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Claims 1, 11, 13 – 14 and 17 – 27 were pending, with claims 19 – 25 withdrawn from consideration. Claims 1 and 27 have been amended, and claim 28 has been newly added. Claims 1, 11, 13 – 14 and 17 – 28 are currently pending with claims 19 – 25 withdrawn as being directed to nonelected subject matter. Claims 1, 11, 13 – 14, 17 – 18 and 26 – 28 are the subject of this Office Action.
Priority
The filing date of claims 1, 11, 13 – 14, 17 – 18, and 26 had been determined to be 07/24/2019.
Applicant’s arguments, including the Declaration by Dr. Mirjam Huberta Margaretha Heemskerk (“Heemskerk Declaration”) and the remarks of 02/17/2026, are insufficient to support the priority date of 03/10/2015 for the following reasons. Although it was known in the art how to identify the CDR regions in the TCR α/β at 03/10/2015, the TCRs are not disclosed the provisional application having the priority date of 03/10/2015 as presently claimed. The priority documents (with provisional application 62/130,884 having the earliest date of 03/10/2015) and the instant application did not originally disclose TCRs with CDR1s and CDR2s COMPRISING the CDR1s and CDR2s of the various TCRs. TCRs with CDR1s and CDR2s COMPRISING the CDR1s and CDR2s of the various TCRs are broader than simply the CDR1s and CDR2s that can be identified in the disclosed TCR sequences. Specifically the “comprising” language includes sequences beyond what is disclosed in the specific TCR sequences filed with the applications.
Additionally, the CDR3 of SEQ ID NO: 4 is not part of the TCRβ of SEQ ID NO: 10. SEQ ID NO: 4 is found in SEQ ID NOs: 19, 20 and 117. So the TCRβ of part b) is not supported by the instant application as filed nor the priority documents.
Thus, the priority documents don’t provide support for the claims as currently amended and the priority date of 7/24/2019 is maintained.
Claims 27 and 28 do find support in prior-filed Application No. 62/130,884, and thus, the effective filing date of present claims 27 and 28 is that of 62/130,884, which is 03/10/2015.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/06/2026 is in compliance with the provisions of 37 CFR 1.97 and ha8 considered by the examiner.
OBJECTIONS WITHDRAWN
Nucleotide and/or Amino Acid Sequence Disclosures
The claims were objected to because the CDRs appearing in claim 1 are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
In view of the claim amendments and the Heemskerk Declaration of 02/17/2026, this objection is withdrawn.
NEW REJECTIONS
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 11, 14, 17 – 18, 26 and 27 – 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) an isolated nucleic acid composition encoding a T cell receptor (TCR), wherein the TCR comprises: . . c) a first polypeptide comprising a TCRα polypeptide of the TCR, comprising: i) a CDR3 comprising SEQ ID NO: 49; and ii) a CDR1 comprising the CDR1 sequence of SEQ ID NO: 55 and a CDR2 comprising the CDR2 sequence of SEQ ID NO: 55; and a second polypeptide comprising a TCRP polypeptide of the TCR, comprising: i) a CDR3 comprising SEQ ID NO: 52; and ii) a CDR1 comprising the CDR1 sequence of SEQ ID NO: 58 and a CDR2 comprising the CDR2 sequence of SEQ ID NO: 58. The sequences of SEQ ID NOs: 55 and 58 are sequences of the human TCR without any modifications claimed. See Appendix.
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The recent Eligibility Guidance (2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance and 2018 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on January 7, 2019) address the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions). “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception.
In Prong One of Step 2A it is determined if the claim recites a judicial exception. If the claim recites a judicial exception, then Prong Two of Step 2A determines whether the claims recites additional elements that integrate the exception into a practical application.
If the answer to Prong Two of Step 2A is no, Step 2B is used to determine whether the claim as a whole amounts to significantly more than the exception by the recitation of additional elements.
The present claims are directed to a product so Step 1 is satisfied.
With respect to Step 2A MPEP 2106.04(c) II(C)(2) teaches:
In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. The patentee in Myriad had discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. As a result of their isolation, the isolated genes had a different structural characteristic than the natural genes, i.e., the natural genes had covalent bonds on their ends that connected them to the rest of the chromosome, but the isolated genes lacked these bonds. However, the claimed genes were otherwise structurally identical to the natural genes, e.g., they had the same genetic structure and nucleotide sequence as the BRCA genes in nature. The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977 ("Myriad's patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes … But isolation is necessary to conduct genetic testing") and 569 U.S. at 593, 106 USPQ2d at 1980 (describing how would-be infringers could not avoid the scope of Myriad’s claims). In sum, the claimed genes were different, but not markedly different, from their naturally occurring counterparts (the BRCA genes), and thus were product of nature exceptions.
In Ambry Genetics, the court identified claimed DNA fragments known as "primers" as products of nature, because they lacked markedly different characteristics. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014). The claimed primers were single-stranded pieces of DNA, each of which corresponded to a naturally occurring double-stranded DNA sequence in or near the BRCA genes. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because "single-stranded DNA cannot be found in the human body". The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers and their counterparts had the same genetic structure and nucleotide sequence. 774 F.3d at 760, 113 USPQ2d at 1243-44. The patentee also argued that the primers had a different function than when they are part of the DNA strand because when isolated as a primer, a primer can be used as a starting material for a DNA polymerization process. The court disagreed, because this ability to serve as a starting material is innate to DNA itself, and was not created or altered by the patentee:
In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction--a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here--the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.
Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, because the characteristics of the claimed primers were innate to naturally occurring DNA, they lacked markedly different characteristics from nature and were thus product of nature exceptions. A similar result was reached in Marden, where the court held a claim to ductile vanadium ineligible, because the "ductility or malleability of vanadium is . . . one of its inherent characteristics and not a characteristic given to it by virtue of a new combination with other materials or which characteristic is brought about by some chemical reaction or agency which changes its inherent characteristics". In re Marden, 47 F.2d 958, 959, 18 CCPA 1057, 1060, 8 USPQ 347, 349 (CCPA 1931
For Prong One of Step 2A the claims recite a judicial exception, i.e. a natural product which is a natural phenomenon. In particular, the claimed nucleic acid composition encoding a TCR encodes sequences of the natural human TCR, which are obtained from human patients. See Appendix for alignments with SEQ ID NOs: 55 and 58 and p. 105-lines 5-20 of the specification filed 8/10/2022. Thus, the answer to Prong One of Step 2A is yes, the claims do recite a judicial exception.
For Prong Two of Step 2A the claims do not integrate the exception into a practical application. The judicial exception is not integrated into a practical application because the additional limitation of “wherein the TCR specifically binds to a peptide-MHC complex, wherein the MHC molecule is an MHC class 1 HLA A2.01 molecule and the peptide is a preferentially expressed antigen in melanoma (PRAME) polypeptide; and wherein the PRAME polypeptide comprises SEQ ID NO: 89 for the TCR of a) and b) or SEQ ID NO:90 for the TCR of c)” of present claim 1 and a pharmaceutical composition of claim 18 is only suggestive of an intended use that does not change the structure or function of the TCR. Thus, the answer to Prong Two of Step 2A is no.
With respect to Step 2B MPEP 2106.05 (I) teaches that:
The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)).
An inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 573 U.S. at 21-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 78, 101 USPQ2d at 1968 (after determining that a claim is directed to a judicial exception, "we then ask, ‘[w]hat else is there in the claims before us?") (emphasis added)); RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"). Instead, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
With respect to Step 2B MPEP 2106.05 (d) teaches that:
Another consideration when determining whether a claim recites significantly more than a judicial exception is whether the additional element(s) are well-understood, routine, conventional activities previously known to the industry.
If the additional element (or combination of elements) is a specific limitation other than what is well-understood, routine and conventional in the field, for instance because it is an unconventional step that confines the claim to a particular useful application of the judicial exception, then this consideration favors eligibility. If, however, the additional element (or combination of elements) is no more than well-understood, routine, conventional activities previously known to the industry, which is recited at a high level of generality, then this consideration does not favor eligibility.
. . .
On the other hand, Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 67, 101 USPQ2d 1961, 1964 (2010) provides an example of additional elements that were not an inventive concept because they were merely well-understood, routine, conventional activity previously known to the industry, which were not by themselves sufficient to transform a judicial exception into a patent eligible invention. Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 79-80, 101 USPQ2d 1969 (2012) (citing Parker v. Flook, 437 U.S. 584, 590, 198 USPQ 193, 199 (1978) (the additional elements were "well known" and, thus, did not amount to a patentable application of the mathematical formula)). In Mayo, the claims at issue recited naturally occurring correlations (the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood that a drug dosage will be ineffective or induce harmful side effects) along with additional elements including telling a doctor to measure thiopurine metabolite levels in the blood using any known process. 566 U.S. at 77-79, 101 USPQ2d at 1967-68. The Court found this additional step of measuring metabolite levels to be well-understood, routine, conventional activity already engaged in by the scientific community because scientists "routinely measured metabolites as part of their investigations into the relationships between metabolite levels and efficacy and toxicity of thiopurine compounds." 566 U.S. at 79, 101 USPQ2d at 1968. Even when considered in combination with the other additional elements, the step of measuring metabolite levels did not amount to an inventive concept, and thus the claims in Mayo were not eligible. 566 U.S. at 79-80, 101 USPQ2d at 1968-69.
The additional limitations, such as a pharmaceutically acceptable carrier, do not change the structure or function of the TCR. Thus, the claimed TCR does not have a significantly different structure or function from the naturally-occurring human TCR and demonstrates that the recited products are not markedly different from what exists in nature.
REJECTIONS MAINTAINED IN MODIFIED FORM
Claim Rejections - 35 USC § 112
Claims 1, 11, 13 – 14, 17 – 18, and 26 were 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 1 recites CDRs that are not found in the present specification as recited in claim 1. Although CDR3 is disclosed in the specification, CDR1 and CDR2 and a TCR comprising them as broadly claimed are not disclosed as recited in claim 1. Thus the sequences, as recited in claim 1, lack support by the specification. Claims 11, 13 – 14, 17 – 18, and 26 depend from claim 1, either directly or indirectly, and thus inherit the deficiencies of claim 1.
Response to Arguments
On p. 7, fourth paragraph under the heading “The Rejection Under 35 U.S. C. $ 112(a) IS Traversed or Rendered Moot”, Applicant argues that “[t]he present application provides TCR a VJ region and TCR 3 VDJ region amino acid and nucleotide sequences, a and 3 CDR3 amino acid and nucleotide sequences, and TRAV and TRBV encoding genes for PRAME clones 54SLL, 46SLL and DSK3 QLL. See, for example, paragraph [0643] on page 64, pages 65-66, 69-70 and 74-75, Figures 17-19 and the corresponding legends at paragraphs [0025]-[0027] on page 2, and also paragraph [0616] of the published application. It was known by a person of ordinary skill in the art at the time the priority application was filed that the TCRa and TCR3 variable regions each include a CDR1, CDR2 and CDR3 region (as acknowledged at page 6 of the Office Action) and thus a corresponding CDR1, CDR2 and CDR3 sequence. See paragraph [0060] on page 5 of the U.S. publication; see also Heemskerk Declaration, paragraphs 8-9. The Heemskerk Declaration demonstrates that, as of the earliest priority date of the instant application, a person of ordinary skill in the art would have been able to identify the CDR1 and CDR2 region amino acid sequences of TCR a variable and TCR 3 variable region sequences.”
Applicant’s argument has been considered but not found persuasive because the CDR1 and CDR2, as claimed, is not supported by the present specification. For example, present claim 1 recites “a CDR1 of comprising the CDR1 sequence of SEQ ID NO: 31”. Although a TCR α or β is known in the art to include a CDR1, the boundaries of CDR1 in the sequence of SEQ ID NO: 31 must be defined by the claims or by the specification in order to comply with the written description requirement. Furthermore, the “comprising” language may include sequences beyond what is disclosed in the specific TCR sequences. Thus, it not clear what the exact structure of the CDRs are.
Points 11 – 13 of the Heemskerk Declaration provides an exemplary protocol to locate and identify CDR1 and CDR2 region sequences using full or partial variable region nucleotide sequences.
The points in the Declaration does not overcome the 112(a) written description rejection because the limitations of the claims must be supported by the specification-as-filed. Although the CDR1 and CDR2 sets of claim 1 may be obtained from programs that can identify them on the TCR sequence, the CDRs as claimed must be defined by the application-as-filed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 11, 13 – 14, 17 – 18, 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by HEEMSKERK (US 2016/0263155 A1, published 09/15/2016; See PTO-892: Notice of References Cited).
HEEMSKERK is directed to compositions and methods for inducing an immune response against the Preferentially Expressed Antigen of Melanoma (PRAME) and to methods for treating hyperproliferative diseases by inducing an immune response against PRAME antigen; the immune response may be induced by specifically targeting PRAME-expressing cells using T cell receptors directed against PRAME. See abstract.
Regarding claims 1 and 28, HEEMSKERK teaches SEQ ID NO: 31 and 34 with 100% identity. HEEMSKERK’s SEQ ID NO: 31 and 34 are identical to present claim 1’s SEQ ID NOs: 31 and 34 See Appendix.
Regarding claim 11, HEEMSKERK discloses nucleic acid further comprises a promoter operatively linked to the CDR3-encoding polynucleotide. See paragraph 042.
Regarding claims 13 and 14, HEEMSKERK discloses plasmid or viral vectors that comprise nucleic acid molecules and modified cells are provided that are transfected or transduced with a nucleic acid molecule. See paragraph 042.
Regarding claim 17, HEEMSKERK discloses that the modified cell is a T cell. See paragraph 41.
Regarding claim 18, HEEMSKERK discloses pharmaceutical compositions that comprise a modified cell of the present application, a nucleic acid of the present application, or a plasmid or viral vector of the present application, and a pharmaceutically acceptable carrier.
Regarding claim 26, HEEMSKERK discloses methods for expressing a T cell receptor that specifically binds to PRAME in a cell, comprising contacting a nucleic acid molecule of the present application with a cell under conditions in which the nucleic acid is incorporated into the cell, whereby the cell expresses the T cell receptor from the incorporated nucleic acid. See paragraph 0046.
Claims 1, 11, 14, 18 and 26 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by CHANG (WO 2019/231920-A1, filed 05/28/2019; see PTO-892: Notice of References Cited).
CHANG is directed to improvements on single-chain variable fragment (scFv) antibodies, multi- specific binding proteins, pharmaceutical compositions comprising such proteins, and therapeutic methods using such proteins and pharmaceutical compositions, including for the treatment of cancer. See abstract. CHANG teaches a protein comprising an antigen-binding T cell receptor (TCR) fragment (see claim 67 and paragraph 0018) and the nucleic acids expressing the protein (see paragraph 0062). CHANG teaches that the TCR fragment binds a PRAME peptide having the amino acid sequence presented by HLA-A2 (see claims 112 – 114). CHANG discloses a first polypeptide comprising the CDRs of part “a)” of present claim 1 and also discloses the second polypeptide with the CDRs of part “a)” of present claim 1. See Appendix.
CHANG teaches at paragraph [0038] In certain embodiments, the antigen-binding TCR fragment binds a PRAME peptide having the amino acid sequence of SEQ ID NO:347 presented by HLA-A2. In certain embodiments, the antigen-binding TCR fragment comprises an alpha chain variable domain related to SEQ ID NO:401 and a beta chain variable domain related to SEQ ID NO:402. SEQ ID NO:347 is QLLALLPSL the claimed SEQ ID NO: 90. See p. 67.
Thus, CHANG anticipates present claim 1.
Regarding claims 11, CHANG discloses expression vectors (see paragraph 0175), which would have promoters that allow the transcription of the nucleic acid.
Regarding claim 14 and 26, CHANG discloses that expression vectors can be stably transfected together into host cells to produce the multimeric proteins described. See paragraph 0175.
Regarding claim 18, CHANG discloses a pharmaceutical composition with a pharmaceutically acceptable carrier. See paragraphs 0096 – 0097.
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 13 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over CHANG (WO 2019/231920-A1, filed 05/28/2019; see PTO-892) as applied to claim 1, 11, 14, 18 and 26 above, and further in view of AMIR (Amir et al. Clin. Cancer Res. 2011 Sep 1; 17 (17): 5615-25; See PTO-892 of 03/21/2022).
The teachings of CHANG are discussed above and fully incorporated here.
AMIR is directed to T-cell receptors of PRAME-specific T cells and how they may be effective tools for adoptive T-cell therapy. See Abstract: Conclusions. AMIR teaches the PRAME polypeptide of SEQ ID NO: 89 (SLLQHLIGL). See Materials and Methods: Isolation and analysis of PRAME-specific T cells, p. 5616, right column – p. 5617, left column, first paragraph).
Regarding claims 13, AMIR teaches retroviral vector was constructed with a codon-optimized and cysteine-modified TCRα and TCRβ chain, which were expressed in T cells.. See TCR gene transfer, p. 5617, right column.
AMIR teaches an isolated plasmid or viral vector comprising an isolated nucleic acid composition encoding a TCR of PRAME-specific T cells expressed in T cells, and thus, it would have been obvious use the viral vector of AMIR because doing so is routine in the art as shown by AMIR.
Response to Arguments
On page 8, second paragraph under “The Rejections Under 35 U.S.C. & 102 Are Traversed or Rendered Moot” of the reply of 02/17/2026, Applicant argues that “Heemskerk is not prior art to the claimed invention. Heemskerk is the priority application for the instant application. The Patent Office already acknowledged that claim 27 is entitled to the priority to the March 10, 2015 filing date of the priority application. Therefore, this rejection at least does not apply to claim 27. In addition, the remaining rejected claims (claims 1, 11, 13-14, 17-18, and 26) also are supported and enabled by the priority applications.”
On page 9, first paragraph, Applicant also argues that “Chang was published in 2019. For at least the reasons discussed above, each of pending claims as amended are entitled to the priority of the March 10, 2015 filing date of the priority application. Accordingly, Chang is therefore not prior art to the pending claims as amended.”
Because present claims 27 and 28 are supported by the priority application having the 03/10/2015-filing date, the rejection over HEEMSKERK, which has a publication date of 09/15/2016, is withdrawn. However, present claims 1, 11, 13 – 14, 17 – 18, and 26 are not supported by the priority application, as discussed above, and thus have an effective filing date of 07/24/2019. Therefore, HEEMSKERK and CHANG, which has a publication date of 05/28/2019, are valid prior art over present claims 1, 11, 13 – 14, 17 – 18, 26 and 28.
On page 9, second paragraph under “The Rejections Under 35 U.S.C. & 103 Are Traversed or Rendered Moot”, Applicant argues that “[f]or at least the reasons discussed above, each of pending claims as amended are entitled to the priority of the March 10, 2015 filing date of the priority application. Accordingly, Chang is therefore not prior art to the pending claims as amended. Amir alone also does not render obvious the claimed invention as Amir was cited only for the concept of a plasmid or vector with a nucleic acid that encodes a TCR of PRAME-specific T cells. In addition, claim 13 provides an isolated plasmid or viral vector comprising the isolated nucleic acid composition of claim 1. The subject matter of claim 1 is novel and inventive. Accordingly, claim 13 should be considered novel and inventive.”
However, as discussed above, HEEMSKERK is valid prior art and anticipates independent claim 1. HEEMSKERK in view of AMIR renders the limitations of claim 13, which depends from claim 1, obvious for the reasons above and of record.
Conclusion
Claims 1, 11, 13 – 14, 17 – 18 and 26 – 28 are rejected.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment with SEQ ID NO: 55
TVAL2_HUMAN
ID TVAL2_HUMAN Reviewed; 113 AA.
AC A0A075B6T6;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=T cell receptor alpha variable 12-2 {ECO:0000303|Ref.2};
DE Flags: Precursor;
GN Name=TRAV12-2 {ECO:0000303|Ref.2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE TRAV12-2*01).
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2]
RP NOMENCLATURE.
RA Lefranc M.P., Lefranc G.;
RT "The T Cell Receptor FactsBook.";
RL (In) Lefranc M.P., Lefranc G. (eds.);
RL The T Cell Receptor FactsBook., pp.1-397, Academic Press, London. (2001).
RN [3]
RP REVIEW ON T CELL REPERTOIRE DIVERSITY.
RX PubMed=15040585; DOI=10.1038/nri1292;
RA Nikolich-Zugich J., Slifka M.K., Messaoudi I.;
RT "The many important facets of T-cell repertoire diversity.";
RL Nat. Rev. Immunol. 4:123-132(2004).
RN [4]
RP REVIEW ON T CELL RECEPTOR-CD3 COMPLEX ASSEMBLY, AND SUBCELLULAR LOCATION.
RX PubMed=20452950; DOI=10.1101/cshperspect.a005140;
RA Wucherpfennig K.W., Gagnon E., Call M.J., Huseby E.S., Call M.E.;
RT "Structural biology of the T-cell receptor: insights into receptor
RT assembly, ligand recognition, and initiation of signaling.";
RL Cold Spring Harb. Perspect. Biol. 2:A005140-A005140(2010).
RN [5]
RP REVIEW ON T CELL RECEPTOR SIGNALING.
RX PubMed=23524462; DOI=10.1038/nri3403;
RA Brownlie R.J., Zamoyska R.;
RT "T cell receptor signalling networks: branched, diversified and bounded.";
RL Nat. Rev. Immunol. 13:257-269(2013).
RN [6]
RP NOMENCLATURE.
RX PubMed=24600447; DOI=10.3389/fimmu.2014.00022;
RA Lefranc M.P.;
RT "Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise
RT of Immunoinformatics.";
RL Front. Immunol. 5:22-22(2014).
RN [7]
RP REVIEW ON FUNCTION.
RX PubMed=25493333; DOI=10.1146/annurev-immunol-032414-112334;
RA Rossjohn J., Gras S., Miles J.J., Turner S.J., Godfrey D.I., McCluskey J.;
RT "T cell antigen receptor recognition of antigen-presenting molecules.";
RL Annu. Rev. Immunol. 33:169-200(2015).
RN [8] {ECO:0007744|PDB:1AO7}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 23-112, AND DISULFIDE BONDS.
RX PubMed=8906788; DOI=10.1038/384134a0;
RA Garboczi D.N., Ghosh P., Utz U., Fan Q.R., Biddison W.E., Wiley D.C.;
RT "Structure of the complex between human T-cell receptor, viral peptide and
RT HLA-A2.";
RL Nature 384:134-141(1996).
RN [9] {ECO:0007744|PDB:4ZDH}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 24-112, AND DISULFIDE BONDS.
RA Singh N.K., Hossain M., Baker B.M.;
RT "Crystal structure of JKA6 TCR.";
RL Submitted (APR-2015) to the PDB data bank.
CC -!- FUNCTION: V region of the variable domain of T cell receptor (TR) alpha
CC chain that participates in the antigen recognition (PubMed:24600447).
CC Alpha-beta T cell receptors are antigen specific receptors which are
CC essential to the immune response and are present on the cell surface of
CC T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH)
CC complexes that are displayed by antigen presenting cells (APC), a
CC prerequisite for efficient T cell adaptive immunity against pathogens
CC (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates
CC TR-CD3 clustering on the cell surface and intracellular activation of
CC LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247
CC enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT,
CC which recruits numerous signaling molecules to form the LAT
CC signalosome. The LAT signalosome propagates signal branching to three
CC major signaling pathways, the calcium, the mitogen-activated protein
CC kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB)
CC pathways, leading to the mobilization of transcription factors that are
CC critical for gene expression and essential for T cell growth and
CC differentiation (PubMed:23524462). The T cell repertoire is generated
CC in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped
CC by intrathymic selection events to generate a peripheral T cell pool of
CC self-MH restricted, non-autoaggressive T cells. Post-thymic interaction
CC of alpha-beta TR with the pMH complexes shapes TR structural and
CC functional avidity (PubMed:15040585). {ECO:0000303|PubMed:15040585,
CC ECO:0000303|PubMed:23524462, ECO:0000303|PubMed:24600447,
CC ECO:0000303|PubMed:25493333}.
CC -!- SUBUNIT: Alpha-beta TR is a heterodimer composed of an alpha and beta
CC chain; disulfide-linked. The alpha-beta TR is associated with the
CC transmembrane signaling CD3 coreceptor proteins to form the TR-CD3 (TcR
CC or TCR). The assembly of alpha-beta TR heterodimers with CD3 occurs in
CC the endoplasmic reticulum where a single alpha-beta TR heterodimer
CC associates with one CD3D-CD3E heterodimer, one CD3G-CD3E heterodimer
CC and one CD247 homodimer forming a stable octomeric structure. CD3D-CD3E
CC and CD3G-CD3E heterodimers preferentially associate with TR alpha and
CC TR beta chains, respectively. The association of the CD247 homodimer is
CC the last step of TcR assembly in the endoplasmic reticulum and is
CC required for transport to the cell surface.
CC {ECO:0000303|PubMed:20452950}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000303|PubMed:20452950}.
CC -!- POLYMORPHISM: There are several alleles. The sequence shown is that of
CC IMGT allele TRAV12-2*01. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
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CC ---------------------------------------------------------------------------
DR EMBL; AC243980; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 1AO7; X-ray; 2.60 A; D=23-112.
DR PDB; 4ZDH; X-ray; 2.10 A; A=24-112.
DR PDB; 5E9D; X-ray; 2.51 A; D/I=22-112.
DR PDB; 5NHT; X-ray; 3.20 A; A=21-112.
DR PDB; 6DKP; X-ray; 2.97 A; D=22-113.
DR PDBsum; 1AO7; -.
DR PDBsum; 4ZDH; -.
DR PDBsum; 5E9D; -.
DR PDBsum; 5NHT; -.
DR PDBsum; 6DKP; -.
DR AlphaFoldDB; A0A075B6T6; -.
DR SMR; A0A075B6T6; -.
DR IMGT_GENE-DB; TRAV12-2; -.
DR GlyGen; A0A075B6T6; 1 site.
DR BioMuta; TRAV12-2; -.
DR MassIVE; A0A075B6T6; -.
DR MaxQB; A0A075B6T6; -.
DR PeptideAtlas; A0A075B6T6; -.
DR Ensembl; ENST00000390437.2; ENSP00000437362.1; ENSG00000211789.2.
DR UCSC; uc058zdt.1; human.
DR GeneCards; TRAV12-2; -.
DR HGNC; HGNC:12106; TRAV12-2.
DR HPA; ENSG00000211789; Tissue enriched (lymphoid).
DR neXtProt; NX_A0A075B6T6; -.
DR OpenTargets; ENSG00000211789; -.
DR VEuPathDB; HostDB:ENSG00000211789; -.
DR GeneTree; ENSGT00940000153130; -.
DR HOGENOM; CLU_077975_8_3_1; -.
DR OMA; QYSEKGP; -.
DR PhylomeDB; A0A075B6T6; -.
DR PathwayCommons; A0A075B6T6; -.
DR SignaLink; A0A075B6T6; -.
DR ChiTaRS; TRAV12-2; human.
DR Pharos; A0A075B6T6; Tdark.
DR PRO; PR:A0A075B6T6; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; A0A075B6T6; protein.
DR Bgee; ENSG00000211789; Expressed in granulocyte and 95 other tissues.
DR GO; GO:0042101; C:T cell receptor complex; IEA:UniProtKB-KW.
DR GO; GO:0042605; F:peptide antigen binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Receptor;
KW Reference proteome; Signal; T cell receptor.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..113
FT /note="T cell receptor alpha variable 12-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000443265"
FT DOMAIN 23..>113
FT /note="Ig-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..110
FT /evidence="ECO:0000269|PubMed:8906788,
FT ECO:0007744|PDB:1AO7, ECO:0007744|PDB:4ZDH"
Query Match 84.0%; Score 583; DB 2; Length 113;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
Qy 62 SGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAV 113
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAV 112
Alignment with SEQ ID NO: 58
A0A580_HUMAN
ID A0A580_HUMAN Unreviewed; 114 AA.
AC A0A580;
DT 28-NOV-2006, integrated into UniProtKB/TrEMBL.
DT 28-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE SubName: Full=T cell receptor beta variable 9 {ECO:0000313|Ensembl:ENSP00000488515};
DE SubName: Full=V_segment translation product {ECO:0000313|EMBL:AAC80194.1};
DE Flags: Fragment;
GN Name=TRBV9 {ECO:0000313|Ensembl:ENSP00000488515};
GN Synonyms=TCRBV1S1A1N1 {ECO:0000313|EMBL:AAC80194.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|EMBL:AAC80194.1};
RN [1] {ECO:0000313|EMBL:AAC80194.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=8020962; DOI=10.1006/geno.1994.1149;
RA Slightom J.L., Siemieniak D.R., Sieu L.C., Koop B.F., Hood L.;
RT "Nucleotide sequence analysis of 77.7 kb of the human V beta T-cell
RT receptor gene locus: direct primer-walking using cosmid template DNAs.";
RL Genomics 20:149-168(1994).
RN [2] {ECO:0000313|EMBL:AAC80194.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=8650574; DOI=10.1126/science.272.5269.1755;
RA Rowen L., Koop B.F., Hood L.;
RT "The complete 685-kilobase DNA sequence of the human beta T cell receptor
RT locus.";
RL Science 272:1755-1762(1996).
RN [3] {ECO:0000313|EMBL:AAC80194.1}
RP NUCLEOTIDE SEQUENCE.
RA Rowen L., Seto J., Smit A., Acharya C., Ahearn M.E., Ankener M., Baskin D.,
RA Bumgarner R., Chen L., Chen N., Deshpande P., Faust J., Howard S.,
RA Jerome N., Koop B.F., Lee H., Loretz C., Paeper B., Zackrone K., Hood L.;
RT "Sequence determination of the human T cell receptor beta locus: Strategy
RT and error analysis.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000313|EMBL:AAC80194.1}
RP NUCLEOTIDE SEQUENCE.
RA Rowen L., Wang K., Boysen C., Ahearn M.E., Charmley P., Paeper B., Lee I.,
RA Chen L., Trask B., Nickerson D., Seto D., Hood L.;
RT "Sequence variation among several haplotypes in the human T cell receptor
RT beta locus.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000313|Ensembl:ENSP00000488515, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6] {ECO:0000313|Ensembl:ENSP00000488515}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (AUG-2015) to UniProtKB.
RN [7] {ECO:0007829|PDB:5KS9, ECO:0007829|PDB:5KSA}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 22-114, AND DISULFIDE BONDS.
RX PubMed=27568928; DOI=10.1016/j.str.2016.07.010;
RA Petersen J., Kooy-Winkelaar Y., Loh K.L., Tran M., van Bergen J.,
RA Koning F., Rossjohn J., Reid H.H.;
RT "Diverse T cell receptor gene usage in HLA-DQ8-associated celiac disease
RT converges into a consensus binding solution.";
RL Structure 24:1643-1657(2016).
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC234635; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L36092; AAC80194.1; -; Genomic_DNA.
DR PDB; 5KS9; X-ray; 2.55 A; F/H=22-114.
DR PDB; 5KSA; X-ray; 2.00 A; D=22-114.
DR PDB; 5KSB; X-ray; 2.90 A; F/H=22-113.
DR PDBsum; 5KS9; -.
DR PDBsum; 5KSA; -.
DR PDBsum; 5KSB; -.
DR SMR; A0A580; -.
DR BioMuta; TRBV9; -.
DR PRIDE; A0A580; -.
DR Ensembl; ENST00000633328.1; ENSP00000488515.1; ENSG00000282204.1.
DR HGNC; HGNC:12246; TRBV9.
DR ChiTaRS; TRBV9; human.
DR Proteomes; UP000005640; Chromosome 7.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure {ECO:0007829|PDB:5KS9, ECO:0007829|PDB:5KSA};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW Signal {ECO:0000256|SAM:SignalP}.
FT SIGNAL 1..21
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 22..114
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5014564937"
FT DOMAIN 18..114
FT /note="Ig-like"
FT /evidence="ECO:0000259|PROSITE:PS50835"
FT DISULFID 42..110
FT /evidence="ECO:0007829|PDB:5KS9, ECO:0007829|PDB:5KSA"
FT NON_TER 114
FT /evidence="ECO:0000313|EMBL:AAC80194.1"
SQ SEQUENCE 114 AA; 12599 MW; 5861B9A6F3087FD4 CRC64;
Query Match 85.0%; Score 595; DB 38; Length 114;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQ 60
Qy 61 GLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASS 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASS 113
Alignment with SEQ ID NO: 31
RESULT 1
US-15-065-567-31
; Sequence 31, Application US/15065567
; Publication No. US20160263155A1
; GENERAL INFORMATION
; APPLICANT: LEIDEN UNIVERSITY MEDICAL CENTER
; TITLE OF INVENTION: T-CELL RECEPTORS DIRECTED AGAINST THE PREFERENTIALLY EXPRESSED
; TITLE OF INVENTION:ANTIGEN OF MELANOMA AND USES THEREOF
; FILE REFERENCE: BEL-2019-UT
; CURRENT APPLICATION NUMBER: US/15/065,567
; CURRENT FILING DATE: 2016-03-09
; PRIOR APPLICATION NUMBER: 62/130,884
; PRIOR FILING DATE: 2015-03-10
; NUMBER OF SEQ ID NOS: 117
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 31
; LENGTH: 131
; TYPE: PRT
; ORGANISM: Artificial Sequence
; FEATURE:
; OTHER INFORMATION: Description of Artificial Sequence: Synthetic
; OTHER INFORMATION:polypeptide
US-15-065-567-31
Query Match 100.0%; Score 693; DB 16; Length 131;
Best Local Similarity 100.0%;
Matches 131; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQDPGEG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQDPGEG 60
Qy 61 PVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGIPRDNYGQNFV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGIPRDNYGQNFV 120
Qy 121 FGPGTRLSVLP 131
|||||||||||
Db 121 FGPGTRLSVLP 131
Alignment with SEQ ID NO: 34
RESULT 1
US-15-065-567-34
; Sequence 34, Application US/15065567
; Publication No. US20160263155A1
; GENERAL INFORMATION
; APPLICANT: LEIDEN UNIVERSITY MEDICAL CENTER
; TITLE OF INVENTION: T-CELL RECEPTORS DIRECTED AGAINST THE PREFERENTIALLY EXPRESSED
; TITLE OF INVENTION:ANTIGEN OF MELANOMA AND USES THEREOF
; FILE REFERENCE: BEL-2019-UT
; CURRENT APPLICATION NUMBER: US/15/065,567
; CURRENT FILING DATE: 2016-03-09
; PRIOR APPLICATION NUMBER: 62/130,884
; PRIOR FILING DATE: 2015-03-10
; NUMBER OF SEQ ID NOS: 117
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 34
; LENGTH: 133
; TYPE: PRT
; ORGANISM: Artificial Sequence
; FEATURE:
; OTHER INFORMATION: Description of Artificial Sequence: Synthetic
; OTHER INFORMATION:polypeptide
US-15-065-567-34
Query Match 100.0%; Score 699; DB 16; Length 133;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYRQDPGL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYRQDPGL 60
Qy 61 GLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASTPWLAGGN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASTPWLAGGN 120
Qy 121 EQFFGPGTRLTVL 133
|||||||||||||
Db 121 EQFFGPGTRLTVL 133
Alignment with SIFNTLYKAGELCAGIPRDNYGQNFVFGPGTRLSVLP of part a) of present claim 1
RESULT 2
BHA45216
ID BHA45216 standard; protein; 118 AA.
XX
AC BHA45216;
XX
DT 23-JAN-2020 (first entry)
XX
DE Anti-PRAME TCR alpha chain variable domain, SEQ 401.
XX
KW PRAME protein; T cell receptor alpha; TCR alpha chain;
KW Tumor expressed melanoma antigen; antibody therapy; cancer; cell death;
KW cytostatic; prophylactic to disease; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2019231920-A1.
XX
CC PD 05-DEC-2019.
XX
CC PF 28-MAY-2019; 2019WO-US034186.
XX
PR 28-MAY-2018; 2018US-0677137P.
XX
CC PA (DRAG-) DRAGONFLY THERAPEUTICS INC.
XX
CC PI Chang GP, Cheung AF, Du J, Fallon D, Grinberg A, Haney W;
CC PI Oneil S, Wei R, Lunde BM, Prinz B;
XX
DR WPI; 2019-A2467A/97.
XX
CC PT Polypeptide for treating cancer, comprises single-chain variable fragment
CC PT linked to antibody constant domain by hinge, and single-chain variable
CC PT fragment comprises heavy chain variable domain and light chain variable
CC PT domain.
XX
CC PS Claim 113; SEQ ID NO 401; 141pp; English.
XX
CC The present invention relates to a novel polypeptide, useful for treating
CC cancer in a subject. The polypeptide comprises a single-chain variable
CC fragment (scFv) linked to an antibody constant domain via a hinge, where
CC the scFv comprises a heavy chain variable region (VH) and light chain
CC variable region (VL) with their corresponding complementarity determining
CC regions (CDRs). The invention further claims: (1) a formulation
CC comprising the novel polypeptide; (2) a cell comprising one or more
CC nucleic acids encoding a protein; (3) a method for enhancing tumor cell
CC death; and (4) a method for treating cancer by administering the novel
CC polypeptide or formulation to a patient. The polypeptide preferably
CC antibody and formulation comprising the antibody are useful for treating
CC or preventing cancer such as acute myeloid leukemia, acute myelomonocytic
CC leukemia, B cell lymphoma, bladder cancer, breast cancer, colorectal
CC cancer, diffuse large B cell lymphoma esophageal cancer, ewings sarcoma,
CC follicular lymphoma, gastric cancer, gastrointestinal cancer,
CC gastrointestinal stromal tumors, glioblastoma, head and neck cancer,
CC melanoma, mesothelioma, multiple myeloma, myelodysplastic syndrome, renal
CC cell carcinoma, neuroblastoma, non-small cell lung cancer, neuroendocrine
CC tumors, ovarian cancer, pancreatic cancer, prostate cancer, sarcomas,
CC small cell lung cancer, T cell lymphoma, testis cancer, thymic carcinoma,
CC thyroid cancer, urothelial cancer, cancers infiltrated by myeloid-derived
CC suppressor cells, cancers with extracellular matrix deposition, cancers
CC with high levels of reactive stroma, and cancers with neoangiogenesis.
XX
SQ Sequence 118 AA;
Query Match 77.4%; Score 154; Length 118;
Best Local Similarity 42.5%;
Matches 37; Conservative 0; Mismatches 0; Indels 50; Gaps 2;
Qy 1 SIFNT-----------------LYKAGEL------------------------------- 12
||||| |||||||
Db 27 SIFNTWLWYKQDPGEGPVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGI 86
Qy 13 --CAGIPRDNYGQNFVFGPGTRLSVLP 37
|||||||||||||||||||||||||
Db 87 YFCAGIPRDNYGQNFVFGPGTRLSVLP 113
Alignment with MDHENSYDVKMCASTPWLAGGNEQFFGPGTRLTVL of part a) of present claim 1
BHA45217
ID BHA45217 standard; protein; 121 AA.
XX
AC BHA45217;
XX
DT 23-JAN-2020 (first entry)
XX
DE Anti-PRAME TCR beta chain variable domain, SEQ 402.
XX
KW PRAME protein; T cell receptor beta; TCR beta chain;
KW Tumor expressed melanoma antigen; antibody therapy; cancer; cell death;
KW cytostatic; prophylactic to disease; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2019231920-A1.
XX
CC PD 05-DEC-2019.
XX
CC PF 28-MAY-2019; 2019WO-US034186.
XX
PR 28-MAY-2018; 2018US-0677137P.
XX
CC PA (DRAG-) DRAGONFLY THERAPEUTICS INC.
XX
CC PI Chang GP, Cheung AF, Du J, Fallon D, Grinberg A, Haney W;
CC PI Oneil S, Wei R, Lunde BM, Prinz B;
XX
DR WPI; 2019-A2467A/97.
XX
CC PT Polypeptide for treating cancer, comprises single-chain variable fragment
CC PT linked to antibody constant domain by hinge, and single-chain variable
CC PT fragment comprises heavy chain variable domain and light chain variable
CC PT domain.
XX
CC PS Claim 113; SEQ ID NO 402; 141pp; English.
XX
CC The present invention relates to a novel polypeptide, useful for treating
CC cancer in a subject. The polypeptide comprises a single-chain variable
CC fragment (scFv) linked to an antibody constant domain via a hinge, where
CC the scFv comprises a heavy chain variable region (VH) and light chain
CC variable region (VL) with their corresponding complementarity determining
CC regions (CDRs). The invention further claims: (1) a formulation
CC comprising the novel polypeptide; (2) a cell comprising one or more
CC nucleic acids encoding a protein; (3) a method for enhancing tumor cell
CC death; and (4) a method for treating cancer by administering the novel
CC polypeptide or formulation to a patient. The polypeptide preferably
CC antibody and formulation comprising the antibody are useful for treating
CC or preventing cancer such as acute myeloid leukemia, acute myelomonocytic
CC leukemia, B cell lymphoma, bladder cancer, breast cancer, colorectal
CC cancer, diffuse large B cell lymphoma esophageal cancer, ewings sarcoma,
CC follicular lymphoma, gastric cancer, gastrointestinal cancer,
CC gastrointestinal stromal tumors, glioblastoma, head and neck cancer,
CC melanoma, mesothelioma, multiple myeloma, myelodysplastic syndrome, renal
CC cell carcinoma, neuroblastoma, non-small cell lung cancer, neuroendocrine
CC tumors, ovarian cancer, pancreatic cancer, prostate cancer, sarcomas,
CC small cell lung cancer, T cell lymphoma, testis cancer, thymic carcinoma,
CC thyroid cancer, urothelial cancer, cancers infiltrated by myeloid-derived
CC suppressor cells, cancers with extracellular matrix deposition, cancers
CC with high levels of reactive stroma, and cancers with neoangiogenesis.
XX
SQ Sequence 121 AA;
Query Match 76.2%; Score 148.5; Length 121;
Best Local Similarity 39.8%;
Matches 35; Conservative 0; Mismatches 0; Indels 53; Gaps 2;
Qy 1 MDHEN-----------------SYDVKM-------------------------------- 11
||||| ||||||
Db 27 MDHENMFWYRQDPGLGLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQT 86
Qy 12 ----CASTPWLAGGNEQFFGPGTRLTVL 35
||||||||||||||||||||||||
Db 87 SMYLCASTPWLAGGNEQFFGPGTRLTVL 114
Prosecution Insights