DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the first Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Status of the Claims
Claims 1-57, as filed on 17 September 2024, are pending.
Claim Objections
Claim 39 is objected to because of the following informality: in the last line of the claim, a comma is missing between “17” and “18.”
Claim 55 is objected to because of the following informality: in the last line of the claim, there is an extraneous comma immediately following “(HTLV-1).”
Appropriate corrections are required.
Claim Rejections - 35 U.S.C. 112(a)
The following is a quotation of 35 U.S.C. 112(a):
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.
Claims 53-57 are rejected under 35 U.S.C. 112(a) for lack of enablement.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics, 8 USPQ2d 1217 (Fed. Cir. 1988)). MPEP § 2164.01. Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. MPEP § 2164.01(a). These factors were outlined in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988) and include the following: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of any working examples; and (8) the quantity of experimentation necessary needed to practice the claimed invention based on the content of the disclosure. MPEP § 2164.01(a).
There is no requirement in claims 53-57 that an effective amount of the lipid particles (as defined in claim 1) or the composition incorporating them (as defined in claims 47 or 49) is administered to the cell or mammal. Applicant’s specification does not reasonably provide enablement for treating/preventing an infection or disease caused by HTLV-1, for inducing an immune response to HTLV-1, or for expressing gp46 or Tax antigens by administering a negligible or otherwise ineffective amount of the foregoing particles or composition to a cell or mammal. In sum, a person having ordinary skill in the art could not practice the full scope of Applicant’s invention, as recited in claims 53-57, without first engaging in undue experimentation.
Claim Rejections - 35 U.S.C. 112(d)
The following is a quotation of 35 U.S.C. 112(d):
[A] claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 48 and 50-52 are rejected under 35 U.S.C. 112(d) as being of improper dependent form.
Claim 52, for example, states as follows: “The composition of claim 49, wherein the composition is used for preventing the onset of and/or treating a disease caused by HTLV-1 selected from the group consisting of adult T cell leukemia/lymphoma (ATLL), HTLV-1 associated myelopathy (HAM) and HTLV-1 uveitis (HU), in an HTLV-1 infected person.” Emphasis added. The body of claim 52 is seemingly directed to a step of using the composition to prevent or treat various diseases caused by HTLV-1. That step, however, does further define the composition of claim 49. Thus, claim 52 does not further limit claim 49 and, consequently, fails to comply with 35 U.S.C. 112(d).
The foregoing rationale equally applies to claim 48 (“wherein the composition is used for expressing the gp46 antigen or Tax antigen”), claim 50 (“wherein the composition is used for inducing an immune response to human T-cell leukemia virus type 1”), and claim 51 (“wherein the composition is used for preventing and/or treating infection with human T-cell leukemia virus type 1”). Emphasis added.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Claim Rejections - 35 U.S.C. 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 1-30, 34, 36-38, and 41-57 are rejected under 35 U.S.C. 103 as being unpatentable over the following combination: Bancel (US 2015/0141499 A1), Reyes (US 5,066,579), Matsuoka (JP 2016032439 A), Kabiri (US 2018/0099042 A1), Koizumi (US 9,803,199 B2) and, optionally, Ciaramella (US 2018/0296662 A1).
Bancel is directed to engineered nucleic acids and methods of use thereof. Title.
Bancel teaches: “Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to kill or reduce the growth of viruses. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent viral infection, or to improve a subject’s heath or wellbeing.” Abstract.
Bancel teaches that mRNA can be engineered to encode an anti-viral polypeptide that has therapeutic effect against human T-cell leukemia virus 1 (HTLV-1). Paras. [0036]-[0037]; see also page 27 at claim 12. The foregoing mRNA can be administered to humans to treat a viral infection caused by HTLV-1. Page 27 at claims 15-17.
Reyes is directed to an HTLV-1 peptide antigen and assay. Title.
Reyes teaches a recombinant peptide antigen derived from HTLV-1 protein gp46. Column 2, lines 27-38; column 11 at lines 7-47; column 13 at claim 1; see also Figures 1A-1C.
Reyes teaches that the recombinant gp46 peptide antigen can be formulated in a pharmaceutically acceptable adjuvant and administered as a vaccine to immunize an individual against T-cell leukemia. Column 2, lines 53-58; see also Abstract.
Matsuoka, which published in Japanese, is directed to a vaccine for the prophylaxis and/or therapy of human T-cell leukemia virus type 1 (HTLV-1) related disease. Abstract. The examiner obtained an English machine translation of Matsuoka using Google Patents. Unless otherwise indicated, all citations refer to that translation, which accompanies this Office action.
Matsuoka teaches that the wild-type Tax protein (WT-Tax) or the mutant protein WT-Tax-M22 can be formulated in a vaccine and administered to prevent or treat various HTLV-1-related diseases. Pages 2/8, 4/8, and 6/8; see also page 1/6 at claims 6-7. The examiner notes that the amino acid sequences for both WT-Tax and WT-Tax-M22 are taught in Figure 1A of Matsuoka.
Matsuoka teaches that “[t]he present invention also relates to a polynucleotide encoding the peptide of the present invention.” (Emphasis added) Page 3/8; see also page 1/8 at claim 9.
Matsuoka teaches: “The vaccine of the present invention can be mixed with a physiologically acceptable carrier, excipient, diluent or the like, and can be administered orally or parenterally as a pharmaceutical composition.” (Emphasis added) Page 4/8.
Kabiri is directed to chimeric peptides against HTLV-1. Title.
Kabiri teaches that a chimeric peptide comprising both Tax and gp46 can be employed for immunization against HTLV-1. Abstract; see also Figure 2B.
Koizumi is directed to a cationic lipid that forms a lipid particle. Title/Abstract.
Koizumi teaches: “[T]he present inventors have completed the present invention by finding a novel cationic lipid and further finding a nucleic acid lipid particle comprising the novel cationic lipid that can encapsulate therein a nucleic acid molecule, can be used at a low concentration, and permits a high level of delivery into cells.” Column 1, line 66, to column 2, line 5 (emphasis added).
Koizumi teaches: The term “nucleic acid” includes a messenger RNA (mRNA). Column 65, lines 5-8. “The nucleic acid contained in the nucleic acid lipid particle can be any single-stranded RNA without particular limitations and also includes mRNA that is translated into a protein.” (Emphasis added) Column 92, lines 25-28.
Koizumi teaches: “The single-stranded RNA is used for treating a disease or supplying a beneficiary protein. The single-stranded RNA is delivered to an organ responsible for the disease through the nucleic acid lipid particle of the present invention and further transported into the cytoplasm. When the single stranded RNA encodes a protein, the single-stranded RNA is translated into the protein in the cytoplasm so that this protein brings about the curing of the disease.” (Emphasis added) Column 93, lines 27-35.
Claim 1 of Koizumi is reproduced below:
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The examiner notes that the cationic lipid set forth in claim 1 of Koizumi matches the cationic lipid set forth in claim 9 of the present application.
Additionally, the exemplary cationic lipid taught in Formula 4 of Kiozumi (columns 7-8), which is set forth below, matches the cationic lipid set forth in claim 10 of the present application.
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Similarly, the exemplary cationic lipid taught in Formula 11 of Kiozumi (columns 9-10), which is set forth below, matches the cationic lipid set forth in claim 10 of the present application.
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The foregoing teachings support the examiner’s conclusion that (i) lipid particles comprising the cationic lipids recited in the claims of the present application are disclosed in the prior art as being especially suitable for delivering mRNA into cells (Koizumi); (ii) the prior art discloses that gp46 peptides and/or Tax peptides can be administered in a vaccine formulation to treat or prevent HTLV-1-related diseases (Reyes, Matsuoka, Kabiri); (iii) the prior art suggests that mRNA can be engineered to encode gp46 and/or Tax peptides and, thereafter, included in a lipid particle-based vaccine against HTLV-1 (Bancel, Matsuoka, Kabiri); and (iv) the combination of (i), (ii), and (iii) would have yielded nothing more than predictable results to one of ordinary skill in the art. MPEP § 2143(I)(A) (combining prior art elements according to known methods to yield predictable results), citing KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) and Sakraida v. AG Pro, Inc., 425 U.S. 273, 282 (1976). Therefore, claims 1-11, 46-52, and 54-56 are prima facie obvious.
The optional reference (Ciaramella) provides relevant foundational guidance on how to formulate cationic lipid particles for mRNA delivery, as discussed below in relation to claims 12-30:
Regarding claims 12-17, Applicant is referred to Ciaramella at paragraphs [0062] and [0075]. Ciaramella further discloses that the non-cationic lipid can be a neutral lipid, such as DSPC (distearoyl phosphatidylcholine), DPPC, POPC, DOPE (dioleoyl phosphatidylethanolamine), and SM (sphingomyelin). Paras. [0305], [0307], and [0334]. The examiner notes that the neutral lipid of Ciaramella corresponds to the “amphipathic lipid” of the present claims.
Regarding claims 18-19, Applicant is referred to paragraph [0302] of Ciaramella.
Regarding claims 20-27, Applicant is referred to Ciaramella at paragraph [0307]. MPEP § 2144.05(I) (“In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”). Additionally, Applicant is alerted that “‘[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’” MPEP § 2144.05(II)(A), quoting In re Aller, 220 F.2d 454, 456 (CCPA 1955). Again, the neutral lipid of Ciaramella corresponds to the “amphipathic lipid” of the present claims.
Regarding claims 28-30, Ciaramella discloses: “In some embodiments, the ratio of lipid to RNA (e.g., mRNA) in lipid nanoparticles may be 5:1 to 20:1, 10:1 to 25:1, 15:1 to 30:1 and/or at least 30:1.” Para. [0302]. Applicant is referred to MPEP § 2144.05(I) (quoted above).
Regarding claim 34, Applicant is referred to Matsuoka at page 4/8 (bottom), which teaches the TL130/131AS Tax mutation that is often referred to as Tax-M22. See also Figure 1A (showing the amino acid sequence of Tax-M22).
Regarding claims 36 and 37, the optional reference (Ciaramella) teaches that “[s]ignal peptides, comprising the N-terminal 15-60 amino acids of proteins, are typically needed for the translocation across the membrane on the secretory pathway and, thus, universally control the entry of most proteins both in eukaryotes and prokaryotes to the secretory pathway.” Para. [0215]. Ciaramella additionally teaches: “In some embodiments, the signal peptide fused to the antigenic polypeptide is an artificial signal peptide. In some embodiments, an artificial signal peptide fused to the antigenic polypeptide encoded by the RNA (e.g., mRNA) vaccine is obtained from an immunoglobulin protein, e.g., an IgE signal peptide or an IgG signal peptide. In some embodiments, a signal peptide fused to the antigenic polypeptide encoded by a RNA (e.g., mRNA) vaccine is an Ig heavy chain epsilon-1 signal peptide (IgE HC SP) having the sequence of: MDWTWILFLVAAATRVHS.” Para. [0218].
Regarding claim 38, Applicant is referred to paragraphs [0188] and [0293] of Ciaramella.
Regarding claims 41-44, Applicant is referred to Bancel at paragraphs [0058]-[0064] and to Ciaramella at claims 36-39.
Regarding claim 45, Ciaramella discloses: “In some embodiments, a nanoparticle (e.g., a lipid nanoparticle) has a mean diameter of 10-500 nm, 20-400 nm, 30-300 nm, 40-200 nm. In some embodiments, a nanoparticle (e.g., a lipid nanoparticle) has a mean diameter of 50-150 nm, 50-200 nm, 80-100 nm or 80-200 nm.” Para. [0325]. Applicant is referred to MPEP § 2144.05(I) (quoted above).
Regarding claim 53, Applicant is referred Matsuoka at pages 5/8 and 6/8. Applicant is additionally referred to paragraph [0278] of Ciaramella, which discloses: “The STD RNA (e.g., mRNA) vaccines may be induced for translation of a polypeptide (e.g., antigen or immunogen) in a cell, tissue or organism. In some embodiments, such translation occurs in vivo, although such translation may occur ex vivo, in culture or in vitro.”
Regarding claim 57, Applicant is referred Matsuoka at page 4/8, which states: “The HTLV-1-related disease to be treated and / or prevented is not particularly limited as long as it is a disease caused by HTLV-1. For example, adult T cell leukemia (ATL), HTLV-1-related myelopathy (HAM), HTLV-1-related myelopathy, HTLV-1 uveitis, HTLV-1-related bronchitis, HTLV-1-related Sjogren's syndrome, HTLV-1-related myositis, HTLV-1-related infectious dermatitis and the like. Among these, ATL is preferable from the viewpoint that the therapeutic and / or prophylactic effect can be more reliably exhibited.” See also page 1/8 at claim 9.
Claims 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Bancel (US 2015/0141499 A1), Reyes (US 5,066,579), Matsuoka (JP 2016032439 A), Kabiri (US 2018/0099042 A1), Koizumi (US 9,803,199 B2) and, optionally, Ciaramella (US 2018/0296662 A1), as applied above to claims 1-30, 34, 36-38 and 41-57, in view of Mirsaliotis (“Conformation-specific antibodies targeting the trimer-of-hairpins motif of the human T-cell leukemia virus type 1 transmembrane glycoprotein.” Journal of virology 81.11 (2007): 6019-6031) and Meier (“Foldon, the natural trimerization domain of T4 fibritin, dissociates into a monomeric A-state form containing a stable β-hairpin.” Journal of molecular biology 344.4 (2004): 1051-1069).
The combination of references applied to claim 1 is silent as to whether the gp46 antigen includes an oligomerization domain. Consequently, those references do not satisfy claims 31-33. As explained below, the following two references compensate for this deficiency: Mirsaliotis and Meier.
Mirsaliotis teaches: “HTLV-1 primarily infects CD4+ T cells in vivo. Infection is initiated by the action of the viral envelope glycoproteins, which are expressed on the surface of the virus or infected cell as a trimer of the gp46 surface glycoproteins (SU) attached to a trimer of the gp21 transmembrane glycoprotein.” (Emphasis added) Page 6019.
Meier teaches: “The C-terminal domain of T4 fibritin (foldon) is obligatory for the formation of the fibritin trimer structure and can be used as an artificial trimerization domain.” (Emphasis added) Abstract.
Before the effective filing date of the claimed invention, the foregoing teachings of Mirsaliotis and Meier would have motivated a person having ordinary skill in the art to include a fibritin (foldon) domain in the gp46 antigen to force the protein into its biologically relevant, highly stable trimeric state, which is most likely to trigger the desired anti-HTLV-1 immune response in the host. Unfolded or monomeric gp46 might expose internal, non-protective decoy epitopes. The foldon-induced trimer ensures that only the appropriate, surface-exposed structures are presented to the host’s immune system. In sum, claims 31-33 are prima facie obvious.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Bancel (US 2015/0141499 A1), Reyes (US 5,066,579), Matsuoka (JP 2016032439 A), Kabiri (US 2018/0099042 A1), Koizumi (US 9,803,199 B2) and, optionally, Ciaramella (US 2018/0296662 A1), as applied above to claims 1-30, 34, 36-38 and 41-57, in view of Robek (“Immortalization of CD4+ and CD8+ T lymphocytes by human T-cell leukemia virus type 1 Tax mutants expressed in a functional molecular clone.” Journal of virology 73.6 (1999): 4856-4865) and Macaire (“Tax Protein-induced Expression of Antiapoptotic Bfl-1 Protein Contributes to Survival of Human T-cell Leukemia Virus Type 1 (HTLV-1)-infected T-cells.” Journal of Biological Chemistry 287.25 (2012): 21357-21370).
The combination of references applied to claims 1 and 34 teaches the Tax-M22 mutant, which has both the T130A and the L131S mutations (see Matsuoka at bottom of page 4/8). However, that combination is silent regarding the two additional mutations required by claim 35, which are L319R and L320S. As explained below, the following two references compensate for this deficiency: Robek and Macaire.
Robek teaches: “[I]t is likely that Tax disregulates the cell cycle through many different mechanisms, leading to the eventual immortalization and transformation of the infected cell.” (Emphasis added) Page 4856, left column.
Robek teaches: “In addition to activating transcription from the viral long terminal repeat (LTR) through the cyclic AMP response element binding protein/activating transcription factor (CREB/ATF) family of transcription factors, Tax activates the expression of multiple cellular promoters through the NF-kB pathway of transcriptional activation. The Tax mutants M22 and M47 have previously been demonstrated to selectively abrogate the ability of Tax to activate transcription through the NF-kB or CREB/ATF pathway, respectively.” (Emphasis added) Abstract.
In Figure 1 (page 4857), Robek teaches that the Tax-M47 mutant has both the L319R and L320S mutations.
Additionally, Figure 1 of Robek echoes the teaching in Matsuoka that the Tax-M22 mutant has the T130A and the L131S mutations.
Macaire confirms the specific mutations in Tax-M22 and Tax-M47, as shown in Figure 3A (page 21362) reproduced below:
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Before the effective filing date of the claimed invention, the foregoing teachings of Robek and Macaire would have motivated a person having ordinary skill in the art to include in the lipid particle HTLV-1 vaccine an mRNA encoding a gp46 protein that combines the mutations of Tax-M22 and Tax-M47, in an effort to further mitigate the dangerous oncogenic risks of wild-type Tax while preserving its high immunogenicity. Therefore, claim 35 is prima facie obvious.
Allowable Subject Matter
Claim 40 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Referring to claim 40, SEQ ID NO: 20 is both novel and non-obvious. SEQ ID NO: 17 of Revaud (US 9,987,351), which is representative of the closest prior art, has a sequence similarity of 49.9%.
In the interest of compact prosecution, the examiner notes that claim 39 is similarly allowable, provided Applicant overcomes the objection based on the informality set forth near the beginning of this Office action.
Referring to claim 39, SEQ ID NO: 17 is novel and non-obvious. SEQ ID NO: 12 of Matano (US 2020/0155669 A1), which is representative of the closest prior art, has a sequence similarity of 67.8%.
Referring to claim 39, SEQ ID NO: 18 is novel and non-obvious. SEQ ID NO: 12 of Matano (US 2020/0155669), which is representative of the closest prior art, has a sequence similarity of 63.1%.
Additional detail is set forth in the Automated Biotechnology Sequence Search (ABSS) search results dated 8/24/2026, which have been included in the electronic file history of this application and are accessible via Patent Center.
Applicant is encouraged to focus claim 1 on the allowable subject matter identified above.
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Conclusion
Claims 1-38 and 41-57 are rejected.
Claims 39-40 and 55 are objected to.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER ANTHOPOLOS whose telephone number is 571-270-5989. The examiner can normally be reached on Monday – Friday (9:00 am – 5:00 pm). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany P. Barham, can be reached on Monday – Friday (9:00 am – 5:00 pm) at 571-272-6175. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./
05 September 2026
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
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