DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 10/05/2023, is acknowledged.
3. Claims 1-5, 12-13, 15, 17-18, 22-24, 26, 28-29 and 31-34 are pending.
4. Applicant’s election without traverse of Group I, claims 1-5, 12-13, 15, 17-18 and 22-23 are directed to a regulatory T cell comprising an AP that specifically binds C4d and the species of (1) an scFv comprising (a) a VL of SEQ ID NO: 2 with the VL-CDR1-3 of SEQ ID NOs: 68-70 and b) a VH of SEQ ID NO: 4 with the VH-CDR1-3 of SEQ ID NO: 71-73, (2) a CAR comprising (a) a human CD8 hinge region (b) a CD28 transmembrane region, (c) a CD3 zeta cytoplasmic domain, and (d) a c-my tag, filed on 04/21/2026, is acknowledged.
5. Claims 24, 26, 28-29 and31-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Claims 1-5, 12-13, 17-18 and 22-23 are under examination as they read on a regulatory T cell comprising an AP that specifically binds C4d and the species of (1) an scFv comprising (a) a VL of SEQ ID NO: 2 with the VL-CDR1-3 of SEQ ID NOs: 68-70 and b) a VH of SEQ ID NO: 4 with the VH-CDR1-3 of SEQ ID NO: 71-73, (2) a CAR comprising (a) a human CD8 hinge region (b) a CD28 transmembrane region, (c) a CD3 zeta cytoplasmic domain, and (d) a c-my tag.
7. Applicant’s IDS, filed 07/20/2023, 10/05/2023, 03/07/2025 and 09/08/2025, is acknowledged.
8. The specification is objected to under 37CFR 1.821(d) for failing to recite the SEQ ID NOS. at [0011]-[0017].
9. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
10. Claims 1-5, 12-13, 17-18 and 22-23 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 encompasses a genus of a genetically modified regulatory T cell (Treg) comprising a genus of antigen binding proteins (ABP) that binds C4d.
Claim 2 encompasses a genus of chimeric antigen receptor (CAR).
Claim 3 encompasses a genus of scFv that binds to C4d.
Claim 4 encompasses a genus of ABP that binds C4d comprise less than the required 6 CDR, as well as up to 5 modifications in the L/H-CDRs.
Claim 5 encompasses a genus of ABP that binds C4d comprise up to 5% modification in in the H/L-CDRs of SEQ ID NOs: 2,4, 6, 8, 42, 47.
Claim 12 encompasses a genus of scFv comprising up to 20% modification in the CDRs of SEQ ID NO: 67, 83, 36.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of binding to C4d, inhibiting immune response, suppressing T cell proliferation, suppressing antibody-mediated rejection. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., 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, sufficient to show the applicant was in possession of the genus.
The specification at [0038] discloses that the term "antigen binding protein" (ABP) refers to a protein that specifically binds a target antigen, and includes antibodies, scFv's and CARs described herein. The term "antigen binding domain" refers to the portion of an antigen binding protein that specifically binds to a target antigen.
The specification at [0053] and FIG. 1A-1B discloses the production of anti-C4d CAR. FIG. 1A. Binding affinity of anti-C4d scFv clones (SC-8-Cκ, BF-2-Cκ) and control scFv clone (palivizumab-Cκ) to mouse C4d+Raji cells was measured by flow cytometric analysis.
[0128] Through the phage enzyme immunoassay with bio-panned scFv-displayed phage libraries, several reactive clones were identified as candidate clones. Two clones (SC-8, BF-2) which showed good binding affinity for C4d and the BF-2 clone were selected for further study based on its binding activity and expression level (FIG. 1A).
The specification discloses three antibody clones: N2-7, SC-8 and BF-2.
N2-7 has the LCDR1-3 of SEQ ID NOs: 43-44-45, HCDR1-3 of SEQ ID NO: 48-49-50, VL/VH of SEQ ID NO:42/47 and scFv of SEQ ID NO: 36.
BF-2 has the LCDR1-3 of SEQ ID NOs: 68-69-70, HCDR1-3 of SEQ ID NO: 71-72-73, VL/VH of SEQ ID NO:2/4 and scFv of SEQ ID NO: 67.
SC-8 has the LCDR1-3 of SEQ ID NOs: 84-85-86, HCDR1-3 of SEQ ID NO: 87-88-89, VL/VH of SEQ ID NO: 6/8 and scFv of SEQ ID NO: 83.
This case is akin to the case of Juno Therapeutics, Inc. v. Kite Pharma, Inc. In Juno v. Kite, the U.S. Court of Appeals for the Federal Circuit ruled that claims directed to a chimeric antigen receptor with a generic binding element with the function of “specifically interacts with a selected target” was not found to be supported under 35 U.S.C. 112(a) written description, as the specification only disclosed two scFv structures with this function that fell within the claimed genus of a “vast” number of additional binding elements.
The claims at issue in Juno v. Kite were directed to chimeric antigen receptors comprising generic “binding elements”, generic “scFv”, or generic scFvs that bind to CD19. The Court reiterated “[f]or genus claims using functional language, like the binding function of the scFvs claimed here, the written description “must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally- defined genus.” Ariad, 598 F.3d at 1349.” Id 1335.
The Court agreed with Kite, stating that the generic claims at issue broadly covered “any scFv for binding any target”, however the “written description fails to provide a representative sample of species within, or defining characteristics for, that expansive genus.” Additionally, “Juno argues these two working embodiments are representative of all scFvs in the context of a CAR. The evidence does not support Juno’s argument.” Id 1336.
The USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
In contrast to applicant’s reliance of describe the epitope of the C4d in providing a fully characterized antigen / specific epitope as well as claiming structural elements of the antigen, and inducing an immune response, suppressing T cell proliferation, suppressing antibody-mediated rejection, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-C4d antibodies to demonstrate possession.
Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
There is no evidence that knowledge of the chemical structure of an antigen gives the required kind of structure identifying information about the corresponding antibodies Applicants attempt to describe the invention by describing something that is not the invention: viz., the antigens to which the antibodies may bind. There nothing in the disclosure that describes the antibodies as required by the test set forth in Ariad.
However, the anti-C4d antibodies are required to practice the invention. The specification fails to provide any specific structural or physical information so as to define a genus of antibodies having the desired therapeutic properties. Applicant is merely rely on the identification of C4d as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. However, Federal Circuit clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017).
The claims are directed to a genus of anti-C4d antibodies. However, Federal Circuit clarification of the law of written description as it applies to antibodies. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-C4d antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e. the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
For instance, citing to Centocor, the Court analogized an antigen and antibody to a lock and a key. For an antigen where there is only a finite number of binding antibodies, discovering those antibodies may be routine and conventional, and description of the antigen alone may be sufficient. By contrast, for antigens with millions of keys, or millions of potentially binding antibodies, description of the antigen and even a couple of examples may be far from sufficient.
Artisans are well aware that knowledge of a given antigen (for instance C4d) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al (J Mol Biol. 2003 Nov 14;334(1): 103-18) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the FICDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document). Similarly, Lloyd et al (Protein Eng Des Sel. 2009 Mar;22(3):159-68) teach that a large majority of VH/VL germline gene segments are used in the antibody response to an antigen, even when the antibodies were selected by antigen binding, as their sequencing studies revealed that out of 841 unselected and 5,044 selected antibodies, all but one of the 49 functional VH gene segments was observed (see entire document). Goel et al (J Immunol. 2004 Dec 15; 173(12):7358-67) disclose the synthesis of three mAbs that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (see entire document). As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data such as that of Edwards et al. indicating the diversity of sequence bound in a population of antibodies that bind to a given antigen no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen. Indeed, Kanyavuz et al (Nat Rev Immunol. 2019 Jun; 19(6):355-368) teach that “Theoretically, under physiological conditions, the human immune system can generate BCRs with 1026 distinct sequences, an astronomical number that is far greater than the calculated number of all B cell clones that can be generated during the lifespan of a healthy human (estimated to be 4 x 1014).
The specification provides three anti-C4d antibodies, N2-7, SC-8 and BF-2, which were not random combinations of VH and VL i.e., they had specific VH domain (SEQ ID NO: 4, 8, 47) paired with specific VL domain (SEQ ID NO: 5, 4, 42, respectively). No other VH/VL domain was provided that mix the CDRH1 of SEQ ID NO: 48, 71, 87, CRRH2 of SEQ ID Nos:48, 72, 88 or CDRH3 of SEQ ID NO: 50, 73, 89 and CDRL1 of SEQ ID NO: 43, 68, 84, CDRL2 of SEQ ID NO: 44, 69, 85 and CDRL3 of SEQ ID NO: 45, 70, 86. The specification discloses only three species within the instant claim scope. The instant application encompasses (but does not exemplify) fragments and CDRs modification up to 20% (deletion/addition/substitution) to the claimed HCDRs and LCDRs of SEQ ID NOs: 43-45, 68-70, 84-86, 48-50, 71-73, 87-89. There is no teaching identifying what amino acids can be varied within the VH-CDRs and/or VL-CDRs antibody regions and still retain antibody or fragments capable of binding C4d. Brown et al (J. Immuno. 1996 May, 3285-91 at 3290 and Tables 1 and 2) describes how a one amino acid change in the VH CDR2 of a particular antibody was tolerated whereas, the antibody lost binding upon introduction of two amino changes in the same region. Vajdos et al. (J. Mol. Biol. 2002, Jul 5, 320(2):415-28 at 416) teach that amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. The scope of the claims encompasses antibodies with VH or VL that encompass variation (addition, deletion, substitution) in their CDRs. The prior art discloses that 6 CDRs as being essential structure of antibody's binding site, and thus when intact, would provide enough structure to define the antibody's binding site (structure/function correlation) e.g., where amino acid substitutions can be made so as to change (e.g. 6CDR's) or retain (e.g., constant or variable framework) antigen binding. Neither the prior art nor applicant's disclosure defines sufficient representative antibodies and/or sufficient structure/function correlation between modifying the VLCDRs or VHCDRs regions of the disclosed antibody and the retention of a specific binding antibody that binds the C4d to satisfy the WD requirement for the claims.
Neither the specification, nor the prior art provides any examples to support the premise of mixing and matching a HCDR or LCDR of the VH/VL of different antibodies would result in antigen binding. The prior art does not support a definition of an antibody structure by mixing and matching the HCDR1-3 sequence of a VH and LCDR of sequence of a VL and result in functional anti-C4d antibody. The specification fails to show that all HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 of the anti-C4d antibodies, N2-7, SC-8 and BF-2, are equivalent. The specification fails to establish that by replacing at least one CDR of N2-7 antibody with another CDR from SC-8 and BF-2, maintains C4d binding. Mixing and matching different the CDRs from different anti-C4d antibodies has not been shown to lead to Olfm binding. Such teachings were not made part of the specification at the time the invention was made.
The claims 4-5, 12 encompasses antibodies in which modification of the amino acids may vary in either or both the VH CDRs and/or VL CDRs region of SEQ ID NOs: 43-45, 68-70, 84-86, 48-50, 71-73, 87-89, via addition, deletion, substitution or insertion of one or more amino acids.
It is unlikely that antibodies or fragments thereof as defined by the claims which may contain less than the full complement of CDRs from the heavy and light chain variable regions of the N2-7, SC-8 and BF-2 antibodies fused to framework sequence, have the required binding function. The specification provides no direction or guidance regarding how to produce CAR as broadly defined by the claims. Undue experimentation would be required to produce the invention commensurate with the scope of the claims from the written disclosure alone. Further, the specification does not teach that a functional antibody can be obtained by replacing the CDR regions of an acceptor antibody with the less than all the 6 CDRs sequences of a donor antibody.
With respect to the recitation CAR comprising scFv which does not comprise all 6 CDRs of the antibody that is produced by N2-7, SC-8 and BF-2, the Examiner directs Applicant's attention to the training material given by Bennett Celsa, Example 2: (Ab genus: modified CDR's) slides 34-40. Example 2 of the Training material ((https://www.aipla.org/docs/default-source/committee-documents/bcp-files/2020/uspto-bcp-antibody-slides-final.pdf?sfvrsn=b377f2cc_0) which requires that the claims explicitly recite the binding antigen in addition to all 6 CDR regions for fulfillment of the written description requirements under § 112, 1. Slide 39 indicates that a claim encompasses antibodies with 6 intact CDRs as well as a subgenus of antibodies that encompass up to 10% variation (fragments and/or analogs) in the 6 CDRs lacks written description. Slide 40 provide the conclusion that, a single antibody species would not be deemed by one of skill in the art to be representative of a claim that defines an antibody that binds antigen X comprising at least 90% homology to the 6 CDR of the VH and VL chains.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
11. Claims are 1-5, 12-13, 17-18 and 22-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for A genetically modified regulatory T cell (Treg) comprising a chimeric antigen receptor (CAR) comprising a scFv that specifically binds C4d comprising SEQ ID NO: 67, 83, 36 , does not reasonably provide enablement for Genetically modified regulatory T cell recited in claims 1-5, 12-13, 17-18 and 22-23. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Claim 1 encompasses a genus of a genetically modified regulatory T cell (Treg) comprising a genus of antigen binding proteins (ABP) that binds C4d.
Claim 2 encompasses a genus of chimeric antigen receptor (CAR).
Claim 3 encompasses a genus of scFv that binds to C4d.
Claim 4 encompasses a genus of ABP that binds C4d comprise less than the required 6 CDR, as well as up to 5 modifications in the L/H-CDRs.
Claim 5 encompasses a genus of ABP that binds C4d comprise up to 5% modification in in the H/L-CDRs of SEQ ID NOs: 2,4, 6, 8, 42, 47.
Claim 12 encompasses a genus of scFv comprising up to 20% modification in the CDRs of SEQ ID NO: 67, 83, 36.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The claims are directed to a broad class of antibodies was that the class was defined by its function—the ability to bind to C4d and inhibiting immune response, suppressing T cell proliferation, suppressing antibody-mediated rejection. However, the specification did not give the skilled in the art enough information to choose candidate antibodies from millions of options and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.”
The specification discloses only three species of anti-C4d antibodies N2-7 has the LCDR1-3 of SEQ ID NOs: 43-44-45, HCDR1-3 of SEQ ID NO: 48-49-50, VL/VH of SEQ ID NO:42/47 and scFv of SEQ ID NO: 36. BF-2 has the LCDR1-3 of SEQ ID NOs: 68-69-70, HCDR1-3 of SEQ ID NO: 71-72-73, VL/VH of SEQ ID NO:2/4 and scFv of SEQ ID NO: 67. SC-8 has the LCDR1-3 of SEQ ID NOs: 84-85-86, HCDR1-3 of SEQ ID NO: 87-88-89, VL/VH of SEQ ID NO: 6/8 and scFv of SEQ ID NO: 83. While the claims are directed to a genus of millions of anti-C4d antibodies.
In Sanofi-Aventisub, the Federal Circuit relied on its prior precedential opinions when determining whether the full scope of a genus was enabled. These decisions included McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091 (Fed. Cir. 2020) (hereafter McRO); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380 (Fed. Cir. 2013) (hereafter Wyeth); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019) (hereafter Enzo); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149 (Fed. Cir. 2019) (hereafter Idenix).
The Federal Circuit, citing McRO, provided guidance on the application of enablement to genus claims, holding that “[a]lthough a specification does not need to describe how to make and use every possible variant of the claimed invention, when a range is claimed, there must be reasonable enablement of the scope of the range.” Sanofi-Aventisub, 987 F.3d at 1085 (internal quotations omitted). Additionally, the Federal Circuit characterized Wyeth as holding “that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality.” Id. at 1086. Similarly, the Federal Circuit characterized Enzo as holding “that the specification failed to teach one of skill in the art whether the many embodiments of the broad claims would exhibit that required functionality.” Id. Finally, the Federal Circuit characterized Idenix as affirming “the district court's determination that the claims had both structural and functional limitations, and that undue experimentation would have been required to synthesize and screen the billions of possible compounds because, given a lack of guidance across that full scope, finding functional compounds would be akin to finding a `needle in a haystack.' ” Id.
This case is akin to the issue in Sanofi-Aventisub, the court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a `vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. In the instant case, the specification discloses only three species that performed the claimed function by their amino acid sequences, with the claimed genus of millions different anti-C4d antibodies. The instant claims are directed to a class of anti-C4d antibodies that included “a `vast' number of additional antibodies” that the instant specification fails to describe their amino acid sequences.
The scope of the instant claims encompassed millions of antibodies and that it was necessary to first generate and then screen each candidate to determine whether it met the functional limitations. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
12. No claim is allowed.
13. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
Lee et al. Anti-C4d chimeric antigen receptor regulatory T cells suppressed allograft rejection in ABO-incompatible heart transplantation. Genes & Diseases, 9(1):1-4.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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July 10, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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