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 .
37 C.F.R. § 1.114
A request for continued examination under 37 C.F.R. § 1.114, including the fee set forth in 37 C.F.R. § 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 C.F.R. § 1.114, and the fee set forth in 37 C.F.R. § 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 C.F.R. § 1.114.
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 27 March, 2026. Claims 83-86, 88-90, 92-94, 96, and 100-102 are pending in the instant application. Claims 100-102 stand withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention. Claims 83-86, 88-90, 92-94, and 96 are currently under examination.
37 C.F.R. § 1.98
Applicants are reminded that the listing of references in the specification is not a proper information disclosure statement (e.g., see pp. 118-124). 37 C.F.R. § 1.98(b) requires a list of all patents, publications, applications, or other information submitted for consideration by the Office, and M.P.E.P. § 609.04(a), subsection I. states, “the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
37 C.F.R. § 1.821-1.825
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2) (e.g., see pages 88 and 102). In particular, page 88 discloses amino acid sequences for a CD33 leader sequence and IgG leader sequence and page 102 provides FC domain sequences. However, the disclosure failed to provide the appropriate sequence identifiers and these sequences do not appear to be in the sequence listing. Accordingly, this application fails to comply with the requirements of 37 C.F.R. § 1.821 through 1.825 for the reason(s) set forth below or on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures (PTO-2301). Applicants must provide a substitute computer readable form (CRF) copy of the "Sequence Listing", a substitute paper or compact disc copy of the "Sequence Listing", as well as an amendment directing its entry into the application. Applicants must also provide a statement that the content of the Sequence Listing information recorded in computer readable form is identical to the written (on paper or compact disc) sequence listing and, where applicable, includes no new matter, as required by 37 C.F.R. § 1.821(e), 1.82149, 1 821(g), 1.825(b), or 1.825(d). If applicant desires the sequence listing in the instant application to be identical with that of another application on file in the U.S. Patent and Trademark Office, such request in accordance with 37 C.F.R. § 1.821(e) may be submitted in lieu of a new CRF.
The sequence rules embrace all unbranched nucleotide sequences with ten or more bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 4 “specifically defined” nucleotides or amino acids. The rules apply to all sequences in a given application, whether claimed or not. All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database. See 37 C.F.R. § 1.821(a) and M.P.E.P. § 2421.02.
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.
Claims 83-86, 88-90, 92-94, and 96 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. 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.
Claims 83-85 reference the term HIV. This recitation is vague and indefinite because it is not readily manifest if the claims are directed toward HIV-1-specific T-cells, HIV-2-specific T-cells, or cross-reactive T-cells. The term HIV could potentially encompass human immunodeficiency virus type 1, 2, or both 1 and 2. However, HIV-1 and -2 are genotypically and phenotypically distinct lentiviruses (Franchini and Bosch, 1989). These viruses display different pathogenicities and geographical distributions. Moreover, these viruses only display 52%, 54%, and 35% amino acid sequence identity in Gag, Pol, and Env, respectively.
35 U.S.C. § 101
The following is a quotation of 35 U.S.C. § 101 which 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 therefore, 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.
Claims 83-86, 88-90, and 92-94 are 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). The claims are directed toward HIV antigen-specific T-cells expressing a broadly neutralizing antibody (bnAb). However, the specification clearly discusses the administration of the claimed cells to patients for the purpose of inducing a protective/therapeutic immune response against HIV. Thus, the term “cell” would clearly encompass cells within the subject. The scope of the claim, therefore, encompasses a human being, which is non-statutory subject matter. As such, the recitation of the limitation “isolated” or “purified” would be remedial. See 1077 O.G. 24, April 21, 1987.
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 83-86, 88-90, 92-94, and 96 stand 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 amended claims are broadly directed toward a cell comprising an expressible nucleic acid sequence encoding a polypeptide comprising an antibody or an antigen-binding fragment thereof, wherein the cell is a T-cell that recognizes HIV antigens, wherein the antibody or the antigen-binding fragment thereof comprises: (A-i) a light chain comprising a first secretory signal followed by a light chain variable region (VL) of an anti-human immunodeficiency virus-1 (HIV-1) broadly neutralizing antibody; and (A-ii) a heavy chain comprising a second secretory signal followed by a heavy chain variable region (VH) of said anti-HIV-1 broadly neutralizing antibody, wherein the VL and the VH are positioned non-contiguously and connected by at least one self-cleaving amino acid sequence, and wherein the VL and the VH binds to an epitope of the envelope protein of human immunodeficiency virus-1 (HIV-1), wherein the epitope is obtained from the group consisting of the CD4 binding site (CD4bs), V1/V2 glycan region, V3-glycan region, gp41 membrane proximal external region (MPER), and gp120/gp41 interface region (claim 83). Claim 84 further references cells obtained from an HIV-infected subject or an ex vivo expanded cell. Claim 85 further identifies the HIV antigens (e.g., Gag, Pol, and Nef) recognized by the T-cells of interest. Claims 88 further defines the CDRs present in the VH and VL regions (SEQ ID NOS.: 25-30, 56, 58, 60, 67, 69, 71) but fails to identify the FR regions. Claim 89 identifies the FR regions (55, 57, 59, 61, 66, 68, 70, and 72). The claims also reference 10-1074 VL and the VH amino acid sequences that display upwards of 30% amino acid sequence variation (claims 86, 89, and 92).
The disclosure suffers from a number of limitations. First, the disclosure fails to provide adequate guidance with respect to the genotype/phenotype of the claimed T-cells. The term T-cell encompasses a large genus of genotypically and phenotypically distinct cell types including CD4+ and CD8+ cells. There are various subsets of T-cells within each group (e.g., CD4+CD25-, CD4+CD25+, Qa-1-CD8+, CD8+CD28-, etc.) each with different functions. Moreover, CD4+ and CD8+ cells recognize different types of viral epitopes in the context of MHC class I or II. However, the claims fail to clearly set forth the genotypic/phenotypic properties of any given T-cell. Moreover, the disclosure fails to provide a representative number of species. Second, the disclosure encompasses and inordinate number of HIV T-cell epitopes. The broadest claims are not directed toward any specific CD4+ and CD8+ epitope. There are thousands of HIV-1 and -2 Th and CTL epitopes that have been identified in Gag, Pol, Env, Tat, Rev, Vif, Vpu, Vpx, and Nef. However, the disclosure fails to provide adequate support and direct the skilled artisan toward any particular HIV T-cell epitope. Third, the disclosure fails to provide adequate guidance with respect to the various antibody structures encompassed by the claim language. The broadest claims fail to identify any specific antibodies and their attendant VH and VL regions, as well as, their attendant CDRs and FR regions. The broadest claims also fail to identify the binding specificity of any given antibody. Additionally, the disclosure fails to support the claimed sequence variation. It has been well-documented that antigen binding interactions require contributions from both the VH and VL regions, including the CDRs and FRs (Sela-Culang et al., 2013). The disclosure fails to provide adequate guidance with respect to the structure and attendant properties of any given anti-HIV antibody.
Accordingly, when all the aforementioned factors are considered in toto, the skill artisan would reasonably conclude that Applicants were not in possession of a sufficient number of characterized T-cells and anti-HIV antibody molecules to support the claim breadth.
Applicants again argue that the invention is directed toward a long-term therapeutic approach to treating HIV infection using T-cell therapy, neutralizing antibody therapy, and antibody-dependent cellular cytotoxicity (ADCC). Applicants traverse and submit that a person of ordinary skill in the art (POSITA) would be able to identify T-cells that recognize different T-cell antigens as demonstrated by the methods set forth in the specification. Applicants further argue that a POSITA would be able to identify suitable antibody binding regions in the portions of the Env identified, as well as, broadly neutralizing antibodies (bnAbs) that bind to these regions. Accordingly, it was argued that sufficient guidance was provided. These arguments have been carefully considered but are not deemed to be persuasive. In order to practice the claimed invention and utilize it as a therapeutic, the skilled artisan would need to know the genotypic and phenotypic properties of the T-cell of interest, particularly with respect to the binding specificity and type of T-cell, as well as, the bnAb being expressed from said T-cell.
For some biomolecules, possession may be demonstrated by examples of identifying characteristics including a sequence, structure, binding affinity, binding specificity, molecular weight, and length. Although structural formulas provide a convenient method of demonstrating possession of specific molecules, other identifying characteristics or combinations of characteristics may demonstrate the requisite possession. However, the claimed invention itself must be adequately described in the written disclosure and/or the drawings. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 U.S.P.Q.2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 U.S.P.Q.2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
Other ways of establishing possession of a claimed invention may include unique cleavage by particular enzymes, isoelectric points of fragments, detailed restriction enzyme maps, a comparison of enzymatic activities, or antibody cross-reactivity. See Lockwood, 107 F.3d at 1572, 41 U.S.P.Q.2d at 1966 (Stating that the written description requirement may be satisfied by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that fully set forth the claimed invention."). Conversely, describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 U.S.P.Q.2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 U.S.P.Q.2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described.").
It is suggested the claims be amended to clearly identify the genotypic/phenotypic characteristics of the T-cell, as well as, the structure of the antibody being expressed from said T-cell. Applicants’ representative is invited to contact the Examiner to discuss suggested allowable claim language.
Enablement
Claims 83-86, 88-90, and 92-94 are rejected under 35 U.S.C. § 112(a), as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Applicants broadly claim a “cell” comprising an HIV antigen-specific T-cell expressing a broadly neutralizing anti-HIV antibody (bnAb). Giving the claims their broadest reasonable interpretation, the claims could also read on cells contained within a transgenic organism. The state of the art at the time of filing was such that the skilled artisan could not readily predict the phenotype of any given transgenic animal. Part of the unpredictability stems from the inability to control transgene integration into the target genome. Another critical element is that transgenic expression vectors must be designed on a case-by-case basis. Furthermore, even closely related species carrying the same transgene may exhibit broadly different phenotypes (Houdebine, 1994). Thus, at the time of filing, the phenotype of any given transgenic cell/animal was unpredictable.
Considering the lack of predictability in the art to which the invention pertains, the lack of guidance and direction provided by Applicants, and the absence of working examples, undue experimentation would be required to make and/or use the claimed invention. Amendment of the claim language to recite “isolated” or “purified” would obviate the rejection.
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.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 24 June, 2026
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