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 .
DETAILED ACTION
The claim set filed 10/27/2023 is acknowledged.
Claims 5-6 and 9-18 are withdrawn by the examiner as being improper multi-dependent claims.
Claims 1-4, 7-8, and 19-20 will be examined on the merits herein.
Specification
The use of the term Adcetris p.56 line 13, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
It should be noted that the cited occurrences of improper use are only exemplary and Applicant should review the entire specification to correct any other improper use of trademarks.
Claim Objections
Claim 2 is objected to for referring to a cytotoxic which is an adjective not a noun. The objection can be overcome by referring to a cytotoxic agent. In the interest of compact prosecution, the examiner will interpret claim 2 as referring to a cytotoxic agent.
Claim 3 is objected to because the first letter “A” is capitalized in each of the steps a)-c). This is not the beginning of a sentence and therefor it should not be capitalized. Claim 3 is also objected to because the preamble recites “A polynucleotide selected in the group” which would be clearer written as “A polynucleotide selected from the group”.
Claims 5-6 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claims 9-18 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claim Rejections - 35 USC § 112(b)
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 8 is 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.
Claims 8 is indefinite because it used exemplary language. The claim uses the terms preferably and more preferably, it is unclear if these are limitations. Preferred embodiments should be detailed in the specification, not the claims.
Claim Rejections - 35 USC § 103
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.
Claims 1 and 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020016459 A1 (Published 1/23/2020) hereinafter 459 in view of Kretschmer et al (Antibody Isotypes for Tumor Immunotherapy, Transfus Med Hemother 2017;44:320–326 DOI: 10.1159/000479240, 9/7/2017).
Regarding claim 1, 459 teaches an anti-VISTA antibody which comprises heavy and light chain CDRs listed in table 5. p.76 par.3 and p.78 table 5. In this table the IMGT column contains all the CDRs of the instant applications claim 1. Specifically, the instant application defines the heavy chain CDRs of SEQ ID NO: 21 on p.63 line 16 as SEQ ID NO: 13-15, which are 100% identical to 459 SEQ ID NO: 6, 32, and 16 respectively. The instant application defines the light chain CDRs of SEQ ID NO: 22 on p.63 line 22 as SEQ ID NO: 16-18. which are 100% identical to 459 SEQ ID NO: 20, 24 and 26 respectively.
It is noted that SEQ ID NO: 21 contains aspartic acid (asp or D) in place of asparagine (asn or N) in CDR2 (this is the heavy chain) specification p.44, lines 13-15. This is position 55 of the SEQ ID NO: 21, p.4 line 1. This substitution is important as the inventor’s draw attention to it, as it prevents deamination. The same amino acid exists in 459 heavy chain CDR2 SEQ ID NO: 32 at position 5, bolded for emphasis below.
The examiner has provided an annotated sequences for demonstration purposes: CDRs are underlined, and the aspartic acid at position 55 in VH CDR2 is bolded.
SEQ ID NO: 21 VH
(QVQLVQSGAEVKKPGASVKISCKASGFSFTGYTMNWVRQAPGQGLEWIGLISPYDGGTSYAQKFQGRATLTVDTSTSTAYMELSSLRSEDTAVYYCARRAYGYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK)
459 VH CDR1 SEQ ID NO: 13 (GFSFTGYT)
459 VH CDR2 SEQ ID NO: 32 (ISPYDGGT)
459 VH CDR3 SEQ ID NO: 16 (ARRAYGYAMDY)
SEQ ID NO: 22 VL
(EIVLTQSPATLSLSPGERVTMSCSASSSVSYMYWYQQKPGQAPRLLIYDTSNLASGVPARFSGSGSGTDYTLTISSMEPEDFAVYYCQQWSSYPFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC)
459 VL CDR1 SEQ ID NO: 20 (SSVSY)
459 VL CDR2 SEQ ID NO: 24 (DTS)
459 VL CDR3 SEQ ID NO: 26 (QQWSSYPFT)
It is noted that SEQ ID NO: 21 is a human IgG1 heavy chain as demonstrated by a NCBI BLAST search of the amino acids from position 107 to the end, this corresponds to the positions after the end of CDR3 which would include framework region 4 and the Fc region.
Blast search image below:
PNG
media_image1.png
896
1392
media_image1.png
Greyscale
459 does not teach the full exact sequence of SEQ ID NO: 21 and 22, however claim 1 is drawn to sequences represented by SEQ ID NO: 21 and 22, represented by can be interpreted to mean a sequence which has the same CDRs which are the most important part of the variable region of an antibody and define its binding to a target.
Kretschmer teaches human IgG1 antibodies demonstrated favorable biotechnological characteristics such as high production rates in transfectoma cells (e.g. Chinese hamster ovary (CHO) cells), easy and cost-effective purification (e.g. by protein A columns), and development of specific storage formulations for increased stability, p.321 last paragraph, p.322 first paragraph.
It would have been obvious to a person having ordinary skill in the art to combine the antibody CDRs of 459 with a human IgG1 antibody framework and Fc region to arrive at a sequence represented by SEQ ID NO: 21 and 22. A person having ordinary skill in the art would have been motivated to do this in order to achieve the aforementioned high production rates, and cost-effective purification p.321 last paragraph, p.322 first paragraph.
There would have been reasonable expectation of success because Kretschmer teaches that many IgG1 antibodies are in use on p.322 table 1.
Regarding claims 3-4, 459 teaches “Polynucleotides of the invention and vectors comprising these molecules can be used for the transformation of a suitable host cell. The term "host cell", as used herein, is intended to refer to a cell into which a recombinant expression vector has been introduced in order to express the present antibody (e.g., an anti-PSGL-1 antibody or an anti-VISTA antibody)” p.83 lines 15-19. It would have been obvious to produce the above anti-VISTA antibodies with expression vectors in a host cell because 459 teaches this method of production.
Claims 2, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over 459 in view of Kretschmer as applied to claim 1 above, in further view of US Patent US 10577424 B1 (published 3/3/2020) hereinafter 424.
Regarding claim 2, As indicated above 459 and Kretschmer teach claim 1. They do not teach the anti-VISTA antibody conjugated to a cytotoxic agent.
424 teaches an isolated monoclonal antibody or the antigen binding portion thereof that specifically binds human VISTA p.9 col.1 lines 6-7. 424 teaches an anti-VISTA antibody had-anti tumor activity in example 13 p.24 col.32 lines 22-25 and fig.7. 424 teaches VISTA is highly expressed in the tumor micro environment p.9 col.1 lines 40-41. 424 suggests treatment of cancer with humanized anti-VISTA antibodies that may be administered with a cytotoxic agent p.10 col.4
A person having ordinary skill in the art would have been motivated to combine the anti-VISTA antibody of claim 1 with a conjugated cytotoxic agent to treat tumors because conjugating the cytotoxic agent would ensure it stays with the antibody when arriving at the site of the tumor.
There would have been a reasonable expectation of success because 424 teaches monotherapy with a blocking anti-VISTA antibody inhibited tumors in many animal models, p.9 col.1 lines 46-48, and there are standard cytotoxic agents administered for cancer p.19 col.21 lines 62-67, and col.22 lines 1-3.
Regarding claims 7 and 8, 459 teaches pharmaceutical compositions including buffers for stabilizing and storing the composition and to make sure the composition is nontoxic to a recipient. It would have been obvious to a person having ordinary skill in the art to make these compositions. p.92 lines 8-28
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over 459 in view of Kretschmer as applied to claim 1 above, in further view of patent application WO 2015097536 A2 (published 6/2/2015) hereinafter 536.
Regarding claims 19 and 20, As indicated above 459 and Kretschmer teach claim 1. They do not teach an in vitro method of detecting cancer with the anti-VISTA antibody.
536 teaches detection of vista expression in lung tumors with anti-VISTA antibodies in example 22 par.354-357 The anti-VISTA antibody was detected with using a rabbit anti-mouse polyclonal antibody, followed by anti-rabbit polymer HRP label.
A person having ordinary skill in the art would have been motivated to use the anti-vista antibodies to detect cancer that is mediated by VISTA in order to diagnose cancer and make sure the treatment using an anti-VISTA antibody is only applied in VISTA mediated cancers. This would be a simple substitution of one anti-VISTA antibody for another one.
There would have been a reasonable expectation of success because detection was shown to work in 536 example 22 par.354-357.
Nonstatutory 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.
Provisional Double Patenting
18806426 Double Patenting
Claims 1-8, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-22 of copending U.S. Application No. 18806426, in view of 459 in view of Kretschmer in further view of 424 and 536.
Regarding claims 1, Although the claims at issue are not identical, they are not patentably distinct from each other because 18806426 claims an anti-VISTA antibody comprising the same CDRs as the instant application. The VH and VL sequences of 18806426 claim 16 are depicted below with the CDRs of the instant application underlined, they are 100% identical.
18806426 SEQ ID NO:30 with instant CDRs SEQ ID NO: 16-18 underlined.
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMYWYQQKPGSSPRLLIYDTSNLASGVPLRFSGSGSGTSYSLTISRMEAEDAATYYCQQWSSYPFTFGSGTKLEIK
18806426 SEQ ID NO:30 with instant CDRs SEQ ID NO: 13-15 underlined.
EVQLQQSGPELVKPGASMKISCKASGFSFTGYTMNWVKQSHVKNLEWIGLISPYDGGTSYNQKFKGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARRAYGYAMDYWGQGTSVTVSS
18806426 claim 15 is drawn to a humanized antibody which would include IgG1. It would have been obvious for a person having ordinary skill in the art to use the CDRs of 18806426 in a human IgG1 to arrive at an antibody represented by the sequences of instant claim 1 for the reasons established in the 103 rejection of claim 1 above.
Regarding claim 2, see the 103 rejection for claim 2 above.
Regarding claim 3, 18806426 claim 17 teaches a polynucleotide encoding the antibody.
Regarding claim 4, 18806426 claim 18 teaches a vector.
Regarding claim 5, 18806426 claim 19 teaches a host cell.
Regarding claim 6, 18806426 claim 20 teaches a method of preparing the antibody.
regarding claim 7, 18806426 claim 21 teaches a pharmaceutical composition.
Regarding claim 8, 18806426 does not teach a buffering agent, however it would have been obvious in view of the 103 rejection of claim 8 above.
Regarding claim 19 and 20, see the rejections for claims 19 and 20 in the 103 rejection above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
The images below color code the heavy chain features of instant SEQ ID NO: 21 as compared to the CDRs of 459 in table 5. p.76 par.3 and p.78 table 5.
PNG
media_image2.png
501
1177
media_image2.png
Greyscale
Table 5 of 459 below shows the relevant CDRs with the IMGT VH CDR2 highlighted in green and the differing amino acids in the Kabat CDR scheme highlighted in red.
PNG
media_image3.png
437
906
media_image3.png
Greyscale
A sequence that is represented by SEQ ID NO: 21 can be considered to have some substitutions. However, a person having ordinary skill in the art would not have known to make the specific N to A substitution and K to Q substitution in order to arrive at the exact variable heavy sequence comprising SEQ ID NO: 21 if the claims were written without allowing for any substitutions.
Therefore, the complete sequence of SEQ ID NO: 21 and 22 would be allowable subject matter if the broader term “represented by” was removed from the claim language and limited to comprising in order to make the sequences exactly as detailed in SEQ ID NO: 21-22.
Conclusion
No claims are allowed.
Inquiry Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUDOLPH E. SLOUP Jr. IV Ph.D. whose telephone number is (571)272-7899. The examiner can normally be reached Monday to Friday, 10am to 5pm.
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, Joanne Hama can be reached at (571) 272-2911. 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.
/RUDOLPH E. SLOUP Jr. IV Ph.D./
Examiner, Art Unit 1645
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights