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 .
Response to Amendment/Disposition of Claims
Applicant’s Amendment filed on 11 November 2024 has been received and entered. Claims 1-9, 11, and 13-22 were pending. Claims 1, 4, 9, 13, 16-17, and 22 have been amended. Claims 2-3, 10, and 12 have been cancelled. New claim 23 has been added.
Accordingly, Claims 1, 4-9, 11, and 13-23 are pending and will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2021/0301000, Published 30 September 2021. Applicant’s amended Specifications as presented on 09 February 2021, 26 April 2024, and 11 November 2024 are acknowledged.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Response to Arguments
Applicant's arguments filed 11 November 2024 regarding the previous Office action dated 31 July 2024 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 29 August 2018. It is noted, however, that applicant still has not filed a certified copy of the English translation of the CN201810999045.2 application as required by 37 CFR 1.55.
Should applicant desire to obtain the full benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). While an English translation is not required unless an interference has been raised, it is suggested that one be filed of record to perfect the foreign priority effective filing date. Applicant is reminded that in the event that intervening art is found that falls between the foreign priority filing date and the 371 filing date, a prior art rejection may be raised since the certified copy of the foreign priority documents is not in English and an English translation of said documents has not been provided.
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Response to Arguments
Applicant's arguments filed 11 November 2024 have been fully considered but they are not persuasive.
In their Response, Applicant argues that the “certified copy of the English translation of the CN201810999045.2 has been provided” (See Page 5 of Remarks, Paragraph 2). However, this submission is incomplete in that the required statement per 37 CFR 1.55(g) (4) stating that “(4) If an English language translation of a non-English language foreign application is required, it must be filed together with a statement that the translation of the certified copy is accurate.” As such, the Foreign Priority has still not been perfected because the statement verifying that the translation is accurate is missing.
Specification
(Objection withdrawn) – The objection to the disclosure for containing possible minor errors is withdrawn in light of the amendments to the Specification.
Claim Objections
(Objection withdrawn) – The objection to Claims 1 and 13 for containing undefined abbreviations is withdrawn in light of the amendments to the claims.
(Objection withdrawn) – The objection to Claims 1-2, 9, and 13 is withdrawn in light of the amendments to the claims and the cancellation of one of the claims.
(New Objections) – Claims 1, 9, 17, and 22 are objected to because of the following informalities: In Claim 1, it should say “…selected from the following amino acid sequences, wherein the complementarity…” instead of “…selected from the following amino acid sequences, the complementarity…”.
In Claim 9, it should say “…culturing the isolated host cell comprising the nucleic acid…” instead of “…culturing a host cell comprising a nucleic acid…”.
In Claim 17, it should say “…according to claim 1, wherein in the complementarity…” instead of “…according to claim 1, wherein the complementarity…”.
In Claim 22, it should say “…SEQ ID NOs: 1-4, successively,…SEQ ID NOs: 5-8, successively”. Commas should be added after the numbers. Also, the strikethrough of “4” is not clear and the claim can be reasonably interpreted to read as “according to claim 41”. It is suggested that Applicant use double brackets, “[[]]”, going forward when deleting single characters such as individual numbers.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
(Rejection maintained in part) – The rejection of Claims 1-2, 17, and 20, and dependent claims 2-9, 11, and 13-22 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is maintained in part.
(Rejection withdrawn) – The rejection of Claims 1-2 and 17, and dependent claims 2-9, 11, and 13-22 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims and the cancellation of two of the claims.
(Rejection withdrawn) – The rejection of Claim 2 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claim.
(Rejection withdrawn) – The rejection of Claim 4, and dependent claim 22 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
(Rejection withdrawn) – The rejection of Claim 4, and dependent claim 22 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
(Rejection withdrawn) – The rejection of Claims 16-17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
Response to Arguments
Applicant's arguments filed on 11 November 2024 have been fully considered but they are not persuasive.
In their Response, Applicant fails to present any arguments regarding the rejection of Claims 17 and 20. As such, the rejection of Claims 1-2 and 17, and dependent claims 2-9, 11, and 13-22 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn as it relates to Claims 1-2, and dependent claims 2-9, 11, and 13-22 thereof, in light of the amendments to the claims, but is maintained as it relates to Claims 17 and 20 for reasons of record. With regard to Claim 17, the claim could be amended to recite “wherein the remaining variable amino acids in the CDRs are selected from the mutations listed below:…” or something similar to clarify the claim language. As currently written, there are additional permutations of variables being claimed. With regard to Claim 20, it is suggested that the Claim be amended to recite “wherein the antibody constant region is derived from mouse antibody constant regions, wherein the mouse light chain constant region is SEQ ID NO: 9 and wherein the mouse heavy chain constant region is SEQ ID NO: 10”.
(New Rejection) – Claims 1 and 17, and dependent claims 4-9, 11, and 13-23 thereof, 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 Claims 1 and 17, they recite an antigen binding protein comprising CDRs without specifying which CDR numbering system was used to generate said CDRs. As the specific CDRs generated from an antibody’s VH and/or VL sequences can vary depending on the numbering system used (see Dondelinger et al., 2018, especially Figure 6; Dondelinger, M., Filée, P., Sauvage, E., Quinting, B., Muyldermans, S., Galleni, M., & Vandevenne, M. S. (2018). Understanding the Significance and Implications of Antibody Numbering and Antigen-Binding Surface/Residue Definition. Frontiers in Immunology, 9, 2278–2278.), it is unclear what is and what is not encompassed by the claims. It is suggested that the claims be amended by specifying which CDR numbering system was used to generate said CDRs, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1 and 17 are rejected on the grounds of being indefinite. Claims 4-9, 11, and 13-23 are also rejected since they depend upon Claim 1, but do not remedy the deficiencies of Claim 1.
(New Rejection – necessitated by amendment) – Claims 1, 4-6, 9, 11, 13, 17-19, and 21, and dependent claims 4-9, 11, and 13-19, and 21 thereof, 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 Claims 1, 4-6, 9, 11, 13, 17-19, 21, they recite the limitation of a “binding protein”, which is a relative term, rendering the claim indefinite. The term “binding protein” is not defined in the claims themselves, no clear definition is provided in the Specification, and the dissociation constant was removed from Claim 1 in the amended claim set. This dissociation constant, which is now recited in new Claim 23, clearly defined what was, and what was not, considered a “binding protein” as it provided a standard to determine if the protein “bound” to the NS1 protein by stating that the “binding protein” had a dissociation constant (KD) ≤6.55x10-8 mol/L. Since this limitation has been removed, however, the metes and bounds of what is, and what is not, a “binding protein” are now unclear. It is suggested that the claims, specifically Claim 1, be amended to once again recite the dissociation constant, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1, 4-6, 9, 11, 13, 17-19, and 21 are rejected on the grounds of being indefinite. Claims 4-9, 11, and 13-19, and 21 are also rejected since they depend upon Claim 1, but do not remedy the deficiencies of Claim 1.
Claim Interpretation
In light of the issues raised supra, the claims are being interpreted as reading upon the following:
Claim 1 is drawn to an isolated binding protein comprising an dengue virus nonstructural protein 1 antigen binding domain, wherein the antigen binding domain comprises six complementarity determining regions selected from the following amino acid sequences, wherein the complementarity determining region CDR1-VH is SEQ ID NO: 13: G-Y-X1-F-T-X2- Y-W-I-G, wherein, X1 is S or T, and X2 is D or E; the complementarity determining region CDR2-VH is SEQ ID NO: 14: D-M-X1-P-G-D-X2 -Y-I-N-Y-X3-E-K-F-K-G, wherein, X1 is F or V, X2 is V, L or I, and X3 is Q or N; the complementarity determining region CDR3-VH3 is SEQ ID NO: 15: T-N-F-X1-T-X2- G-G-X3-D-Y, wherein, X1 is I or L, X2 is L or V, and X3 is V, L or I; the complementarity determining region CDR1-VL is SEQ ID NO: 16: K-S-S-X1-S-L-L-X 2-S-D-G-X3-T-Y-L-N, wherein, X1 is Q or N, X2 is E or D, and X3 is R or K; the complementarity determining region CDR2-VL is SEQ ID NO: 17: L-V-X1-K-X2-D-S, wherein, X1 is S or T, and X2 is V, I or L; and the complementarity determining region CDR3-VL is SEQ ID NO: 18: W-X1-G-T-H-F- X2-H-T, wherein, X1 is Q, Y or W, and X2 is A or P.
Further limitations on the isolated binding protein according to Claim 1 are:
4. The binding protein according to claim 1, wherein the binding protein is one of F(ab')2, Fab', Fab, Fv, scFv or a bispecific antibody.
5. The binding protein according to claim 1, wherein the binding protein further comprises an antibody constant region sequence.
6. An isolated nucleic acid encoding the binding protein according to claim 1.
7. A vector comprising the nucleic acid according to claim 6.
8. A host cell comprising the nucleic acid according to claim 6.
9. A method for producing the binding protein according to claim 1, wherein, the method comprises the following steps: culturing the isolated host cell comprising the nucleic acid encoding the binding protein according to claim 1 in a culture medium, and recovering the produced binding protein from the culture medium or from the cultured host cell.
11. A kit comprising one or more of the binding protein according to claim 1.
13. A method for detecting a dengue virus nonstructural protein 1 comprising: A) contacting a sample from a subject with the binding protein according to claim 1 for performing a binding reaction in a condition sufficient for a binding reaction; and B) detecting an immune complex generated by the binding reaction, wherein the presence of the immune complex is indicative of the presence of the dengue virus nonstructural protein 1.
14. The method according to claim 13, wherein the method is based fluorescence immunoassay, a chemiluminescence immunoassay, a colloidal gold immunoassay, a radioimmunoassay and/or an enzyme-linked immunoassay.
15. The method according to claim 13, wherein the sample is selected from at least one of whole blood, peripheral blood, serum, or plasma.
16. The method according to claim 13, wherein the subject is a mammal.
17. The binding protein according to claim 1, wherein in the complementarity determining region CDR1-VH, X1 is T; in the complementarity determining region CDR2-VH, X1 is F; in the complementarity determining region CDR3-VH, X2 is L; in the complementarity determining region CDR1-VL, X2 is D; in the complementarity determining region CDR2-VL, X1 is S; or in the complementarity determining region CDR3-VL, X2 is P; wherein the remaining variable amino acids in the CDRs are selected from the mutations listed below:
PNG
media_image1.png
597
1002
media_image1.png
Greyscale
PNG
media_image2.png
193
893
media_image2.png
Greyscale
PNG
media_image3.png
347
905
media_image3.png
Greyscale
PNG
media_image4.png
400
912
media_image4.png
Greyscale
18. The binding protein according to claim 5, wherein the antibody constant region sequence is selected from the sequence of any one of the constant regions of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, and IgD.
19. The binding protein according to claim 5, wherein a species source of the antibody constant region is cow, horse, dairy cow, pig, sheep, goat, rat, mouse, dog, cat, rabbit, camel, donkey, deer, mink, chicken, duck, goose, turkey, gamecock, or human.
20. The binding protein according to claim 5, wherein the antibody constant region is derived from mouse antibody constant regions, wherein the mouse light chain constant region is SEQ ID NO: 9 and wherein the mouse heavy chain constant region is SEQ ID NO: 10.
21. The binding protein according to claim 1, wherein the binding protein is labeled with an indicator for displaying signal intensity.
22. The binding protein according to claim 1, wherein the binding protein comprises the light chain framework regions FR1-VL, FR2-VL, FR3-VL, and FR4-VL with sequences shown in SEQ ID NOs: 1-4, successively, and/or the heavy chain framework regions FR1-VH, FR2-VH, FR3-VH, and FR4-VH with sequences shown in SEQ ID NOs: 5-8, successively.
23. The binding protein according to claim 1, wherein the binding protein has an affinity of the equilibrium dissociation constant ≤6.55x10-8 mol/L to the dengue virus nonstructural protein 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
(New Rejection) – Claim 8 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 8 recites the limitation of “A host cell”, which reads upon a human organism and human organisms are not patentable subject matter. It is suggested that the claim be amended to recite “An isolated host cell”, which would not read upon a human organism.
Claim Rejections - 35 USC § 112(a); First Paragraph
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.
(Rejection withdrawn) – The rejection of Claims 1-9, 11, and 13-22 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 is withdrawn in light of the amendments to the claims and the cancellation of two of the claims.
(Rejection withdrawn) – The rejection of Claims 1-9, 11, and 13-22 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for being enabling for detecting the NS1 protein of Dengue virus serotypes 1-4, but not being enabling for detecting any NS1 protein is withdrawn in light of the amendments to the claims and the cancellation of two of the claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAREY A STUART whose telephone number is (703)756-4668. The examiner can normally be reached Monday - Friday, 7:30 AM - 4:30 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet Andres can be reached on 5712720867. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CAREY ALEXANDER STUART/Examiner, Art Unit 1671
/RACHEL B GILL/Primary Examiner, Art Unit 1671