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
Acknowledgement is hereby made of receipt and entry of the communication filed on Oct. 20, 2023. Claims 1-26 are pending and currently examined.
Claim Objection
A. Non-Compliance with the Sequence Rules
Claims 1 and 17-23 are objected to for reciting sequences without also identifying them by the sequence identifier assigned to them in the sequence listing as required by 37 CFR 1.821(d). The examiner would like to bring the applicant's attention to the following excerpt from MPEP §2422.03:
37 CFR 1.821(d) requires the use of the assigned sequence identifier in all instances where the description or claims of a patent application discuss sequences regardless of whether a given sequence is also embedded in the text of the description or claims of an application. This requirement is also intended to permit references, in both the description and claims, to sequences set forth in the "Sequence Listing" by the use of assigned sequence identifiers without repeating the sequence in the text of the description or claims. Sequence identifiers can also be used to discuss and/or claim parts or fragments of a properly presented sequence. For example, language such as "residues 14 to 243 of SEQ ID NO:23" is permissible and the fragment need not be separately presented in the "Sequence Listing." Where a sequence is embedded in the text of an application, it must be presented in a manner that complies with the requirements of the sequence rules.
These claims recite amino acid sequences, e.g., MPMGSLQPLATLYLLGMLVASVLA, MDAMKRGLCCVLLLCGAVFVSP, and MGSLQPLATLYLLGMLVASVLA. While MPMGSLQPLATLYLLGMLVASVLA is given SEQ ID NO: 9 (see [0109]), the other two sequences are without sequence identifiers.
The applicant is therefore required to amend the claims or specification to comply with 37 CFR 1.821(d).
B. Minor Abnormality
Claim 26 recites an abbreviation “LNP” which is not spelled out the first time it appears in the claims set.
Appropriate correction is required.
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.
Claims 1-26 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. This rejection has the following grounds.
A. Base claim 1 recites “A recombinant HIV-1 envelope comprising: the amino acids of SEQ ID NO: 100……” Here, the phrase “recombinant HIV-1 envelope” renders the claims unclear. An HIV envelope is the outer layer of the virus comprising a lipid membrane studded with protein spikes (e.g., Env glycoproteins). Thus, it is not clear if the claimed “recombinant HIV-1 envelope” refers to the entire envelope including a recombinant protein set forth by the recited sequences, or only a recombinant HIV envelope protein itself. To facilitate examination, the claimed “recombinant HIV-1 envelope” is interpreted as referring to a “recombinant envelope protein” that can be potentially incorporated into the HIV-1 envelope. (This interpretation agrees better with succeeding dependent claims which more clearly imply that the claimed “envelope” refers to an “envelope protein” (see e.g., claim 3).)
B. These claims recite the phrase “all the consecutive amino acids immediately after the signal peptide”. Since this phrase does not require a specific sequence, it is not clear if this phrase refers to the amino acid sequences specified in the sequence identifiers or a combination of a bunch consecutive amino acids. If the claims are intended to specify that the claimed HIV-1 envelope may comprise the sequence of the specified identifiers lacking the specified N-terminal signal peptide sequences, Applicant may consider using a different wording, e.g., for claim 1, “A recombinant HIV-1 envelope protein comprising: the amino acid sequence of SEQ ID NOs: 100, 101, 102 or 103; the amino acid sequence of SEQ ID NOs: 135-40, 157, 159, 160, 162, 163, 165, or 176-185, lacking the N-terminal amino acids 1-24; the amino acid sequence of SEQ ID NOs: 141-146, 152-156, 158, 161, 164 or 195, lacking the N-terminal amino acids 1-22; the amino acid sequence of SEQ ID NOs: 147-151 or 191, lacking the N-terminal amino acids 1-22; or the amino acid sequence of SEQ ID NO: 194, lacking the N-terminal amino acids 1-24.”
C. Claim 2 recites “wherein the envelope is a promoter comprised in a trimer”. This limitation is not clear since it is not clear how an “envelope” can be a promoter, which is a structure on nucleic acid level to control the gene expression. To facilitate examination, the phase “wherein the envelope is a promoter comprised in a trimer” is considered as being equivalent to “wherein the envelope protein is in a trimer”.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Rejections - 35 USC § 112(a)
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 1-15 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 claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 1, as amended in the version submitted on Oct. 20, 2023, introduces new matter.
Claim 1 is drawn to a recombinant HIV-1 envelope (protein) comprising “all the consecutive amino acids immediately after the signal peptide” of one of the signal peptide sequences of one of the protein sequences with the recited sequence identifiers. It is noticed that [0109] of the specification teaches “A skilled artisan appreciates that when used as immunogens, and for example when recombinantly produced, the amino acid sequences of these proteins do not comprise the leader peptide sequences." This teaching is not considered sufficient in supporting the claimed sequences since the specification does not disclose all of the claimed sequences lacking the respective signal peptides.
Accordingly, claims 1-15 are rejected for containing new matter.
Claim Rejections - 35 USC § 102
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.
Claims 1-15 are rejected under 35 U.S.C. 102 as being anticipated by Kwong et al. (US 2017/0233441 A1, published on Aug. 17, 2017).
These claims are drawn to a recombinant HIV-1 envelope (protein) comprising: the amino acids of SEQ ID NOs: 100, 101, 102 or 103; all the consecutive amino acids immediately after the signal peptide MPMGSLQPLATLYLLGMLVASVLA of SEQ ID NOs: 135-140, 157, 159, 160, 162, 163, 165, or 176-185; all the consecutive amino acids immediately after the signal peptide MDAMKRGLCCVLLLCGAVFVSP of SEQ ID NOs: 141-146, 152-156, 158, 161, 164 or 195; all the consecutive amino acids immediately after the signal peptide MGSLQPLATLYLLGMLVASVLA of SEQ ID NOs: 147-151 or 191; or all the consecutive amino acids immediately after the signal peptide MPMGSLQPLATLYLLGMLVASVLA of SEQ ID NO: 194.
As indicated in the 112(b) rejection above, the term “recombinant HIV-1 envelope” is interpreted as referring to a recombinant envelope protein comprising one of the claimed sequences.
Kwong teaches an invention relating to HIV-1 Env ectodomain trimers stabilized in a prefusion mature closed conformation and methods of their use and production. The HIV-1 Env ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject. The therapeutically effective amount of the HIV-1 Env ectodomain trimers can be administered to a subject in a method of treating or preventing HIV-1 infection. See Abstract.
Kwong teaches that, in some embodiment, the recombinant HIV-1 Env ectodomain trimer stabilized in the prefusion mature closed conformation can be included on a protein nanoparticle, such as a ferritin or lumazine synthase protein nanoparticle. Nucleic acid molecules encoding the recombinant HIV-1 Env ectodomain trimer stabilized in the prefusion mature closed conformation and vectors including the nucleic acid molecules are also provided. Compositions including the recombinant HIV-1 Env ectodomain trimer or immunogenic fragments thereof, protein nanoparticles, nucleic acid molecules or vectors are also provided. The composition may be a pharmaceutical composition suitable for administration to a subject, and may also be contained in a unit dosage form. The compositions can further include an adjuvant. The recombinant HIV-1 Env ectodomain trimers may also be conjugated to a carrier to facilitate presentation to the immune system. See [0013].
Kwong teaches a recombinant polypeptide, SEQ ID NO: 1101, that comprises the instant SEQ ID NO: 135 lacking the N-terminal 1-24 amino acids. See the in-house sequence search result below:
RESULT 1
US-15-508-885A-1101
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1101, US/15508885A
Patent No. 10400015
GENERAL INFORMATION
APPLICANT: The Government of the United States of America as
APPLICANT: represented by the Secretary, Department of Health and Human
APPLICANT: Services
TITLE OF INVENTION: RECOMBINANT HIV-1 ENVELOPE PROTEINS AND THEIR USE
FILE REFERENCE: 4239-93065-05
CURRENT APPLICATION NUMBER: US/15/508,885A
CURRENT FILING DATE: 2017-04-19
PRIOR APPLICATION NUMBER: PCT/US2015/048729
PRIOR FILING DATE: 2015-09-04
PRIOR APPLICATION NUMBER: 62/046,059
PRIOR FILING DATE: 2014-09-04
PRIOR APPLICATION NUMBER: 62/136,480
PRIOR FILING DATE: 2015-03-21
NUMBER OF SEQ ID NOS: 2159
SEQ ID NO 1101
LENGTH: 799
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Recombinant HIV protein
Query Match 96.7%; Score 3377; Length 799;
Best Local Similarity 100.0%;
Matches 631; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 25 AENLWVTVYYGVPVWEDADTPLFCASDAKAYSTESHNVWATHACVPTDPSPQEISLDNVT 84
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AENLWVTVYYGVPVWEDADTPLFCASDAKAYSTESHNVWATHACVPTDPSPQEISLDNVT 60
Qy 85 ENFNMWKNNMVEQMHEDIISLWDESLKPCVKLTPLCVTLNCTNVNNSSATNNSMVDDREG 144
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ENFNMWKNNMVEQMHEDIISLWDESLKPCVKLTPLCVTLNCTNVNNSSATNNSMVDDREG 120
Qy 145 LKNCSFNITTELRDKKKQEHALFYRLDIVPINGNSNSNSSVGDYRLINCNVSTCKQACPK 204
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LKNCSFNITTELRDKKKQEHALFYRLDIVPINGNSNSNSSVGDYRLINCNVSTCKQACPK 180
Qy 205 MSFDPIPIHYCAPAGFAILKCRDKKFNGTGSCKNVSTVQCTHGIKPVISTQLLLNGSVAE 264
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 MSFDPIPIHYCAPAGFAILKCRDKKFNGTGSCKNVSTVQCTHGIKPVISTQLLLNGSVAE 240
Qy 265 EEIMIRSENFTNNAKNIIVQFNKTIDIMCTRPNNNTRKSISLGPGQAIYATGDIIGNIRQ 324
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EEIMIRSENFTNNAKNIIVQFNKTIDIMCTRPNNNTRKSISLGPGQAIYATGDIIGNIRQ 300
Qy 325 AHCNISGADWGNMIRNVSEKLKEIFNKTTITFKASAGGDLEITTHSFNCRGEFFYCDTSD 384
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 AHCNISGADWGNMIRNVSEKLKEIFNKTTITFKASAGGDLEITTHSFNCRGEFFYCDTSD 360
Qy 385 LFNSSRFNNSSNDTNDTITLPCKIKQIVRMWQRVGQCMYAPPIAGNITCRSNITGLLLTR 444
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LFNSSRFNNSSNDTNDTITLPCKIKQIVRMWQRVGQCMYAPPIAGNITCRSNITGLLLTR 420
Qy 445 DGGGNNTNETETFRPAGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAV 504
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DGGGNNTNETETFRPAGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAV 480
Qy 505 GIGAVFLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEAQQHLLKLTVWGI 564
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GIGAVFLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEAQQHLLKLTVWGI 540
Qy 565 KQLQARVLAVERYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDK 624
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 KQLQARVLAVERYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDK 600
Qy 625 EISNYTQIIYGLLEESQNQQEKNEQDLLALD 655
|||||||||||||||||||||||||||||||
Db 601 EISNYTQIIYGLLEESQNQQEKNEQDLLALD 631
The sequence of SEQ ID No: 1101 of Kwong is presented below:
SEQ ID NO: 1101
AENLWVTVYYGVPVWEDADTPLFCASDAKAYSTESHNVWATHACVPTDPSPQEISLDNVTENFNMWKNNMVEQMHEDIISLWDESLKPCVKLTPLCVTLNCTNVNNSSATNNSMVDDREGLKNCSFNITTELRDKKKQEHALFYRLDIVPINGNSNSNSSVGDYRLINCNVSTCKQACPKMSFDPIPIHYCAPAGFAILKCRDKKFNGTGSCKNVSTVQCTHGIKPVISTQLLLNGSVAEEEIMIRSENFTNNAKNIIVQFNKTIDIMCTRPNNNTRKSISLGPGQAIYATGDIIGNIRQAHCNISGADWGNMIRNVSEKLKEIFNKTTITFKASAGGDLEITTHSFNCRGEFFYCDTSDLFNSSRFNNSSNDTNDTITLPCKIKQIVRMWQRVGQCMYAPPIAGNITCRSNITGLLLTRDGGGNNTNETETFRPAGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVFLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEAQQHLLKLTVWGIKQLQARVLAVERYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSGGDIIKLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKS
SEQ ID NO: 1101 of Kwong represents a recombinant fusion polypeptide comsisting of the amino acid sequence of instant SEQ ID NO: 135 lacking the N-terminal 24-aa signal peptide sequence (bold face), a linker GGSGG (italicized), and a ferritin peptide sequence (underlined).
Accordingly, Kwong teaches a recombinant HIV-1 envelope polypeptide comprising SEQ ID NO: 135 lacking the N-terminal signal peptide MPMGSLQPLATLYLLGMLVASVLA, fused to a ferritin peptide via a linker. Kwong also teaches that such polypeptides can be stabilized in trimer form, and can form ferritin nanoparticles. Kwong also teaches that such polypeptides, as well as nucleic acid encoding them, can be composed in pharmaceutical compositions for vaccine purposes.
Regarding claims 5 and 7-9, Kwong teaches that ferritin polypeptides assemble into a globular protein complex of 24 protein subunits, each of the 24 subunits includes a single ferritin polypeptide. In some examples, ferritin is used to form a nanoparticle presenting antigens on its surface, for example, an HIV antigen. See [0135]. Since the fusion protein of SEQ ID NO: 1101 in Kwong contains a timer-form HIV envelope domain and a ferritin domain, it is expected to form a ferritin-based nanoparticle comprising HIV envelope trimers.
Regarding claims 10-15, Kwong teaches that an immunotherapy can include administration of a first immunogenic composition (the primer vaccine) followed by administration of a second immunogenic composition (the booster vaccine) to a subject to induce an immune response. The primer vaccine and/or the booster vaccine include a vector (such as a viral vector, RNA, or DNA vector) expressing the antigen to which the immune response is directed. The booster vaccine is administered to the subject after the primer vaccine; the skilled artisan will understand a suitable time interval between administration of the primer vaccine and the booster vaccine, and examples of such timeframes are disclosed therein. In some embodiments, the primer vaccine, the booster vaccine, or both primer vaccine and the booster vaccine additionally include an adjuvant. In one non-limiting example, the primer vaccine is a DNA-based vaccine (or other vaccine based on gene delivery), and the booster vaccine is a protein subunit or protein nanoparticle-based vaccine. See [0181].
Therefore, Kwong teaches each and every aspect of claims 1-15.
Claims 1-15 are rejected under 35 U.S.C. 102 as being anticipated by Haynes et al. (US 11,246,920 B2, patented on Feb. 15, 2022; PCT publication date Sep. 8, 2017; referred to hereinafter as Hayes-2017) or Haynes et al. (US 11,318,197 B2, patented on May 3, 2022; PCT publication date Sep. 7, 2018; referred to hereinafter as Hayes-2018).
Both Haynes references disclose inventions relating to recombinant HIV-1 envelope protein sequences comprising amino acid substitutions and forming stabilized timers. See column 6, line 14-41 of Haynes-2017, and the Summary in Haynes-2018.
They both teach that a self-assembling ferritin peptide can be fused to a stabilized HIV-1 trimer. See column 62, lines 59-62 of Haynes-2017 and column 71, lines 15-27 of Haynes-2018. Both references teach various nucleic acid and amino acid sequences of various CH848 and other envelope trimer designs. See e.g., FIGs 39A-B, 40A-C and 41A-C in Haynes-2017 and the Summary in Haynes-2018.
More specifically, Hayes-2017 discloses some of the instantly claimed polypeptide sequences, e.g., SEQ ID NOs: 176, 177, 181, 182, 192, 193 and 194, respectively corresponding to SEQ ID NOs: 344, 345, 368, 369, 573, 325, and 338 of Haynes-2017; Haynes-2018 also discloses some of the instantly claimed polypeptide sequences, e.g., SEQ ID NOs: 176, 177, and 192, respectively corresponding to SEQ ID NOs: 344, 345 and 573 of Haynes-2018.
An in-house search result for SEQ ID NO: 176 is presented below:
RESULT 1
US-16-081-771-344
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 344, US/16081771
Patent No. 11246920
GENERAL INFORMATION
APPLICANT: DUKE UNIVERSITY
APPLICANT: LOS ALAMOS NATIONAL SECURITY, LLC
TITLE OF INVENTION: COMPOSITIONS AND METHODS FOR INDUCING HIV-1 ANTIBODIES
FILE REFERENCE: 1234300-00301US2
CURRENT APPLICATION NUMBER: US/16/081,771
CURRENT FILING DATE: 2020-06-29
PRIOR APPLICATION NUMBER: PCT/US2017/020823
PRIOR FILING DATE: 2017-03-03
PRIOR APPLICATION NUMBER: 62/403,649
PRIOR FILING DATE: 2016-10-03
PRIOR APPLICATION NUMBER: 62/303,273
PRIOR FILING DATE: 2016-03-03
NUMBER OF SEQ ID NOS: 524
SEQ ID NO 344
LENGTH: 652
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 100.0%; Score 3482; Length 652;
Best Local Similarity 100.0%;
Matches 652; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPMGSLQPLATLYLLGMLVASVLAAENLWVTVYYGVPVWKEAKTTLFCASDAKAYEKEVH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPMGSLQPLATLYLLGMLVASVLAAENLWVTVYYGVPVWKEAKTTLFCASDAKAYEKEVH 60
Qy 61 NVWATHACVPTDPSPQELVLKNVTENFNMWKNDMVDQMHEDIISLWDQSLKPCVKLTPLC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NVWATHACVPTDPSPQELVLKNVTENFNMWKNDMVDQMHEDIISLWDQSLKPCVKLTPLC 120
Qy 121 VTLNCSNARSNVNVTSINNTIMGEMKNCSFNTTTEIRDKEKKEYALFYKPDVVPLNETSN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTLNCSNARSNVNVTSINNTIMGEMKNCSFNTTTEIRDKEKKEYALFYKPDVVPLNETSN 180
Qy 181 TSEYRLINCNTSACTQACPKVTFEPIPIHYCAPAGYAILKCNNKTFNGTGPCSNVSTVQC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TSEYRLINCNTSACTQACPKVTFEPIPIHYCAPAGYAILKCNNKTFNGTGPCSNVSTVQC 240
Qy 241 THGIRPVVSTQLLLNGSLAEKEIVIRSENLTNNAKIIIVHLNTSVEIVCTRPGNNTRKSV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 THGIRPVVSTQLLLNGSLAEKEIVIRSENLTNNAKIIIVHLNTSVEIVCTRPGNNTRKSV 300
Qy 301 RIGPGQTFYATGDIIGDIRQAHCNISEGQWNKTLHEVSKELQKHFPNKTIKYERSAGGDM 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RIGPGQTFYATGDIIGDIRQAHCNISEGQWNKTLHEVSKELQKHFPNKTIKYERSAGGDM 360
Qy 361 EIATHSFNCGGEFFYCNTSNLFNGTYNGTYINTSSTSYITLQCRIKQIINMWQGVGRCMY 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EIATHSFNCGGEFFYCNTSNLFNGTYNGTYINTSSTSYITLQCRIKQIINMWQGVGRCMY 420
Qy 421 APPIAGNITCKSNITGLLLTRDGGTKNNSNEETFRPAGGDMRDNWRSELYKYKVVKIEPL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 APPIAGNITCKSNITGLLLTRDGGTKNNSNEETFRPAGGDMRDNWRSELYKYKVVKIEPL 480
Qy 481 GVAPTRCKRRVVGRRRRRRAVGIGAVFLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQ 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GVAPTRCKRRVVGRRRRRRAVGIGAVFLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQ 540
Qy 541 SNLLRAPEAQQHLLKLTVWGIKQLQARVLAVERYLRDQQLLGIWGCSGKLICCTNVPWNS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SNLLRAPEAQQHLLKLTVWGIKQLQARVLAVERYLRDQQLLGIWGCSGKLICCTNVPWNS 600
Qy 601 SWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD 652
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 SWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD 652
For the method claim 15, the Haynes references teach that nucleic acids encoding the claimed recombinant HIV-1 env proteins can be formulated for immunogenic purposes. E.g., Haynes-2017 teaches that the invention provides a nucleic acid encoding any one of the polypeptides of the invention, that the nucleic acids could be formulated in any suitable way for immunogenic delivery of nucleic acids, that invention provides an immunogenic composition comprising the nucleic acid of the invention and a carrier, and that the compositions could comprise an adjuvant. See column 4, lines 24-35.
Accordingly, Hayes-2017 and Hayes-2018, each individually teaches each and every aspect of claims 1-15.
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 of this title, 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.
Claims 16 and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Kwong et al. (US 2017/0233441 A1, published on Aug. 17, 2017), Haynes et al. (US 11,246,920 B2, patented on Feb. 15, 2022; PCT publication date Sep. 8, 2017; referred to hereinafter as Hayes-2017), and Haynes et al. (US 11,318,197 B2, patented on May 3, 2022; PCT publication date Sep. 7, 2018; referred to hereinafter as Hayes-2018).
Claim 16 is directed to a method of inducing an immune response in a subject comprising: administering a first immunogenic composition comprising a nucleic acid encoding SEQ ID NOs: 101 or 192 as a prime immunogen; and administering a second immunogenic composition comprising a nucleic acid encoding SEQ ID NOs: 102 or 193 as a boost immunogen, in an amount sufficient to induce an immune response.
Claims 24-26 further specify that immunogens of claim 16 are administered as nanoparticles or as a mRNA-LNP formulation.
Relevance of Kwong and the two Haynes references is set forth in the 102 rejections above. Briefly, they teach modified HIV envelope polypeptides stabilized for trimer formation. They also teach that such polypeptides can be fused with a ferritin peptide for self-assembling into nanoparticles. They further teach that the modified HIV envelope polypeptides or nucleic acids encoding them can be administered to a subject in multiple prime and boost steps. The two Haynes references further teach the sequences of SEQ ID NOs: 192 and 193, specified in instant claim 16. See discussion in the related 102 rejection above.
More specifically, the Haynes references teach that nucleic acids encoding the claimed recombinant HIV-1 env proteins can be formulated for immunogenic purposes. E.g., Haynes-2017 teaches that the invention provides a nucleic acid encoding any one of the polypeptides of the invention, that the nucleic acids could be formulated in any suitable way for immunogenic delivery of nucleic acids, that invention provides an immunogenic composition comprising the nucleic acid of the invention and a carrier, and that the compositions could comprise an adjuvant. See column 4, lines 24-35. Haynes-2017 further teaches that the invention provides composition and methods which use a selection of Envs, as gp120s, gp140s cleaved and uncleaved, gp145s, gp150s and gp160s, as proteins, as monomers or trimers, as DNAs, as RNAs, or any combination thereof, administered as primes and boosts to elicit immune response. See column 22, lines 18-23. These teachings indicate that nucleic acids encoding recombinant HIV-1 Env proteins can be formulated for immunization for any potential prime-boost strategies known in the art at the time of invention.
However, they are silent on administration schedule specified in claims 16 and 24-26.
It would have been prima facie obvious prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Kwong and the two Haynes references to arrive at the invention as claimed. One would have been motivated to do so to obtain a vaccination strategy using the modified HIV envelope polypeptides disclosed in the prior art references. As to the claimed prime and boost strategy, since the Haynes references disclose the claimed SEQ ID NOs: 192 and 193, one of skill in the art would have found it obvious to arrive at the claimed schedule through routine experimental optimization unless there is evidence that the claimed schedule is critical. Additionally, such a combination, or a substitution of one element for another known in the field to have the same function, is evidence that the claimed invention may be found obvious. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06. Therefore, the instant invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding claim 25, Haynes-2017 teaches that the recombinant HIV Env antigens may be administered in forms of liposome or nanoparticles, including ferritin nanoparticles. See claims 17-18.
Regarding claim 26, Haynes-2017 teaches that, in certain embodiments, the nucleic acids, for e.g. mRNAs encoding immunogens of the invention, are delivered by a lipid nanoparticle (LNP) technology. See column 23, lines 43-47.
Allowable Subject Matter
Sequences recited in claim 17 (i.e., SEQ ID NOs: 157-159 lacking the signal peptide sequences) are free of prior art.
Conclusion
No claims are allowed.
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/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671