Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 22 April, 2026. Claims 1, 5, 9, 12, 23, 31, 41, 48-50, 52, 65, 68, 72, 74-76, 78, 84, and 99 are pending in the instant application. Applicants’ election of Group I (claims 1, 5, 9, 12, 23, and 31) without traverse is noted. Claims 41, 48-50, 52, 65, 68, 72, 74-76, 78, 84, and 99 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention.
37 C.F.R. § 1.98
The information disclosure statement filed 12 September, 2023, has been placed in the application file and the information referred to therein has been considered.
37 C.F.R. § 1.84
The drawings filed 22 June, 2023, have been reviewed and are acceptable. The petition filed under 37 C.F.R. § 1.84(a)(2) to accept color photographs and/or drawings has been granted.
35 U.S.C. § 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.
Claim 12 is 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. Two separate requirements are set forth under this statute: (1) the claims must set forth the subject matter that applicants regard as their invention; and (2) the claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant.
The claim references a neutralizing antibody that binds to the isolated HIV-1 Env polypeptide with an affinity of “about 30 µM or less”. This recitation is vague and indefinite because the upper and lower limits of binding affinity cannot be readily ascertained. Moreover, the specification fails to provide a detailed definition of this term or a standard for ascertaining the requisite degree. Accordingly, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Amendment of the claim language to reference a neutralizing antibody that binds with an affinity of 30 µM or less to the polypeptide of interest would be acceptable.
35 U.S.C. § 112(a)
The following is a quotation 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.
Written Description
Claims 1, 5, 9, 12, 23, and 31 are rejected under 35 U.S.C. § 112(a), 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, at the time the application was filed, had possession of the claimed invention. Amgen, Inc. v. Sanofi, 872 F.3d 1367, 124 U.S.P.Q.2d 1354 (Fed. Cir. 2017). AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 111 U.S.P.Q.2d 1780 (Fed. Cir. 2014). Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 920, 69 U.S.P.Q.2d 1886, (Fed. Cir. 2004). Enzo Biochem, Inc. v. Gen-Probe, Inc., 296 F.3d 1316, 63 U.S.P.Q.2d 1609, (Fed. Cir. 2002). Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 U.S.P.Q.2d 1398, (Fed. Cir. 1997). Fiers v. Revel Co., 984 F.2d 1164, 25 U.S.P.Q.2d 1601, (Fed. Cir. 1993). Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016, (Fed. Cir. 1991). In re Rasmussen, 650 F.2d 1212, 211 U.S.P.Q. 323 (C.C.P.A. 1981). In re Wertheim, 541 F.2d 257, 191 U.S.P.Q. 90 (C.C.P.A. 1976).
The crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. In re Kaslow, 707 F.2d 1366, 1375, 217 U.S.P.Q. 1089, 1096 (Fed. Cir. 1983). In re Wilder, 736 F.2d 1516, 1520 222 U.S.P.Q. 349, 372 (Fed. Cir. 1984, cert. denied, 469 U.S. 1209 (1985). Texas Instruments, Inc. v. International Trade Comm’n, 871 F.2d 1054, 1063, 10 U.S.P.Q.2d 1257, 1263 (Fed. Cir. 1989). Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. In re Wertheim, 541 F.2d 257, 263, 191 U.S.P.Q. 90, 97 (C.C.P.A. 1976). In re Driscoll, 562 F.2d 1245, 1250, 195 U.S.P.Q. 434, 438 (C.C.P.A. 1977). It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations. Martin v. Mayer, 823 F2d 500, 505, 3 U.S.P.Q.2d 1333, 1337 (Fed. Cir. 1987).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor has possession of the claimed invention. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996).
Determination of adequate written description requires the Examiner to read and analyze the specification for compliance with 35 U.S.C. § 112(a). In particular, each claim should be analyzed to determine its broadest reasonable interpretation consistent with written description. Each claim should be evaluated to determine if sufficient structures, acts, or functions are recited to make clear the scope and meaning of the claim, including the weight to be given the preamble. The entire application should be reviewed including the specific embodiments, figures, and sequence listings, to understand how applicant provides support for the various features of the claimed invention. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated that the inventor was in possession of the claimed invention. Such a review is conducted from the standpoint of one of ordinary skill in the art at the time the application was filed (see, e.g., Wang Labs., Inc. v. Toshiba Corp., 993 F.2d 858, 865, 26 USPQ2d 1767, 1774 (Fed. Cir. 1993)) and should include a determination of the field of the invention and the level of skill and knowledge in the art. Finally, the Examiner should determine whether there is sufficient written description to inform a skilled artisan that the inventor was in possession of the claimed invention as a whole at the time of filing.
The claims are broadly directed toward an isolated HIV-1 Env polypeptide comprising an amino acid sequence that is at least 90% identical to SEQ ID NO.: 119, wherein the polypeptide further comprises mutations at D279, V430, D460, T461, T462, D463, and N464, wherein said numbering is based upon the prototypic isolate HIV-1 HXB2 (SEQ ID NO.: 268). Claims 23 and 31 also reference amino acid sequences that are at least 90% identical to SEQ ID NOS.: 120, 121, 129, and 130. SEQ ID NO.: 119 corresponds to the 426c.TM4 HIV-1 gp120 immunogen (353 aa). SEQ ID NOS.: 120 and 121 correspond to IGT2 SOSIP and IGT1 SOSIP immunogens (each 626 aa). SEQ ID NOS.: 129 and 130 correspond to IGT2 SOSIP Spy Tag and IGT1 SOSIP Spy Tag immunogens (each 655 aa).
At just 10% amino acid sequence variation, the claims encompass an inordinate number of HIV-1 polypeptide species. For example, substituting any one of the naturally-occurring amino acids in 426c.TM4 HIV-1 gp120 (SEQ ID NO.: 19) would encompass upwards of ~4 x 1095 Env variants. Examining the IGT2 SOSIP HIV-1 Env (SEQ ID NO.: 129), the claimed sequence variation would encompass upwards of ~1 x 10139 Env variants.1 The purpose of the modifications in the isolated HIV-1 Env polypeptides is to produce Env immunogens that are capable of inducing broadly neutralizing germline antibodies (bNAbs) of the IOMA class that recognize the CD4-binding site (CD4bs). However, it has been well-documented in the prior art that generating HIV-1 Env immunogens that are capable of inducing germline bNAbs has been challenging (Xiao et al., 2009; Hoot et al., 2013; Gristick et al., 2023). A major impediment to HIV-1 vaccine design is that most inferred germline (iGL) precursors of known bNAbs do not bind with detectable affinity to native Envs on circulating HIV-1 strains. Germline-targeting approaches involving potential HIV-1 Env immunogens requires potential immunogens to bind to bNAb precursors during in vivo immunization. However, these types of bnAbs are difficult to elicit because of the utilization of rare light chain (LC) complementarity-determining region 3 (CDRL3) loops and the many somatic hypermutations (SHMs) required to accommodate the highly conserved N267gp120 glycan.
Perusal of the specification provided a limited number of HIV-1 Env variants that are capable of inducing IOMA-like bNAb responses. In particular, only two HIV-1 Env immunogens were identified with the recited properties, IGT1 gp120 and IGT2 gp120. These immunogens contain specific mutations at the amino acids corresponding to D279, V430, D460, T461, T462, D463, and N464. However, the specification fails to identify any additional HIV-1 Env variants with the desired properties. The specification also fails to provide any illumination on the influence of adjacent and distal amino acids in the Env on immunogenicity. Thus, the specification clearly fails to describe the generation and characterization of a reasonable number of HIV-1 Env species that would reasonably be expected to induce CD4bs bNAbs.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that Applicants were not in possession of a sufficient number of HIV-1 Env immunogens to support the claim breadth currently sought.
35 U.S.C. § 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)(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, 12, 23, and 31 are rejected under 35 U.S.C. § 102(a) (2) as being clearly anticipated by Stamatatos et al. (U.S. Pat. No. 11,883,485 B2, published 30 January, 2024, and claiming priority to Prov. Appl. No. 62/724,555, filed 29 August, 2018; hereinafter referred to as “Stamatatos et al. (2024)”). The claims are directed toward an isolated HIV-1 Env polypeptide immunogen that shares at least 90% amino acid sequence identity with the 426c.TM4 HIV-1 gp120 immunogen (SEQ ID NO.: 119) and comprises a mutation at one of D279, V430, D460, T461, D463, or N464, wherein said numbering is based on the prototypic isolate HIV-1 BHX2 (SEQ ID NO.: 268). The claims additionally reference sequences that display at least 90% amino acid sequence identity with IGT1 SOSIP gp120/IGT2 SOSIP gp120 (SEQ ID NOS.: 121/122) and IGT1 SOSIP SPY TAG gp120/IGT2 SOSIP SPY TAG gp120 (SEQ ID NOS.: 130/129) (claims 23 and 31, respectively). Another claim limitation simply stipulates that the HIV-1 Env immunogen is capable of binding to a bNAb with an affinity of about 30 µM or less (claim 12). This property is inherent to the HIV-1 Env immunogen sequence.
Stamatatos et al. (2024) provide HIV-1 Env 426c gp120 immunogens that share at least 90% amino acid sequence similarity with the claimed immunogens. In particular, SEQ ID NO. 175 (426c gp120) is nearly identical to SEQ ID NO.: 119 (see Appendix A) and SEQ ID NO. 177 (426c SOSIP BG505) is nearly identical to SEQ ID NOS.: 121, 120, 130, and 129 (see Appendix B). The 426c gp120 immunogen displays greater than 98% amino acid sequence relatedness and contains D460N and D463N mutations. The 426c SOSIP immunogen also displays greater than 98% amino acid sequence relatedness and contains D460N and D463N mutations. This teaching clearly meets all of the claimed limitations.
Allowable Subject Matter
The individual HIV-1 Env immunogens set forth in SEQ ID NOS.: 118 and 117 (IGT1 gp120 and IGT2 gp120, respectively) appear to be free of the prior art. Amendment of the claim language to encompass HIV-1 Env immunogens consisting of these sequences would be acceptable.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
Information regarding the status of an application may be obtained from the Patent Center. Status information for published applications may be obtained from the Patent Center. Status information for unpublished applications is available through the Patent Center for authorized users only. Should you have questions about access to Patent Center, 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.
Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 27 July, 2026
Appendix A
11,883,485 (17/269,199) SEQ 175 (v SEQ 119) 426c core W/O SS; lacks a HIS tag; D460N and D463N mutations
OTHER INFORMATION: 426c core-gp120 without signal sequence
Query Match 96.5%; Score 1862; Length 347; Best Local Similarity 98.8%; Matches 343; Conservative 2; Mismatches 2; Indels 0; Gaps 0;
Qy 1 VWKEAKTTLFCASDAKAYEKECHNVWATHACVPTDPNPQEVVLENVTENFNMWKNDMVDQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 VWKEAKTTLFCASDAKAYEKECHNVWATHACVPTDPNPQEVVLENVTENFNMWKNDMVDQ 60
Qy 61 MQEDVISIWDQCLKPCVKLTNTSTLTQACPKVTFDPIPIHYCAPAGYAILKCNNKTFNGK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 MQEDVISIWDQCLKPCVKLTNTSTLTQACPKVTFDPIPIHYCAPAGYAILKCNNKTFNGK 120
Qy 121 GPCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIVIRSKNLRDNAKIIIVQLNKSVEIVC 180
||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||
Db 121 GPCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIVIRSKNLSDNAKIIIVQLNKSVEIVC 180
Qy 181 TRPNNGGSGSGGDIRQAYCNISGRNWSEAVNQVKKKLKEHFPHKNISFQSSSGGDLEITT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TRPNNGGSGSGGDIRQAYCNISGRNWSEAVNQVKKKLKEHFPHKNISFQSSSGGDLEITT 240
Qy 241 HSFNCGGEFFYCNTSGLFNDTISNATIMLPCRIKQIINMWQEVGKAIYAPPIKGNITCKS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 HSFNCGGEFFYCNTSGLFNDTISNATIMLPCRIKQIINMWQEVGKAIYAPPIKGNITCKS 300
Qy 301 DITGLLLLRDGGDTTDNTEIFRPSGGDMRDNWRSELYKYKVVEIKPL 347
||||||||||||:||:||||||| |||||||||||||||||||||||
Db 301 DITGLLLLRDGGNTTNNTEIFRPGGGDMRDNWRSELYKYKVVEIKPL 347
Appendix B
11,883,485 (17/269,199) SEQ 177 (v SEQ 120) 4426c BG505 SOSIP;
OTHER INFORMATION: 426c:BG505_WT-Sosip without signal sequence
Query Match 98.3%; Score 3290; Length 625; Best Local Similarity 98.7%; Matches 616; Conservative 1; Mismatches 7; Indels 0; Gaps 0;
Qy 3 NLWVTVYYGVPVWKEAKTTLFCASDAKAYEKEVHNVWATHACVPTDPNPQEVVLENVTEN 62
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 NLWVTVYYGVPVWKEAKTTLFCASDAKAYEKEVHNVWATHACVPTDPNPQEVVLENVTEN 61
Qy 63 FNMWKNDMVDQMQEDVISIWDQSLKPCVKLTPLCVTLNCTNVNVTSNSTNVNSSSTDNTT 122
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 FNMWKNDMVDQMQEDVISIWDQSLKPCVKLTPLCVTLNCTNVNVTSNSTNVNSSSTDNTT 121
Qy 123 LGEIKNCSFDITTEIRDKTRKEYALFYRLDIVPLDNSSNPNSSNTYRLINCNTSTCTQAC 182
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 LGEIKNCSFDITTEIRDKTRKEYALFYRLDIVPLDNSSNPNSSNTYRLINCNTSTCTQAC 181
Qy 183 PKVTFDPIPIHYCAPAGYAILKCNNKTFNGKGPCNNVSTVQCTHGIKPVVSTQLLLNGSL 242
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 182 PKVTFDPIPIHYCAPAGYAILKCNNKTFNGKGPCNNVSTVQCTHGIKPVVSTQLLLNGSL 241
Qy 243 AEEEIVIRSKNLRNNAKIIIVQLNKSVEIVCTRPNNNTRRSIRIGPGQTFYATDIIGDIR 302
|||||||||||| :||||||||||||||||||||||||||||||||||||||||||||||
Db 242 AEEEIVIRSKNLSDNAKIIIVQLNKSVEIVCTRPNNNTRRSIRIGPGQTFYATDIIGDIR 301
Qy 303 QAYCNISGRNWSEAVNQVKKKLKEHFPHKNISFQSSSGGDLEITTHSFNCGGEFFYCNTS 362
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 302 QAYCNISGRNWSEAVNQVKKKLKEHFPHKNISFQSSSGGDLEITTHSFNCGGEFFYCNTS 361
Qy 363 GLFNDTISNATIMLPCRIKQIINMWQEPGKCIYAPPIKGNITCKSDITGLLLLRDGGNAL 422
||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Db 362 GLFNDTISNATIMLPCRIKQIINMWQEVGKCIYAPPIKGNITCKSDITGLLLLRDGGNTT 421
Qy 423 RPTEIFRPSGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVFL 482
|||||| |||||||||||||||||||||||||||||||||||||||||||||||||||
Db 422 NNTEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVFL 481
Qy 483 GFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEAQQHLLKLTVWGIKQLQARV 542
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 482 GFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEAQQHLLKLTVWGIKQLQARV 541
Qy 543 LAVERYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQ 602
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 542 LAVERYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQ 601
Qy 603 IIYGLLEESQNQQEKNEQDLLALD 626
||||||||||||||||||||||||
Db 602 IIYGLLEESQNQQEKNEQDLLALD 625
1 These calculations were performed as follows: TV=(NY)(X!)/(Y!)((X-Y-1)!), wherein, TV=the total number of variant sequences, N=the number of amino acids or nucleotides that can be substituted (i.e., if any of the 20 naturally occurring amino acids can be substituted, N=19; if any of the four naturally occurring nucleotides can be substituted, N=3), Y=the number of amino acids/nucleotides in the parent sequence that can be substituted (i.e., if the amino acid sequence is 100 aa in length and 10% genetic variation is allowed, Y=10 [100@10%]), and X=the total sequence length of the sequence of interest.
Prosecution Insights