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. 16/981086, filed 15 September 2020 (now US Patent 12,037,362 B2), which is a national stage entry under 35 USC 371 of PCT/EP2019/058560, filed 04 April 2019. Acknowledgement is made of Applicant’s claim for foreign priority under 35 USC 119(a)-(d) to Application No. EP18305399.0, filed 05 April 2018. Receipt is acknowledged of the certified copies of papers required by 37 CFR 1.55, which are filed in parent Application No. 16/981086, filed 15 September 2020.
Therefore, the effective filing date of the instant invention is 05 April 2018.
Status of the Claims
Applicant’s preliminary amendments filed 18 August 2024 has been entered. Claims 19-32 are pending. Claims 1-18 have been cancelled without prejudice or disclaimer, while and claims 19-32 have been newly added. Therefore, prosecution on the merits commences for claims 19-32.
Claim Objections
Claims 19, 26, and 30 are objected to because of the following informalities:
Regarding claim 19: The instant claim is objected to for utilizing bullet points within the claim
language. See MPEP § 608.01(m).
Appropriate correction is required.
Regarding claim 26: The instant claim is objected to for reciting “hybrid recombinant AAV capsid protein” instead of “ hybrid AAV capsid protein”, which is the term consistently utilized throughout the claim language.
Appropriate correction is required.
Regarding claim 30: The instant claim is objected to for reciting “a neuromuscular genetic disorders” instead of “a neuromuscular genetic disorder[[s]]”.
Appropriate correction is required.
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.
Claim 29 is 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 treatment of neuromuscular genetic disorders and diseases affecting muscle tissues, does not reasonably provide enablement for the 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 29 is directed to a method of treating a disease by gene therapy, comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 28.
The pharmaceutical composition of claim 28 comprises a therapeutically effective amount of AAV vector particles according to claim 26.
The AAV vector particles of claim 26 package a gene of interest and comprise one or more of the recombinant hybrid AAV capsid protein according to claim 19.
The recombinant hybrid AAV capsid protein of claim 19 is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins, comprising a N-terminal sequence joined to a C-terminal sequence, wherein: the N-terminal sequence consists of the sequence from positions 1 to 448 of AAV9 capsid of SEQ ID NO: 1 and the sequence from positions 450 to 587 of AAVrh74 capsid of SEQ ID NO:2; and the C-terminal sequence consists of the sequence from positions 594 to 611 of AAVrh74 capsid of SEQ ID NO: 2 and the sequence from positions 610 to the end of AAV9 capsid of SEQ ID NO: 1; wherein said recombinant hybrid AAV capsid protein has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins
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 method allows for the treatment of any disease or disorder in any subject using a pharmaceutical composition comprising AAV vector particles that comprise, in part, any gene of interest. 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 treatment of all diseases. Instead, the instant disclosure provides exemplary target genes for the treatment of neuromuscular genetic disorders and diseases affecting muscle tissues – particularly, dystrophinopathies, Limb-girdle muscular dystrophies, Facio-scapulo-humeral dystrophies, titinopathies, cancer, and auto-immune diseases. See, for example, Pages 14-30 of the instant Specification filed 06 June 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 for the systemic administration of a peptide-modified hybrid AAV9-rh74 serotype vector to B6Albino mice to assess the biodistribution of the vector. See Example 3, which correlates to Pages 35-36 of the instant Specification. Therefore, Applicant has not provided sufficient evidence of the treatment of any disease or disorder in any subject using a pharmaceutical composition comprising AAV vector particles that comprise, in part, any gene of interest.
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 recombinant hybrid AAV vector particles for the treatment of a broad range of diseases given the unpredictable tropism. More specifically, the disclosure of Choi et al (Curr Gene Ther, 2005) teaches that even a slight alteration in viral capsid structure in chimeric capsid proteins can affect receptor binding and potentially downstream events, thus reducing transduction efficiency (Page 11). Choi et al further disclose that the transduction efficiency and tropism of mutant serotypes can differ between in vivo and in vitro studies, and for particular cell types (Pages 13-14).
Therefore, the full scope of the claim is thus not enabled in regards to the treatment of any disease or disorder in any subject using pharmaceutical composition comprising AAV vector particles that comprise, in part, any gene of interest, since at best it would require undue trial and error experimentation.
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 30-31 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 recites the limitation “which targets a gene responsible for a neuromuscular genetic disorder selected from the group comprising: Dystrophinopathies, Limb-girdle muscular dystrophies, Facio-scapulo-humeral dystrophies and titinopathies” (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 “comprising” indicates that the Markush group is open, thus rendering the metes and bounds of the claim indefinite.
Appropriate correction is required.
Regarding claim 31: The instant claim recites the limitation "the target gene" in Line 1. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of a “target gene” within the instant claim or parent claims 19, 26, and 28-29. See MPEP § 2173.05(e). It is of note that the “target gene” is not necessarily the “gene of interest” in parent claim 26.
Appropriate correction is required.
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 19-20 and 22-32 are rejected under 35 U.S.C. 103 as being unpatentable over Colosi et al (WO 2018/022608 A2, of record on IDS filed 06 June 2024) in view of High et al (WO 2015/013313 A2, of record on IDS filed 06 June 2024) and Asokan et al (US 2015/0152142 A1).
Colosi et al, High et al, and Asokan et al are each considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Colosi et al has a publication date of 01 February 2018.
Regarding claims 19-20: Colosi et al disclose novel adeno-associated virus (AAV) capsid proteins, AAV particles comprising a novel capsid protein, polynucleotides encoding these capsid proteins, and AAV vectors expressing these capsid proteins (Abstract; Paragraph [0002]).
As such, Colosi et al disclose recombinant chimeric AAV capsid proteins, wherein an AAV capsid protein sequence of the invention (e.g., a fragment of a VP1 capsid protein, or a GH loop region) can be used in combination with heterologous sequences which may be obtained from another known or novel AAV serotype (Paragraphs [0006]-[0007], [0009], [0018]-[0024], [0026]-[0029], [0047], [0057], [0073], [0077]-[0080], [00208]-[00209]).
In certain embodiments, Colosi et al disclose that the recombinant chimeric AAV capsid proteins have a GH loop region sequence derived from a donor capsid sequence that differs from the recipient capsid sequence (Paragraphs [0009], [0014], [0018], [0022]-[0025], [0047], [0080]). Colosi et al further disclose the VP1 sequence of AAV9 in SEQ ID NO: 10 – which has 100% identity to instant SEQ ID NO: 1 (see sequence alignment at end of document) – with corresponding GH loop sequence ranging from amino acids 448-602 (Paragraphs [0028], [0078], [00171]; Table 2). Colosi et al further disclose the VP1 sequence of AAVrh10 in SEQ ID NO: 12 – which has 99% identity to instant SEQ ID NO: 2 (see sequence alignment at end of document) – with corresponding GH loop sequence ranging from amino acid 449-603 (Paragraphs [0028], [0078], [00171]; Table 2). It is of note that Colosi et al disclose that the location of the N-terminal and/or C-terminal ends of the GH loop regions may vary by from up to 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids or 5 amino acids from the amino acid locations of those regions as they are explicitly described, particularly in Table 2 (Paragraph [0023).
Colosi et al further disclose another recombinant AAV structure in SEQ ID NO: 157 that comprises an AAV9 backbone with a substituted AAVrh10 variable region and has 98.9% identity to instant SEQ ID NO: 3 (Paragraph [00209]; Table 3). See sequence alignment at end of document.
Colosi et al do not disclose a recombinant chimeric AAV structure that has an AAV9 backbone with a variable region ranging from amino acid positions 449 to 609 that is substituted with an AAVrh74 variable region ranging from amino acid positions 450 to 611, wherein the recombinant chimeric AAV structure is split into a N-terminal sequence of positions 1 to 448 of AAV9 and positions 450-587 of AAVrh74 joined to a C-terminal sequence of positions 594-611 of AAVrh74 and 610 to 736 of AAV9, as required by instant claim 19.
High et al, however, disclose AAVrh74 and related AAV vectors, and AAVrh74 and related AAV vector mediated gene transfer methods and uses (Abstract).
As such, High et al disclose that the recombinant AAV vectors or sequences can include elements from any one serotype, a mixture of serotypes, or hybrids or chimeras of different serotypes (Paragraphs [0034], [0053]). High et al further disclose that a recombinant AAV vector includes a Cap, Rep, and/or ITR sequence derived from AAV9, AAVrh74, or AAVrh10 serotypes, or a mixture, hybrid or chimera of any of the AAV serotypes (Paragraphs [0034], [0053]). It is of note that High et al disclose an AAVrh74 VP1 sequence in SEQ ID NO: 1 that has 100% identity to SEQ ID NO: 2 of the instant disclosure (Paragraph [0037]; Figure 3). See sequence alignment at end of document.
With that, Asokan et al teach that the AAV9 serotype is highly efficient in transducing muscle and liver, and that chimeric AAV vectors comprising AAV9 can decrease the liver transduction (Paragraphs [0005], [0008], [0082]-[0083], [0250]). Asokan et al further disclose recombinant hybrid AAV capsid proteins comprising AAV9 and AAV10 serotypes (Paragraphs [0086], [0214], [0241]).
Therefore, it would have been prima facie obvious to have modified the recombinant chimeric AAV capsid protein of Colosi et al to instead comprise a GH loop sequence of AAVrh74 within the AAV9 backbone, as detailed in High et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize AAVrh74 within the AAV9 backbone due to the broad tropism and reduced seroprevalence of AAVrh74 (High et al: Paragraphs [0006], [0117], and would have had a reasonable expectation of success based on the protocols outlined in Colosi et al (Paragraph [0080]; Table 2) coupled with the fact the amino acid sequence ranging from positions 450 to 611 of the AAVrh10 and AAVrh74 VP1 sequences are identical. See MPEP § 2143(I)(G).
Consequently, Colosi et al as modified by High et al and Asokan et al render obvious a recombinant chimeric AAV capsid protein wherein the GH loop sequence of AAV9 is substituted with the GH loop sequence of AAVrh74, thereby having a reduced liver tropism and maintained muscle tropism (claim 20). Although the GH loop sequences do not directly correspond to the variable regions listed in the instant claim, it would have been within the skillset of the ordinary artisan to adapt the amino acid range since the sequences are merely close, and Colosi et al teach that the N-terminal and/or C-terminal ends of the GH loop regions may vary by up to 5 amino acids. MPEP § 2143(I)(E). As the structure of the recombinant chimeric AAV capsid protein rendered obvious by Colosi et al as modified by High et al and Asokan et al will have the same structure as detailed in the claimed recombinant hybrid AAV capsid protein comprising the defined N-terminal and C-terminal sequences, this therefore renders obvious the recombinant hybrid AAV capsid protein of instant claim 19.
Regarding claim 22: Following the discussion of claim 19, Asokan et al further disclose that positions 575 to 600 in the loop region of an AAV2 capsid protein – or the corresponding amino acid positions in other AAV capsid proteins – can be amended to comprise the sequence QQNAAP, as recited in SEQ ID NO: 26 of Asokan et al (Paragraphs [0082]-[0089], [0207]-[0208], [0214]).
The combination of Colosi et al, High et al, and Asokan et al fail to teach that amino acids at positions 587-592 of the recombinant AAV9/AAVrh47 capsid protein are replaced with the sequence of QQNAAP, as required by instant claim 22.
However, it would have been prima facie obvious to have modified the recombinant chimeric AAV capsid protein of Colosi et al in view of High et al and Asokan et al such that amino acid positions 587-592 of the recombinant AAV9/AAVrh47 capsid protein are replaced by the sequence of QQNAAP, as detailed in Asokan et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to include the sequence, as it reduces the liver tropism of the AAV capsid protein (Asokan et al: Paragraphs [0006], [0008]-[0015]), and would have had a reasonable expectation of success given that Colosi et al define the loop regions of the AAV9 capsid protein and the claimed amino acid range is within the loop range taught by Asokan et al. See MPEP § 2143(I)(G) and MPEP § 2143(I)(E).
Consequently, Colosi et al as modified by High et al and Asokan et al render obvious a recombinant chimeric AAV capsid protein wherein positions 587-592 of the recombinant AAV9/AAVrh47 capsid protein are replaced with the sequence of QQNAAP. As the replacement of those amino acid positions allows for the joining of the remaining N-terminal and C-terminal regions via that sequence, this therefore renders obvious the recombinant hybrid AAV capsid protein of the instant claim.
Regarding claim 23: Following the discussion of claim 19, Colosi et al further disclose that the recombinant chimeric AAV capsid protein is a chimeric VP1 protein (Paragraphs [0007], [0009], [0016]-[0018], [0020]-[0022], [0047], [0057]). This therefore reads on the recombinant hybrid AAV capsid protein of the instant claim.
Regarding claim 24: Following the discussion of claim 19, Colosi et al further disclose a polynucleotide encoding the recombinant chimeric AAV capsid protein (Paragraphs [0002], [0016]-[0017], [0029], [0035], [0057]). This therefore renders obvious the polynucleotide of the instant claim for the same reasons as discussed in the rejection of instant claim 19.
Regarding claim 25: Following the discussion of claim 24, Colosi et al further disclose a plasmid comprising the polynucleotide encoding the recombinant chimeric AAV capsid protein (Paragraphs [0055], [0076], [0079], [00180], [00189]). This therefore renders obvious the recombinant plasmid of the instant claim for the same reasons as discussed in the rejection of instant claim 19.
Regarding claim 26: Following the discussion of claim 19, Colosi et al further disclose AAV vector particles comprising a transgene and the recombinant chimeric AAV capsid protein (Paragraphs [0008], [0009], [0011], [0029], [0035], [0044]-[0046], [0049]-[0050], [0077], [00172]-[00179], [00191]). This therefore renders obvious the AAV vector particle of the instant claim for the same reasons as discussed in the rejection of instant claim 19.
Regarding claim 27: Following the discussion of claim 26, Colosi et al further disclose that the transgene is a therapeutic gene (Paragraphs [0010]-[0012], [0015], [00172]-[00179]). This therefore reads on the AAV vector particle of the instant claim.
Regarding claim 28: Following the discussion of claim 26, Colosi et al further disclose a pharmaceutical composition comprising an effective amount of the AAV vector particles (Paragraphs [0008], [0009], [0011], [0016]-[0017], [0029]). This therefore renders obvious the pharmaceutical composition of the instant claim for the same reasons as discussed in the rejection of instant claim 19.
Regarding claims 29-30 and 32: Following the discussion of claim 28, Colosi et al further disclose a method of treating Duchenne muscular dystrophy (claim 30), wherein the pharmaceutical composition is administered to a subject in need thereof (Paragraphs [0010]-[0012], [00176], [00178]-[00179]). As Duchenne muscular dystrophy is a genetic disease (claim 32) (Paragraph [00179]), this therefore renders obvious the method of instant claim 29 for the same reasons as discussed in the rejection of instant claim 19.
Regarding claim 31: Following the discussion of claim 29, Colosi et al further disclose that the transgene encodes for dystrophin (Paragraphs [0010]-[0012], [0046], [00178]-[00179]). As the DMD target gene inherently encodes for dystrophin, this therefore reads on the method of the instant claim. See Pages 14 and 28 of the instant Specification.
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 19-20 and 22-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12037362 B2 in view of Colosi et al (WO 2018/022608 A2, of record on IDS filed 06 June 2024) and Asokan et al (US 2015/0152142 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims anticipate and/or render obvious the instant claims. More specifically, when applicable, 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 application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 1 is directed to a recombinant adeno-associated virus (AAV) capsid protein, which is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins, wherein:
said recombinant hybrid AAV capsid protein comprises the sequence of SEQ ID NO: 3;
wherein said recombinant hybrid AAV capsid protein has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins, and the muscle tropism of the parent AAV9 and/or AAVrh74 capsid proteins is maintained in the recombinant hybrid AAV capsid protein.
This therefore anticipates the recombinant hybrid AAV capsid protein of instant claims 19-20, as the structure of the patented recombinant chimeric AAV capsid protein will be the same as detailed in the claimed recombinant hybrid AAV capsid protein comprising the defined N-terminal and C-terminal sequences. See sequence alignment below.
With that, instant claims 22-32 are known from the patent or prior art and can be further incorporated into the recombinant hybrid AAV capsid protein anticipated by patent claim 1:
Patent claims 2-7 teach the limitations recited in instant claims 23 and 26-31.
Asokan et al teach the limitations recited in instant claim 22.
Colosi et al teach the limitations recited in instant claims 24-25 and 32.
Allowable Subject Matter
Claim 21 is objected to as being dependent upon a rejected base claim, but would be allowable
if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art regarding instant claim 21 is Bremel et al (US 2013/0330335 A1), which disclose the sequences of SEQ ID NOs: 431299 and 449790, which have 100% sequence identity to instant SEQ ID NOs: 35-36, respectively. However, the sequences of Bremel et al are directed to B-cell and T-cell epitopes, and cannot be rendered obvious with the cited prior art.
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 normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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/ALYSSA G WESTON/Examiner, Art Unit 1633
Sequence Alignments
INSTANT SEQ ID NO: 1 (Qy) vs Colosi et al SEQ ID NO: 10 (Db)
Query Match 100.0%; Length 736; Matches 736; Mismatches 0; Gaps 0
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
Qy 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
Qy 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
Qy 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
Qy 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480
Qy 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540
Qy 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600
Qy 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660
Qy 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720
Qy 721 YSEPRPIGTRYLTRNL 736
||||||||||||||||
Db 721 YSEPRPIGTRYLTRNL 736
INSTANT SEQ ID NO: 2 (Qy) vs Colosi et al SEQ ID NO: 12 (Db)
Query Match 99.0%; Length 738; Matches 730; Conservative 4; Mismatches 4; Indels 0; Gaps 0;
Qy 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDNGRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||||||||||||||||||||:|||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLQAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
|||||||||||||||||||||||:||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPLGLVESPVKTAPGKKRPVEPSPQRSPDSSTGIGKKGQQPAKKRLNFGQTGDS 180
||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRVLEPLGLVEEGAKTAPGKKRPVEPSPQRSPDSSTGIGKKGQQPAKKRLNFGQTGDS 180
Qy 181 ESVPDPQPIGEPPAGPSGLGSGTMAAGGGAPMADNNEGADGVGSSSGNWHCDSTWLGDRV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ESVPDPQPIGEPPAGPSGLGSGTMAAGGGAPMADNNEGADGVGSSSGNWHCDSTWLGDRV 240
Qy 241 ITTSTRTWALPTYNNHLYKQISNGTSGGSTNDNTYFGYSTPWGYFDFNRFHCHFSPRDWQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ITTSTRTWALPTYNNHLYKQISNGTSGGSTNDNTYFGYSTPWGYFDFNRFHCHFSPRDWQ 300
Qy 301 RLINNNWGFRPKRLNFKLFNIQVKEVTQNEGTKTIANNLTSTIQVFTDSEYQLPYVLGSA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RLINNNWGFRPKRLNFKLFNIQVKEVTQNEGTKTIANNLTSTIQVFTDSEYQLPYVLGSA 360
Qy 361 HQGCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFEFSYNFED 420
|||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||
Db 361 HQGCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFEFSYQFED 420
Qy 421 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNW 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNW 480
Qy 481 LPGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSS 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 LPGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSS 540
Qy 541 GVLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GVLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNS 600
Qy 601 QGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGLKHPPPQILIKNTPVPADP 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 QGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGLKHPPPQILIKNTPVPADP 660
Qy 661 PTTFNQAKLASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSTNVDFAVNTE 720
||||:||||||||||||||||||||||||||||||||||||||||||||||||||||||:
Db 661 PTTFSQAKLASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSTNVDFAVNTD 720
Qy 721 GTYSEPRPIGTRYLTRNL 738
||||||||||||||||||
Db 721 GTYSEPRPIGTRYLTRNL 738
INSTANT SEQ ID NO: 3(Qy) vs Colosi et al SEQ ID NO: 157 (Db)
Query Match 98.9%; Length 737; Matches 728; Conservative 4; Mismatches 5; Indels 0; Gaps 0;
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
Qy 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
|||||||||||||||||||||| |||||:|||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISNGTSGGSTNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
Qy 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
|||||||||||||||||||||||||| | | |||||||||||||||||||||||||||||
Db 301 LINNNWGFRPKRLNFKLFNIQVKEVTQNEGTKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
Qy 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
|||||||||||||||||||||||:||||||||||||||||||||||||||||||||||||
Db 361 EGCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
Qy 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNWL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNWL 480
Qy 481 PGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSSG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSSG 540
Qy 541 VLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNSQ 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 VLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNSQ 600
Qy 601 GALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPP 660
|||||||||:||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GALPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPP 660
Qy 661 TAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEG 720
||||||||||||||||||||||||||||||||||||||||||||||||| ||:|||||||
Db 661 TAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSTNVDFAVNTEG 720
Qy 721 VYSEPRPIGTRYLTRNL 737
|||||||||||||||||
Db 721 VYSEPRPIGTRYLTRNL 737
INSTANT SEQ ID NO: 2 (Qy) vs High et al SEQ ID NO: 1 (Db)
Query Match 100.0%; Length 738; Matches 738; Mismatches 0; Gaps 0
Qy 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDNGRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDNGRGLVLPGYKYLGPFNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLQAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLQAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPLGLVESPVKTAPGKKRPVEPSPQRSPDSSTGIGKKGQQPAKKRLNFGQTGDS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRVLEPLGLVESPVKTAPGKKRPVEPSPQRSPDSSTGIGKKGQQPAKKRLNFGQTGDS 180
Qy 181 ESVPDPQPIGEPPAGPSGLGSGTMAAGGGAPMADNNEGADGVGSSSGNWHCDSTWLGDRV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ESVPDPQPIGEPPAGPSGLGSGTMAAGGGAPMADNNEGADGVGSSSGNWHCDSTWLGDRV 240
Qy 241 ITTSTRTWALPTYNNHLYKQISNGTSGGSTNDNTYFGYSTPWGYFDFNRFHCHFSPRDWQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ITTSTRTWALPTYNNHLYKQISNGTSGGSTNDNTYFGYSTPWGYFDFNRFHCHFSPRDWQ 300
Qy 301 RLINNNWGFRPKRLNFKLFNIQVKEVTQNEGTKTIANNLTSTIQVFTDSEYQLPYVLGSA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RLINNNWGFRPKRLNFKLFNIQVKEVTQNEGTKTIANNLTSTIQVFTDSEYQLPYVLGSA 360
Qy 361 HQGCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFEFSYNFED 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 HQGCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFEFSYNFED 420
Qy 421 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNW 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNW 480
Qy 481 LPGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSS 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 LPGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSS 540
Qy 541 GVLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GVLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNS 600
Qy 601 QGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGLKHPPPQILIKNTPVPADP 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 QGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGLKHPPPQILIKNTPVPADP 660
Qy 661 PTTFNQAKLASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSTNVDFAVNTE 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 PTTFNQAKLASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSTNVDFAVNTE 720
Qy 721 GTYSEPRPIGTRYLTRNL 738
||||||||||||||||||
Db 721 GTYSEPRPIGTRYLTRNL 738
INSTANT SEQ ID NO: 1 (Qy) vs Patent SEQ ID NO: 3 (Db)
Query Match 91.7%; Length 737; Matches 676; Conservative 21; Mismatches 39; Indels 1; Gaps 1;
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
Qy 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
Qy 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
Qy 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
Qy 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKT-INGSGQNQQTLKFSVAGPSNMAVQGRNYI 479
||||||||||||||||||||||||||||:| | | | || |||:||: | :|::
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNWL 480
Qy 480 PGPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSG 539
||| |||||||||::||||| ||| ||: : ||||:||:||| |||:||: |:|||| ||
Db 481 PGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSSG 540
Qy 540 SLIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQ 599
|:||||| |:|||| ||:|:||||||||||||| || || | | | | | :|
Db 541 VLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNSQ 600
Qy 600 GILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPP 659
| |||||||:||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPP 660
Qy 660 TAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEG 719
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 TAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEG 720
Qy 720 VYSEPRPIGTRYLTRNL 736
|||||||||||||||||
Db 721 VYSEPRPIGTRYLTRNL 737
INSTANT SEQ ID NO: 2 (Qy) vs Patent SEQ ID NO: 3 (Db)
Query Match 94.1%; Length 737; Matches 692; Conservative 19; Mismatches 26; Indels 1; Gaps 1;
Qy 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDNGRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||| ||||||:|||||| ||| ||||||||||||| ||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLQAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
|||||||||||||||||||||||:|||||||:||||||||||||:|||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPLGLVESPVKTAPGKKRPVEPSPQRSPDSSTGIGKKGQQPAKKRLNFGQTGDS 180
||||:|||||||| ||||||||||| ||| |||| |||| | ||||||||||||||:
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQ-EPDSSAGIGKSGAQPAKKRLNFGQTGDT 179
Qy 181 ESVPDPQPIGEPPAGPSGLGSGTMAAGGGAPMADNNEGADGVGSSSGNWHCDSTWLGDRV 240
|||||||||||||| |||:|| |||:|||||:||||||||||||||||||||| ||||||
Db 180 ESVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRV 239
Qy 241 ITTSTRTWALPTYNNHLYKQISNGTSGGSTNDNTYFGYSTPWGYFDFNRFHCHFSPRDWQ 300
||||||||||||||||||||||| |||||:||| ||||||||||||||||||||||||||
Db 240 ITTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQ 299
Qy 301 RLINNNWGFRPKRLNFKLFNIQVKEVTQNEGTKTIANNLTSTIQVFTDSEYQLPYVLGSA 360
||||||||||||||||||||||||||| | | ||||||||||:||||||:||||||||||
Db 300 RLINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSA 359
Qy 361 HQGCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFEFSYNFED 420
|:||||||||||||||||||||||:|||||||||||||||||||||||||||:||| ||:
Db 360 HEGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFEN 419
Qy 421 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNW 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 420 VPFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNW 479
Qy 481 LPGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSS 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 LPGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSS 539
Qy 541 GVLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 GVLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNS 599
Qy 601 QGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGLKHPPPQILIKNTPVPADP 660
|||||||||||||||||||||||||||||||||||||||||:||||||||||||||||||
Db 600 QGALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADP 659
Qy 661 PTTFNQAKLASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSTNVDFAVNTE 720
|| ||: || |||||||||||||||||||||||||||||||||||||||| ||:||||||
Db 660 PTAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTE 719
Qy 721 GTYSEPRPIGTRYLTRNL 738
| ||||||||||||||||
Db 720 GVYSEPRPIGTRYLTRNL 737
INSTANT SEQ ID NO: 2 (Qy) vs Patent SEQ ID NO: 3 (Db)
Query Match 100.0%; Length 737; Matches 737; Mismatches 0; Gaps 0
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
Qy 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
Qy 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
Qy 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
Qy 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNWL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSRTQSTGGTAGTQQLLFSQAGPNNMSAQAKNWL 480
Qy 481 PGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSSG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PGPCYRQQRVSTTLSQNNNSNFAWTGATKYHLNGRDSLVNPGVAMATHKDDEERFFPSSG 540
Qy 541 VLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNSQ 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 VLMFGKQGAGKDNVDYSSVMLTSEEEIKTTNPVATEQYGVVADNLQQQNAAPIVGAVNSQ 600
Qy 601 GALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPP 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GALPGMVWQNRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPP 660
Qy 661 TAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 TAFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEG 720
Qy 721 VYSEPRPIGTRYLTRNL 737
|||||||||||||||||
Db 721 VYSEPRPIGTRYLTRNL 737
Prosecution Insights