoding a promoter selected from human elongation factor-1 alpha (EF-1α) or spleen focus forming virus (SFFV), a first polynucleotide encoding a first chimeric antigen receptor polypeptide (CAR), a nucleotide encoding a first cleavage peptide, and a second polynucleotide encoding a second chimeric antigen receptor polypeptide (CAR), wherein the engineered cell further comprises a nucleotide encoding secreted IL-15/IL-15sushi or a functional fragment thereof, wherein the nucleotide encoding said enhancer is attached to the nucleotide encoding the first CAR or the nucleotide encoding the second CAR by a nucleotide encoding a second cleavage peptide that flanks either end of the two distinct encoded CAR units, wherein:
the first CAR comprises a first signal peptide, a first antibody binding domain, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and
the second CAR comprises a second signal peptide, a second antibody binding domain, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; and
wherein the first antibody binding domain and the second antibody binding domain are different and each bind to a different target, wherein the targets of the first and second antibody binding domains irrespective of order are CD19 and BMCA (CD269), wherein the first and second co-stimulatory domains are intracellular, and wherein the first and second cleavage peptides are selected from the group consisting of porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), equine rhinitis A virus (ERAV) 2A (E2A), and FMDV 2A (F2A), and wherein said autoimmune disease is systemic lupus erythematosus (SLE).
This therefore reads on the methods of instant claims 1 and 18-19.
With that, instant claims 2-16 are known from the patent claims or prior art and can be further incorporated into the method anticipated by patent claim 1.
17. Claims 1-16 and 18-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 29 of copending Application No.17/502,238 (reference number US 20220241327).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims renders obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Copending claim 29 is directed to a method for depleting B cell and plasma cells, the method comprising administering to a patient in need thereof a dual CAR, wherein the dual CAR binds to an antigen expressed on T- cells and an antigen on the surface of B-cells or plasma cells, wherein the antigen expressed on T cells is CD2, CD3, CD4, CD5, or CD7, and wherein the antigen on the surface of B cells or plasma cells is CD19, CD20, CD22, BCMA, CD38, CD138, CS1, or GPRC5D. This therefore reads on the methods of instant claims 1 and 4.
With that, instant claims 2-3, 5-16 and 18-19 are known from the copending claims or prior art and can be further incorporated into the method anticipated by copending claim 29.
This is a provisional nonstatutory double patenting rejection.
Conclusion
18. No claims are allowed.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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