DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a continuation of US Application No. 17/049239, filed 16 October 2020 (now US Patent No. 12077774 B2, filed 03 September 2024), which is a national stage entry under 35 USC 371 of PCT/GB2019/051098, filed 17 April 2019. Acknowledgment is made of Applicant’s claim for foreign priority under 119(a)-(d) or (f) to United Kingdom Application Nos. GB1806330.5 and GB1806331.3, each filed 18 April 2018. Accordingly, receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 filed in parent Application No. 17/049239.
Status of the Claims
Applicant’s preliminary submission filed 05 August 2024 has been entered. Claims 28-47 are pending. Claims 1-27 have been cancelled without prejudice or disclaimer and claims 28-47 have been newly added. Therefore, prosecution on the merits commences for claims 28-47.
Specification
The disclosure is objected to for referencing colors within the figures, when colored drawings have not been submitted in the application. More specifically, the Specification references colors at least within Pages 4-5 and 31 in reference to Figures 1-4 and 7-8. Applicant is requested to review the Specification to identify any additional references to colors within the drawings and delete as appropriate since black and white drawings are submitted. The Specification must be amended to delete reference to specific colors within the text of the Specification.
Appropriate correction is required.
Claim Objections
Claims 30-31, 39, 42-44, and 47 are objected to because of the following informalities:
Regarding claims 30-31: The instant claims are each objected to for reciting “wherein the disease is selected from” instead of “wherein the disease is selected from the group consisting of”. See MPEP § 2117.
Appropriate correction is required.
Regarding claim 39: The instant claim is objected to for reciting “A method according to claim 35” instead of “[[A]]The method according to claim 35”.
Appropriate correction is required.
Regarding claims 42-43: The instant claims are each objected to for reciting “An engineered Treg according to claim 41” instead of “[[An]]The engineered Treg according to claim 41”.
Appropriate correction is required.
Regarding claim 44: The instant claim is objected to for reciting “comprising an engineered Treg according to claim 41” instead of “ comprising [[an]]the engineered Treg according to claim 41”.
Appropriate correction is required.
Regarding claim 47: The instant claim is objected to for reciting “A method according to claim 46” instead of “[[A]]The method according to claim 46”.
The instant claim is also objected to for reciting “wherein the disease is selected from” instead of “wherein the disease is selected from the group consisting of”. See MPEP § 2117.
Appropriate correction is required.
Claim Interpretation
Under the broadest reasonable interpretation of each claim, all of the “optional” limitations are not required.
Furthermore, instant claim 40 is directed to a product which utilizes product-by-process language. The limitations of the process of production are considered only in so far as the process of production imparts distinct structural or chemical characteristics or properties to the claimed product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP § 2113.
Claim 40 defines the method in which an engineered Treg is obtained, wherein the method comprises introducing into the Treg an expression vector which comprises a nucleic acid comprising (i) a polynucleotide encoding a FOXP3 polypeptide and (ii) a polynucleotide encoding an exogenous T cell receptor (TCR) or a polynucleotide encoding a chimeric antigen receptor (CAR), wherein the nucleic acid has the orientation: 5' FOXP3 - TCR/CAR 3' and wherein the ability of the Treg to suppress immune responses is enhanced. In the instant case, there is no evidence that the preparation method imparts any particular structure or significance to the Tregs other than requiring the Treg to comprise (i) an exogenous FOXP3 polypeptide and (ii) an exogenous TCR or CAR.
Therefore, claim 40 will be interpreted as if Tregs obtained by any method fulfills the limitation detailed in the instant claim, so long as the Treg comprises (i) an exogenous FOXP3 polypeptide and (ii) an exogenous TCR or CAR.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 28 and 32-34 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 the prevention or treatment of autoimmune diseases, inflammatory CNS diseases, and diseases associated with transplant rejection, does not reasonably provide enablement for the prevention or treatment of any disease using the claimed method. The instant 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.
Possession of an invention may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998). Although working examples are not required, the claimed invention is required to be enabled so that any person skilled in the art can make and use the invention without undue experimentation. See MPEP § 2164.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP § 2164.01.
Nature of the invention: Independent claim 28 is directed to a method of treating or preventing a disease, said method comprising administering to a subject in need thereof a pharmaceutical composition comprising an engineered regulatory T cell (Treg) with an enhanced ability to suppress immune responses obtained by a process comprising: (i) isolating a CD4+CD25+CD127-/lowCD45RA+ Treg from a cell population; and (ii) introducing a polynucleotide encoding a FOXP3 polypeptide into the isolated CD4+CD25+CD127-/lowCD45RA+ Treg to enhance the ability of the Treg to suppress immune responses.
The relative skill of those in the art: The relative skill of those in the art is high, with the majority of ordinary artisans possessing an advanced degree.
The breadth of the claims: With respect to claim breadth, the standard under 35 U.S.C. §112(a) entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing for enablement, the claims are analyzed with respect to the teachings of the Specification and are to be “given their broadest reasonable interpretation consistent with the Specification.” See MPEP § 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the Examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
As such, the broadest reasonable interpretation of the instantly claimed methods allows for the prevention or treatment of any disease in any subject using a pharmaceutical composition comprising engineered Tregs with an enhanced ability to suppress immune responses. A skilled artisan would not know how to treat a subject with a reasonable expectation of success based solely on what is disclosed in the Specification.
The amount of direction or guidance presented: The instant Specification provides limited guidance for the prevention or treatment of all diseases. Instead, the instant disclosure provides exemplary autoimmune diseases, inflammatory CNS diseases, and diseases associated with transplant rejection – particularly, graft-vs-host disease, multiple sclerosis, systemic lupus erythematosus, sarcoidosis, Behcet disease, juvenile idiopathic arthritis, scleroderma, Sjogren syndrome, Alzheimer's Disease, Parkinson's disease, neurotropic viral infections, stroke, paraneoplastic disorders and traumatic brain injury. See, for example, Pages 26-28 of the instant Specification filed 02 August 2024. This fails to provide specific details necessary to successfully perform the full scope of the claimed method.
The presence or absence of working examples: The instant Specification has not provided any working examples for the treatment of diseases using the pharmaceutical composition, instead providing working examples to measure the engraftment of TCR+FOXP3 transduced Thy1.1+CD4+CD25+ Tregs within HLA-DRB*0401 transgenic hosts. See Example 6, which correlates to Pages 32-33 of the instant Specification. Therefore, Applicant has not provided sufficient evidence of the prevention or treatment of any disease in any subject using a pharmaceutical composition comprising engineered Tregs with an enhanced ability to suppress immune responses.
The level of predictability in the art and quantity of experimentation necessary: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention.
The prior art appears to be undecided on the utilization of Tregs for the treatment of a broad range of diseases given the unpredictable immune effects. More specifically, the disclosure of Taams et al (Immunology, 2006) teaches that the administration of Tregs has the potential to spread undesired immunosuppression and thereby induce other unrelated immune pathologies (Pages 1, 3-4, 6; Table 1).
Therefore, the full scope of the claim is thus not enabled in regards to the prevention or treatment of any disease in any subject using pharmaceutical composition comprising engineered Tregs with an enhanced ability to suppress immune responses, since at best it would require undue trial and error experimentation.
Instant claims 32-34 are included within the rejection because they fail to correct the deficiencies of their parent claim.
Claims 32, 36, and 42 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 claims 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 inventors, at the time the application was filed, had possession of the claimed invention.
The claims under rejection are directed, in part, to methods of treating or preventing a disease (claim 32), or enhancing the ability of a Treg to suppress immune responses (claim 36), wherein the methods comprise introducing a polynucleotide encoding a FOXP3 polypeptide into an isolated CD4+CD25+CD127-/lowCD45RA+ Treg, wherein the FOXP3 polypeptide comprises an amino acid sequence which is at least 80% identical to SEQ ID NO: 3 or 4 or a functional fragment thereof, or wherein the polynucleotide encoding the FOXP3 polypeptide comprises a polynucleotide sequence which is at least 80% identical to SEQ ID NO: 1 or 2 or a functional fragment thereof (emphasis added).
Likewise, the claims under rejection are directed, in part, to an engineered Treg (claim 42) comprising an exogenous polynucleotide encoding a FOXP3 polypeptide, wherein the FOXP3 polypeptide comprises an amino acid sequence which is at least 80% identical to SEQ ID NO: 3 or 4 or a functional fragment thereof, or wherein the polynucleotide encoding the FOXP3 polypeptide comprises a polynucleotide sequence which is at least 80% identical to SEQ ID NO: 1 or 2 or a functional fragment thereof (emphasis added).
Thus, to satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed group – or genus – of functional fragments, it must be clear that: (1) the identifying characteristics of the claimed functional fragments have been disclosed, e.g., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed cor-relation between function and structure, or by a com-bination 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 ‘functional fragment [of FOXP3]’ its broadest reasonable interpretation, the number and types of polypeptides or polynucleotides which can be considered a functional fragment of FOXP3 is extraordinarily great, and can be interpreted to even include a single amino acid. Applicant’s disclosure does not provide any exemplary functional fragments, instead broadly stating within Pages 12-15 of the instant Specification that the Treg can comprise FOXP3 polypeptides or polynucleotides or functional fragments thereof. Therefore, there is minimal disclosure of acceptable functional fragments of FOXP3.
Regarding disclosure of identifying characteristics of the claimed functional fragments, a review of the Specification fails to provide a definition of the structural characteristics the functional fragments encompassed by the current claims must have in regards to FOXP3. 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 FOXP3 which must be shared by all functional fragments thereof; and thus one of ordinary skill in the art would not immediately envisage all functional fragments of FOXP3 as currently claimed. Therefore, Applicant has not disclosed the identifying characteristics of the claimed functional fragments.
Regarding disclosure of a representative number of species within the genus, a review of the Specification shows that Applicant has not disclosed any acceptable functional fragments of FOXP3. This lack of disclosure evidently does not constitute a representative number for such a broad genus as is encompassed by the breadth of ‘functional fragments of FOXP3’. Therefore, Applicant has not disclosed a representative number of species, as would be required to support description and to show possession of each 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, claims 144-145 are considered to lack sufficient written description and are properly rejected under 35 USC 112(a).
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.
Claims 30, 32, 36, 38, 42, and 47 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.
Regarding claim 30: The instant claim further defines the disease as being “selected from an autoimmune disease, transplant rejection or graft-vs-host disease” (emphasis added). Claim language defined by a Markush grouping requires selection from a closed group "consisting of" the alternative members. See MPEP § 2117(I): Id. at 1280, 67 USPQ2d at 1196. The recitation of “or” indicates that the Markush group is open, thus rendering the metes and bounds of the claim indefinite.
Appropriate correction is required.
Regarding claims 32, 36, and 42: The instant claims each recite the limitation “wherein: (i) the FOXP3 polypeptide comprises an amino acid sequence which is at least 80% identical to SEQ ID NO: 3 or 4 or a functional fragment thereof; or (ii) the polynucleotide encoding the FOXP3 polypeptide comprises a polynucleotide sequence which is at least 80% identical to SEQ ID NO: 1 or 2 or a functional fragment thereof.” The scope of the claim is unclear, as it is uncertain if Applicant is requiring the FOXP3 polypeptide or polynucleotide thereof to be at least 80% identical to the functional fragments of the listed sequence identifies or the full-length listed sequence identifiers, or rather if the FOXP3 polypeptide, polynucleotide, and functional fragments thereof are at least 80% identical to the listed sequence identifiers. Therefore, the metes and bounds of the claims cannot be determined, thus rendering the claims indefinite.
Appropriate correction is required.
Regarding claim 38: The instant claim recites the terms “preferably” in Line 9. In the instant case, the term “preferably” is being treated as exemplary language. Therefore, the exemplary term “preferably” renders the instant claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d). For the sake of compact prosecution, the instant claim is interpreted as if the ”preferable” language is not required.
Appropriate correction is required.
Regarding claim 47: The instant claim further defines the disease as being “selected from an autoimmune disease, transplant rejection, graft-vs-host disease and/or from multiple sclerosis, systemic lupus erythematosus, sarcoidosis, Behcet disease, juvenile idiopathic arthritis, scleroderma, Sjogren syndrome, Alzheimer's Disease, Parkinson's disease, neurotropic viral infections, stroke, paraneoplastic disorders and traumatic brain injury” (emphasis added). Claim language defined by a Markush grouping requires selection from a closed group "consisting of" the alternative members. See MPEP § 2117(I): Id. at 1280, 67 USPQ2d at 1196. The recitation of “or” indicates that the Markush group is open, thus rendering the metes and bounds of the claim indefinite.
Appropriate correction is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 40 is rejected under 35 U.S.C. 102(a)(2) as being anticipated by Maus et al (US 2020/0330515 A1). Maus et al has an effective filing date of 17 October 2017.
Maus et al disclose engineered regulatory T cells (Tregs) and pharmaceutical compositions thereof, wherein the Tregs are engineered to promote or increase their immunosuppressive activity (Abstract; Paragraphs [0058], [0204]). Maus et al further disclose that engineered Tregs express an exogenous FoxP3 polypeptide or an exogenous nucleic acid encoding the FoxP3 polypeptide, and are further engineered to comprise a nucleic acid encoding a chimeric antigen receptor (CAR) polypeptide (Paragraphs [0039], [0043], [0069], [0200], [0207], [0315]; Figure 3).
Accordingly, Maus et al anticipate the claims as follows:
Regarding claim 40: The instant claim recites a product-by-process limitation, as indicated in the Claim Interpretation section above, which is incorporated herein in its entirety. Accordingly, so long as the resulting Treg expresses (i) an exogenous FOXP3 polypeptide and (ii) an exogenous TCR or CAR, the method by which the Tregs are obtained does not further limit the claims.
Following that interpretation, Maus et al disclose a Treg that has been engineered to express an exogenous FoxP3 polypeptide and a CAR. This therefore reads on the engineered Treg of the instant claim.
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 35-39 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Maus et al (US 2020/0330515 A1) as evidenced by NCBI (forkhead box protein P3 isoform a [Homo sapiens], 2023).
Maus et al is considered prior art under 35 USC 102(a)(2), with an effective filing date of 17 October 2017.
Regarding claims 35 and 45: Maus et al disclose engineered regulatory T cells (Tregs), wherein the Tregs are engineered to promote or increase their immunosuppressive activity (Abstract; Paragraphs [0058], [0184], [0204]).
As such, Maus et al disclose that the engineered Tregs express an exogenous FoxP3 polypeptide or an exogenous nucleic acid encoding the FoxP3 polypeptide (Paragraphs [0039], [0043], [0200], [0204], [0315]). Maus et al further disclose that the engineered Treg cells can also comprise a nucleic acid encoding a chimeric antigen receptor (CAR) polypeptide, wherein a CAR 28ζ FoxP3 construct comprises an anti-CD19 CAR and a FoxP3 transgene – oriented 5’ to 3’, respectively – within a single lentiviral backbone (Paragraphs [0069], [0093], [0205]-[0209], [0315], [0359]; Figures 3, 23A).
Maus et al further disclose that the engineered Tregs can be administered to a patient in need thereof, including those suffering from an autoimmune condition or allograft rejection (Paragraphs [0012]-[0021], [0059]-[0065], [0150], [0215]-[0220]).
Maus et al do not disclose that the Tregs are transduced with a lentiviral vector comprising the FoxP3 transgene 5’ to the CAR, as required by instant claims 35 and 45.
However, it would have been prima facie obvious to have modified the method of Maus et al such that the Tregs are engineered with a lentiviral construct comprising the FoxP3 transgene 5’ to the CAR. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to rearrange the lentiviral construct such that the FoxP3 polypeptide is 5’ to the anti-CD19 CAR, as it would have ensured that the CAR expression only occurs – or is induced – by the expression of FoxP3 (Paragraph [0208]), and would have had a reasonable expectation of success based on the experimental protocols outlined in Maus et al regarding the engineering of Tregs (Paragraphs [0069], [0207], [0314]-[0315], [0369]). See MPEP § 2143(I)(G).
Consequently, Maus et al render obvious a method wherein Tregs are engineered to express a lentiviral construct respectively comprising from 5’ to 3’ a FoxP3 transgene and an anti-CD19 CAR. As the engineered Tregs have an enhanced ability to suppress immune responses (claim 35) and can be administered to subjects suffering from an autoimmune condition or allograft rejection (claim 45), this therefore renders obvious the methods of the instant claims.
Regarding claim 36: Following the discussion of claim 35, Maus et al further disclose that the exogenous FoxP3 polypeptide is that detailed in NCBI Gene ID: 50943 (Paragraph [0204]). The polypeptide sequence of NCBI Gene ID: 50943 has 100% identity to instant SEQ ID NO: 3, as shown in the sequence alignment at the end of the document (NCBI, forkhead box protein P3 isoform a [Homo sapiens]). This therefore reads on the method of the instant claim.
Regarding claims 37-38: Following the discussion of claim 35, Maus et al further disclose that CD4+ T cells are first isolated from healthy donor samples, enriched for CD25+ cells, and subsequently purified for Tregs expressing CD4+ CD8− CD25++ CD127low via fluorescence activated sorting (FACS) (claim 38) (Paragraphs [0036], [0057], [0088], [0198]-[0199], [0314]). From there, Maus et al disclose that the purified Tregs are then engineered to express an exogenous FoxP3 polypeptide or an exogenous nucleic acid encoding the FoxP3 polypeptide (Paragraphs [0039], [0043], [0056], [0200], [0204]-[0205], [0275], [0315]). This therefore reads on the method of instant claim 37.
Regarding claim 39: Following the discussion of claim 35, Maus et al further disclose that the FoxP3 transgene and anti-CD19 CAR are separated by a T2A self-cleaving sequence (Paragraphs [0069], [0315], [0359]-[0360]; Figure 3). This therefore reads on the method of the instant claim.
Claims 28-34 and 41-47 are rejected under 35 U.S.C. 103 as being unpatentable over Maus et al (US 2020/0330515 A1) as evidenced by NCBI (forkhead box protein P3 isoform a [Homo sapiens], 2023) in view of Horneo et al (Transplantation, 2016, of record on IDS filed 07 January 2026).
The discussion of Maus et al regarding claim 45 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Maus et al renders obvious independent
claim 45. Horneo et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 28, 30, and 33-34: Maus et al disclose engineered regulatory T cells (Tregs), wherein the Tregs are engineered to promote or increase their immunosuppressive activity (Abstract; Paragraphs [0058], [0184], [0204]).
As such, Maus et al disclose that CD4+ T cells are first isolated from healthy PBMC donor samples, enriched for CD25+ cells, and subsequently purified for Tregs expressing CD4+ CD8− CD25++ CD127low via fluorescence activated sorting (FACS) (Paragraphs [0036], [0057], [0088], [0198]-[0199], [0314]). From there, Maus et al disclose that the purified Tregs are then engineered to express an exogenous FoxP3 polypeptide or an exogenous nucleic acid encoding the FoxP3 polypeptide (Paragraphs [0039], [0043], [0056], [0200], [0204]-[0205], [0275], [0315]).
Maus et al further disclose that the purified Treg cells can also be engineered to comprise a nucleic acid encoding a chimeric antigen receptor (CAR) polypeptide, wherein a CAR 28ζ FoxP3 construct comprises an anti-CD19 CAR and a FoxP3 transgene – oriented 5’ to 3’, respectively – within a single lentiviral backbone (Paragraphs [0069], [0093], [0204]-[0209], [0278]-[0279], [0315], [0359]; Figures 3, 23A).
Maus et al further disclose that the purified Tregs can be further sorted based on the positive expression of CD45RA and engineered to express first-generation and second-generation anti-CD19 chimeric antigen receptors (CARs) (Paragraphs [0132], [0369]; Figure 35F). It is of note that, in the event that the effective filing date of Maus et al does not cover the manipulation of CD45RA+ Tregs, the disclosure of Horneo et al teaches CD4+ CD8− CD25+ CD127lowCD45RA+ Tregs having an enhanced immunosuppression capability and that can serve as potential therapeutics (Pages 304, 307-309). See obviousness rationale in the discussion of instant claim 46 below.
Maus et al further disclose that the engineered Tregs can be administered to a patient in need thereof, including those suffering from an autoimmune condition or allograft rejection (Paragraphs [0012]-[0021], [0059]-[0065], [0150], [0215]-[0220]).
Maus et al do not disclose that the naïve Tregs having a phenotype of CD4+ CD8− CD25++ CD127low CD45RA+ are engineered to express an exogenous FoxP3 polypeptide, as required by instant claim 28.
However, it would have been prima facie obvious to have modified the method of Maus et al such that engineered naïve Tregs comprised the CAR 28ζ FoxP3 CAR construct. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to assess the cytolytic activity of all the anti-CD19 CAR constructs in the naïve Tregs, and would have had a reasonable expectation of success based on the experimental protocols outlined in Maus et al regarding the sorting and engineering of naïve Tregs (Paragraphs [0069], [0207], [0314]-[0315], [0369]). See MPEP § 2143(I)(G).
Consequently, Maus et al render obvious a method of treating an autoimmune disease (claim 30), wherein a pharmaceutical composition comprising a naïve Treg having a phenotype of CD4+ CD8− CD25++ CD127low CD45RA+ that is engineered to express a CAR 28ζ FoxP3 construct (claim 33) is administered to a subject in need thereof. As the naïve Treg cells are successively isolated from a starting population of PBMCs via FACS (claim 34) and the CAR 28ζ FoxP3 construct comprises an exogenous FoxP3 polypeptide, this therefore renders obvious the method of instant claim 28.
Regarding claim 29: Following the discussion of claim 28, Maus et al further disclose that an autoimmune disease is associated with a pathological immune response, and that the treatment of an autoimmune disease involves the suppression of the immune response (Paragraphs [0219], [0224], [0236], [0241]). This therefore reads on the method of the instant claim.
Regarding claim 31: Following the discussion of claim 28, Maus et al further disclose that the autoimmune disease is multiple sclerosis (Paragraphs [0219], [0310]). This therefore reads on the method of the instant claim.
Regarding claim 32: Following the discussion of claim 28, Maus et al further disclose that the exogenous FoxP3 polypeptide is that detailed in NCBI Gene ID: 50943 (Paragraph [0204]). The polypeptide sequence of NCBI Gene ID: 50943 has 100% identity to instant SEQ ID NO: 3, as shown in the sequence alignment at the end of the document (NCBI, forkhead box protein P3 isoform a [Homo sapiens]). This therefore reads on the method of the instant claim.
Regarding claim 41: Maus et al disclose engineered regulatory T cells (Tregs), wherein the Tregs are engineered to promote or increase their immunosuppressive activity (Abstract; Paragraphs [0058], [0184], [0204]).
As such, Maus et al disclose that the engineered Tregs express an exogenous FoxP3 polypeptide or an exogenous nucleic acid encoding the FoxP3 polypeptide (Paragraphs [0039], [0043], [0200], [0204], [0315]). Maus et al further disclose that the engineered Treg cells can also comprise a nucleic acid encoding a chimeric antigen receptor (CAR) polypeptide, wherein a CAR 28ζ FoxP3 construct comprises an anti-CD19 CAR and a FoxP3 transgene – oriented 5’ to 3’, respectively – within a single lentiviral backbone (Paragraphs [0069], [0093], [0205]-[0209], [0315], [0359]; Figures 3, 23A).
Maus et al further disclose that the purified Tregs can be further sorted based on the positive expression of CD45RA (Paragraphs [0132], [0369]; Figure 35F). It is of note that, in the event that the effective filing date of Maus et al does not cover the manipulation of CD45RA+ Tregs, the disclosure of Horneo et al teaches CD4+ CD8− CD25+ CD127lowCD45RA+ Tregs having an enhanced immunosuppression capability and that can serve as potential therapeutics (Pages 304, 307-309). See obviousness rationale in the discussion of instant claim 46 below.
Maus et al do not disclose that the naïve Tregs are transduced with a lentiviral vector comprising the FoxP3 transgene 5’ to the CAR, as required by instant claim 41.
However, it would have been prima facie obvious to have modified the engineered Treg of Maus et al such that the Tregs are engineered with a lentiviral construct comprising the FoxP3 transgene 5’ to the CAR. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to rearrange the lentiviral construct such that the FoxP3 polypeptide is 5’ to the anti-CD19 CAR, as it would have ensured that the CAR expression only occurs – or is induced – by the expression of FoxP3 (Paragraph [0208]), and would have had a reasonable expectation of success based on the experimental protocols outlined in Maus et al regarding the engineering of Tregs (Paragraphs [0069], [0207], [0314]-[0315], [0369]). See MPEP § 2143(I)(G).
Consequently, Maus et al render obvious naïve Tregs that are engineered to express a lentiviral construct respectively comprising from 5’ to 3’ a FoxP3 transgene and an anti-CD19 CAR. As the engineered naïve Tregs have an expression profile of CD4+ CD8− CD25++ CD127low CD45RA+, this therefore renders obvious the engineered CD4+CD25+CD127lowCD45RA+ Treg of the instant claim.
Regarding claim 42: Following the discussion of claim 41, Maus et al further disclose that the exogenous FoxP3 polypeptide is that detailed in NCBI Gene ID: 50943 (Paragraph [0204]). The polypeptide sequence of NCBI Gene ID: 50943 has 100% identity to instant SEQ ID NO: 3, as shown in the sequence alignment at the end of the document (NCBI, forkhead box protein P3 isoform a [Homo sapiens]). This therefore reads on the method of the instant claim.
Regarding claim 43: Following the discussion of claim 41, Maus et al further disclose that the FoxP3 transgene and anti-CD19 CAR are separated by a T2A self-cleaving sequence (Paragraphs [0069], [0315], [0359]-[0360]; Figure 3). This therefore reads on the method of the instant claim.
Regarding claim 44: Following the discussion of claim 41, Maus et al further disclose a pharmaceutical composition comprising the engineered Tregs (Paragraphs [0058]-[0059], [0284]-[0285]). This therefore renders obvious the pharmaceutical composition of the instant claim for the same reasons as discussed in the rejection of claim 41.
Regarding claim 46: Following the discussion of claim 45 above, Maus et al further disclose that the Tregs can be further sorted based on the positive expression of CD45RA (Paragraphs [0132], [0369]; Figure 35F).
It is of note that, in the event that the effective filing date of Maus et al does not cover the manipulation of CD45RA+ Tregs, the disclosure of Horneo et al teaches CD4+ CD8− CD25+ CD127lowCD45RA+ Tregs having an enhanced immunosuppression capability and that can serve as potential therapeutics (Pages 304, 307-309).
Therefore, it would have been prima facie obvious to have modified the method of Maus et al such that the engineered Tregs are naïve Tregs having an expression profile of CD4+ CD8− CD25+ CD127lowCD45RA+, as detailed in Horneo et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to engineer naïve Tregs, as they maintain a high degree of suppressive function and improve therapy overall (Horneo et al: Page 309), and would have had a reasonable expectation of success based on the experimental protocols outlined in Maus et al regarding the sorting and engineering of CD4+ CD8− CD25+ CD127low Tregs (Paragraphs [0069], [0207], [0314]-[0315], [0369]).
Consequently, Maus et al as modified by Horneo et al render obvious a treatment method wherein the engineered Tregs have an expression profile of CD4+ CD8− CD25++ CD127low CD45RA+. This therefore renders obvious the method of the instant claim.
Regarding claim 47: Following the discussion of claim 46, Maus et al further disclose that the autoimmune disease is multiple sclerosis (Paragraphs [0219], [0310]). This therefore reads on the method of the instant claim.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 28-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-7, 9-11, 13, 15, 19-21, and 23 of copending Application No. 18/859911 in view of Horneo et al (Transplantation, 2016, of record on IDS filed 07 January 2026) and Maus et al (US 2020/0330515 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render 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 19 is directed to a method of prevention and/or treatment of a disease comprising administering to a subject an engineered Treg according to claim 15 or a pharmaceutical composition comprising said engineered Treg.
Copending claim 15 is directed to an engineered Treg obtainable or obtained by the method of claim 1.
Copending claim 1 is directed to a method for maintaining the ability of a regulatory T cell (Treg) to suppress immune responses under proinflammatory conditions comprising introducing a polynucleotide encoding a FOXP3 polypeptide into the Treg.
Copending claim 9 further limits the method of copending claim 1, wherein the method comprises (a) isolating a Treg from a cell population; and (b) increasing FOXP3 expression in the Treg. Copending claim 13 further limits the method of copending claim 9, wherein the Treg is isolated by selecting for CD4+CD25+CD127- and/or CD4+CD25+CD1271ow cells.
Copending claim 5 further limits the method of copending claim 1, which further comprises introducing a polynucleotide encoding an exogenous T cell receptor (TCR) or a polynucleotide encoding a chimeric antigen receptor (CAR) into the Treg. Copending claim 6 further limits the method of copending claim 5, wherein the polynucleotide encoding a FOXP3 polypeptide and the polynucleotide encoding the exogenous TCR or the CAR are provided by i) a single expression vector; and/or (ii) a vector comprising a nucleic acid with an orientation of: 5' FOXP3 - TCR/CAR3'.
The copending application fails to teach that the Tregs have an expression profile of CD4+CD25+CD127-/lowCD45RA+, as required by instant claims 28 and 41.
Horneo et al, however, disclose CD4+ CD8− CD25+ CD127lowCD45RA+ Tregs having an enhanced immunosuppression capability and that can serve as potential therapeutics (Pages 304, 307-309).
Therefore, it would have been prima facie obvious to have modified the treatment method of the copending application such that the engineered Tregs are naïve Tregs having an expression profile of CD4+ CD8− CD25+ CD127lowCD45RA+, as detailed in Horneo et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to engineer naïve Tregs, as they maintain a high degree of suppressive function and improve therapy overall (Horneo et al: Page 309), and would have had a reasonable expectation of success based on the experimental protocols outlined in the copending application regarding the sorting and engineering of CD4+ CD8− CD25+ CD127low Tregs.
Consequently, copending claims 1, 9, 13, 15, and 19 in view of Horneo et al render obvious the method of instant claim 28. Copending claims 1, 5-6, 15, and 19 in view of Horneo et al render obvious the engineered Treg of instant claim 41, pharmaceutical composition of instant claim 44, and the method of instant claims 45-46.
With that, instant claims 29-34 and 42-43 are known from the copending application or prior art and can be further incorporated into the method rendered obvious by copending claims 1, 9, 13, 15, and 19 in view of Horneo et al:
Copending claims 3, 5, 7, 20-21, and 23 teach the limitations recited in instant claims 30-34, 42, and 47.
Maus et al teach the limitations recited in instant claims 29 and 43.
Copending claim 1 is directed to a method for maintaining the ability of a regulatory T cell (Treg) to suppress immune responses under proinflammatory conditions comprising introducing a polynucleotide encoding a FOXP3 polypeptide into the Treg.
Copending claim 5 further limits the method of copending claim 1, which further comprises introducing a polynucleotide encoding an exogenous T cell receptor (TCR) or a polynucleotide encoding a chimeric antigen receptor (CAR) into the Treg. Copending claim 6 further limits the method of copending claim 5, wherein the polynucleotide encoding a FOXP3 polypeptide and the polynucleotide encoding the exogenous TCR or the CAR are provided by i) a single expression vector; and/or (ii) a vector comprising a nucleic acid with an orientation of: 5' FOXP3 - TCR/CAR3'.
Copending claim 15 is directed to an engineered Treg obtainable or obtained by the method of claim 1.
This therefore renders obvious the method of instant claim 35 and engineered Treg of instant claim 40, as the copending method is a variant of instant claim 35.
With that, instant claims 36-39 are known from the copending application or prior art and can be further incorporated into the method rendered obvious by copending claims 1 and 5-6:
Copending claims 3 and 9-11 teach the limitations recited in instant claims 36-38.
Maus et al teach the limitations recited in instant claim 39.
This is a provisional nonstatutory double patenting rejection.
Claims 28-34 and 41-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4-9 of U.S. Patent No. 12077774 B2 in view of Maus et al (US 2020/0330515 A1). It is of note that the instant application is a CONTINUATION of US Patent No. 12077774 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims render obvious the instant claims. More specifically, the patent claims are 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, 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 pharmaceutical composition comprising an engineered regulatory T cell (Treg) with an enhanced ability to suppress immune responses obtained by a process comprising: a) isolating a CD4+CD25+CD127−/lowCD45RA+ Treg from a cell population; and b) introducing a polynucleotide encoding a FOXP3 polypeptide into the isolated CD4+CD25+CD127−/lowCD45RA+ Treg to enhance the ability of the Treg to suppress immune responses.
Although the patent claims fail to teach a method of treating or preventing a disease using the pharmaceutical composition, it has been held that a claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86, and Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F. 3d 1381, 1387 (CAFC 2010). See MPEP 804(II)(B)(1).
Therefore, since the product within patent claim 1 and instant claim 28 are identical, patent claim 1 renders obvious the method of instant claim 28.
As aforementioned, patent claim 1 is directed to a pharmaceutical composition comprising an engineered regulatory T cell (Treg) with an enhanced ability to suppress immune responses obtained by a process comprising: a) isolating a CD4+CD25+CD127−/lowCD45RA+ Treg from a cell population; and b) introducing a polynucleotide encoding a FOXP3 polypeptide into the isolated CD4+CD25+CD127−/lowCD45RA+ Treg to enhance the ability of the Treg to suppress immune responses.
Patent claim 4 further limits the pharmaceutical composition of patent claim 1, wherein the process further comprises introducing a polynucleotide encoding an exogenous T cell receptor (TCR) or a polynucleotide encoding a chimeric antigen receptor (CAR) into the Treg. Patent claim 5 further limits the pharmaceutical composition of patent claim 4, wherein the polynucleotide encoding a FOXP3 polypeptide and the polynucleotide encoding the exogenous TCR or the CAR are provided by a single expression vector.
The patent claims fail to teach that the FOXP3 polypeptide and exogenous TCR or CAR are comprised within the single expression vector in the 5’ to 3’ orientation of the FOXP3 polypeptide and exogenous TCR/CAR.
Maus et al, however, disclose a CAR 28ζ FoxP3 construct comprising an anti-CD19 CAR and a FoxP3 transgene – oriented 5’ to 3’, respectively – within a single lentiviral backbone (Paragraphs [0069], [0093], [0205]-[0209], [0315], [0359]; Figures 3, 23A)
However, it would have been prima facie obvious to have modified the engineered Treg of patent claims 1 and 4-5 such that the Tregs are engineered with a lentiviral construct comprising the FoxP3 transgene 5’ to the CAR. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to rearrange the lentiviral construct such that the FoxP3 polypeptide is 5’ to the anti-CD19 CAR, as it would have ensured that the CAR expression only occurs – or is induced – by the expression of FoxP3 (Maus et al: Paragraph [0208]), and would have had a reasonable expectation of success based on the experimental protocols outlined in Maus et al regarding the engineering of Tregs (Paragraphs [0069], [0207], [0314]-[0315], [0369]). See MPEP § 2143(I)(G).
Consequently, patent claims 1 and 4-5 in view of Maus et al render obvious a pharmaceutical composition comprising a CD4+CD25+CD127−/lowCD45RA+ Treg that is engineered to comprise an expression vector respectively comprising from 5’ to 3’ a FoxP3 transgene and an anti-CD19 CAR. This therefore renders obvious the pharmaceutical composition of instant claim 44 and engineered CD4+CD25+CD127−/lowCD45RA+ Treg of instant claim 41.
With that, instant claims 29-34 and 42-43 are known from the patent or prior art and can be further incorporated into the method rendered obvious by patent claim 1 or patent claims 1 and 4-5 in view of Maus et al:
Patent claims 2-9 teach the limitations recited in instant claims 32-34 and 42.
Maus et al teach the limitations recited in instant claims 29-31 and 43.
Examiner’s Comment
The pharmaceutical composition claimed within parent application 17/048239, now US
Patent 12,077,774 B2, was found allowable due to considerations presented within the Declaration under 37 CFR 1.132 filed 14 February 2024 by co-Inventor Dr. Jenny McGovern. The Examiner would like
to note that declarations are not imported from the parent application, and must be refiled within the
instant application to be considered. See MPEP § 716.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can
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/ALYSSA G WESTON/Examiner, Art Unit 1633
Sequence Alignment
Query Match 100.0%; Score 2312; DB 1; Length 431; Best Local Similarity 100.0%;
Qy 1 MPNPRPGKPSAPSLALGPSPGASPSWRAAPKASDLLGARGPGGTFQGRDLRGGAHASSSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPNPRPGKPSAPSLALGPSPGASPSWRAAPKASDLLGARGPGGTFQGRDLRGGAHASSSS 60
Qy 61 LNPMPPSQLQLPTLPLVMVAPSGARLGPLPHLQALLQDRPHFMHQLSTVDAHARTPVLQV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LNPMPPSQLQLPTLPLVMVAPSGARLGPLPHLQALLQDRPHFMHQLSTVDAHARTPVLQV 120
Qy 121 HPLESPAMISLTPPTTATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPNPSAPRKD 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 HPLESPAMISLTPPTTATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPNPSAPRKD 180
Qy 181 STLSAVPQSSYPLLANGVCKWPGCEKVFEEPEDFLKHCQADHLLDEKGRAQCLLQREMVQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 STLSAVPQSSYPLLANGVCKWPGCEKVFEEPEDFLKHCQADHLLDEKGRAQCLLQREMVQ 240
Qy 241 SLEQQLVLEKEKLSAMQAHLAGKMALTKASSVASSDKGSCCIVAAGSQGPVVPAWSGPRE 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SLEQQLVLEKEKLSAMQAHLAGKMALTKASSVASSDKGSCCIVAAGSQGPVVPAWSGPRE 300
Qy 301 APDSLFAVRRHLWGSHGNSTFPEFLHNMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 APDSLFAVRRHLWGSHGNSTFPEFLHNMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTL 360
Qy 361 NEIYHWFTRMFAFFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDELEFRKKRSQR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NEIYHWFTRMFAFFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDELEFRKKRSQR 420
Qy 421 PSRCSNPTPGP 431 (SEQ ID NO: 3)
|||||||||||
Db 421 PSRCSNPTPGP 431 (GENE ID: 50943)
Query Match 100.0%; Score 2312; DB 1; Length 431; Best Local Similarity 100.0%;
Qy 1 MPNPRPGKPSAPSLALGPSPGASPSWRAAPKASDLLGARGPGGTFQGRDLRGGAHASSSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPNPRPGKPSAPSLALGPSPGASPSWRAAPKASDLLGARGPGGTFQGRDLRGGAHASSSS 60
Qy 61 LNPMPPSQLQLPTLPLVMVAPSGARLGPLPHLQALLQDRPHFMHQLSTVDAHARTPVLQV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LNPMPPSQLQLPTLPLVMVAPSGARLGPLPHLQALLQDRPHFMHQLSTVDAHARTPVLQV 120
Qy 121 HPLESPAMISLTPPTTATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPNPSAPRKD 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 HPLESPAMISLTPPTTATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPNPSAPRKD 180
Qy 181 STLSAVPQSSYPLLANGVCKWPGCEKVFEEPEDFLKHCQADHLLDEKGRAQCLLQREMVQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 STLSAVPQSSYPLLANGVCKWPGCEKVFEEPEDFLKHCQADHLLDEKGRAQCLLQREMVQ 240
Qy 241 SLEQQLVLEKEKLSAMQAHLAGKMALTKASSVASSDKGSCCIVAAGSQGPVVPAWSGPRE 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SLEQQLVLEKEKLSAMQAHLAGKMALTKASSVASSDKGSCCIVAAGSQGPVVPAWSGPRE 300
Qy 301 APDSLFAVRRHLWGSHGNSTFPEFLHNMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 APDSLFAVRRHLWGSHGNSTFPEFLHNMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTL 360
Qy 361 NEIYHWFTRMFAFFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDELEFRKKRSQR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NEIYHWFTRMFAFFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDELEFRKKRSQR 420
Qy 421 PSRCSNPTPGP 431 (INSTANT SEQ ID NO: 3)
|||||||||||
Db 421 PSRCSNPTPGP 431 (18/859911 SEQ ID NO: 3)
Query Match 100.0%; Score 2312; DB 1; Length 431; Best Local Similarity 100.0%;
Qy 1 MPNPRPGKPSAPSLALGPSPGASPSWRAAPKASDLLGARGPGGTFQGRDLRGGAHASSSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPNPRPGKPSAPSLALGPSPGASPSWRAAPKASDLLGARGPGGTFQGRDLRGGAHASSSS 60
Qy 61 LNPMPPSQLQLPTLPLVMVAPSGARLGPLPHLQALLQDRPHFMHQLSTVDAHARTPVLQV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LNPMPPSQLQLPTLPLVMVAPSGARLGPLPHLQALLQDRPHFMHQLSTVDAHARTPVLQV 120
Qy 121 HPLESPAMISLTPPTTATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPNPSAPRKD 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 HPLESPAMISLTPPTTATGVFSLKARPGLPPGINVASLEWVSREPALLCTFPNPSAPRKD 180
Qy 181 STLSAVPQSSYPLLANGVCKWPGCEKVFEEPEDFLKHCQADHLLDEKGRAQCLLQREMVQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 STLSAVPQSSYPLLANGVCKWPGCEKVFEEPEDFLKHCQADHLLDEKGRAQCLLQREMVQ 240
Qy 241 SLEQQLVLEKEKLSAMQAHLAGKMALTKASSVASSDKGSCCIVAAGSQGPVVPAWSGPRE 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SLEQQLVLEKEKLSAMQAHLAGKMALTKASSVASSDKGSCCIVAAGSQGPVVPAWSGPRE 300
Qy 301 APDSLFAVRRHLWGSHGNSTFPEFLHNMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 APDSLFAVRRHLWGSHGNSTFPEFLHNMDYFKFHNMRPPFTYATLIRWAILEAPEKQRTL 360
Qy 361 NEIYHWFTRMFAFFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDELEFRKKRSQR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NEIYHWFTRMFAFFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDELEFRKKRSQR 420
Qy 421 PSRCSNPTPGP 431 (INSTANT SEQ ID NO: 3)
|||||||||||
Db 421 PSRCSNPTPGP 431 (US 12077774 B2 SEQ ID NO: 3)
Prosecution Insights