DETAILED 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 Application/Amendment/Claims
This Office action is in response to the communications filed on January 23, 2026.
Currently, claims 1 and 4-20 are pending in the instant application. Claims 6-19 are withdrawn from further consideration as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 1, 4-5, and 20 are under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Response to Arguments
Applicant’s arguments filed on January 23, 2026 have been considered but are moot because they do not pertain to the new rejections necessitated by claim amendments as set forth hereinbelow.
New Objections/Rejections Necessitated by Amendment
Claim Objections
Claim 1 is objected to because of the following informalities: “linked linked” in line 6 should be “linked”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4-5, and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 4-5, and 20 recite “wherein the first, second and third nucleic acids are operably linked linked to regulatory sequences”. It is unclear whether a single combination of “regulatory sequences” (e.g., a combination of a promoter and an enhancer) link all three nucleic acids or whether each of the three nucleic acids is linked to separate regulatory sequences.
Claim 1 recites that the claimed method is performed “in a subject in need thereof”, and the claim also recites that the administered nucleic acids are expressed “in a mammalian cell.”
It is unclear whether the claimed method is meant to be amended to be an in vitro method performed in a mammalian cell because “a mammalian cell” reads on a cell that is in vitro. It is also unclear whether the broadly recited “mammalian cell” is within the “skin tissue” of the “subject in need thereof” or whether the “mammalian cell” is separate from the “subject in need thereof”.
For examination purpose, “a mammalian cell” will be interpreted as “the skin tissue of the subject in need thereof.”
Claim 20 recites that the method of claim 1 comprises transfecting a composition comprising “a nucleic acid” encoding SEQ ID NO:3. It is noted that claim 1 as currently amended recites three different nucleic acids (“a first nucleic acid”, “a second nucleic acid”, and “a third nucleic acid”) are included in the single composition. Hence, it is unclear which of the three (first, second, and third) nucleic acids is referred to by “a nucleic acid” of claim 20.
Claim 20 recites that “a nucleic acid” encoding SEQ ID NO:4. It is noted that claim 1 as currently amended recites three different nucleic acids (“a first nucleic acid”, “a second nucleic acid”, and “a third nucleic acid”) are included in the single composition. Hence, it is unclear which of the three (first, second, and third) nucleic acids is referred to by “a nucleic acid” of claim 20.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4-5, and 20 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. This includes a new matter rejection.
The instant claims are now amended to recite a method for inducing lymphangiogenesis in vivo in a subject in need thereof comprising transfecting skin tissue of the subject a composition comprising three different nucleic acids (Prox1, Pdpn, and SLP-76) that are operably linked to regulatory sequences for encoding gene products.
In the remarks filed on January 23, 2026, applicant did not point out the passages in the specification providing the written description support for the amended claims, nor does there appear to be a disclosure in the specification that supports and adequately describes the instantly claimed method that requires delivering a composition comprising three separate nucleic acids each operably linked to regulatory sequences to the skin tissue of a subject in need of inducement of lymphangiogenesis. Accordingly, the instantly claimed combination method is not adequately described in the manner to reasonably convey that the instant co-inventors had possession of the claimed subject matter as of the filing date sought in the instant case, and furthermore, the claims as currently amended introduce new matter that is not supported by the specification as originally filed.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4-5, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Alitalo et al. (US 2006/0025338 A1, of record; hereinafter Alitalo ‘338) in view of Poyet et al. (European Urology Supplements, 2012, 11(2):e906-e906a), Alitalo et al. (US 2006/0088532 A1; hereinafter Alitalo ‘532), and Gallego-Perez et al. (Nature Nanotechnology, 2017, 12:974-979, of record).
Alitalo ‘338 discloses a therapeutic method of improving lymphatic function in lymphatic cells thereof in a subject in need thereof comprising administering a “gene therapy construct” or a vector comprising “a Prox1 polynucleotide” of SEQ ID NO:34 encoding PROX1, which is a lymphatic endothelial marker, wherein “extensive sprouting of lymphatic capillaries occurs in the skin.” See paragraphs 0066, 0180, 0217, 0368, 0420, 0425,
It is noted that SEQ ID NO:34 of Alitalo ‘338 comprises a nucleotide sequence that encodes the 737 amino acids of SEQ ID NO:3.
Alitalo ‘338 teaches that the vector comprises “a suitable promoter and/or enhancer sequence” that is “operably linked to the polynucleotide”, wherein the promoter/enhancer “promotes the expression of the polynucleotide in a mammalian cell” in order “to facilitate the gene therapy.” See paragraphs 0046 and 0062.
Alitalo ‘338 does not teach further delivering PDPN and SLP76 via tissue nanotransfection.
Poyet teaches that PDPN, PROX-1, and SLP76 are “lymph-angiogenic genes” and that PDPN and PROX-1 play “a central role for lymphatic vessel development, migration potential” and SLP76 plays a role in lymphatic vessel maturation. See INTRODUCTION & OBJECTIVES.
Alitalo ‘532 teaches that podoplanin (PDPN) is an lymphatic endothelial cell (LEC)-specific marker and has an amino acid sequence of SEQ ID NO:65 encoded by the nucleotide sequence of SEQ ID NO:64. See paragraphs 0059 and 0175; Table 4.
It is noted that SEQ ID NO:65 of Alitalo ‘532 is identical to SEQ ID NO:4 claimed in the instant case.
Gallego-Perez teaches a method of delivering a therapeutic agent into the skin tissue via tissue nano-transfection (TNT) approach, which “can deliver cargo into the skin in a rapid (<1 s) and non-invasive/topical manner”, wherein the TNT approach can be used for “plasmid DNA” or other “gene modulation” applications. See pages 974 and 978.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the PROX1 gene therapy method of Alitalo ‘338 for improving lymphatic function in a subject in need thereof by further including PDPN and SLP76 sequences in the gene therapy vector/construct comprising promoters/enhancers operably linked to the three sequences. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to provide a greater level of induction of lymphangiogenesis in a subject by upregulating/overexpressing multiple “lymph-angiogenic genes” that play at multiple stages of lymphangiogenesis such as lymphatic vessel development, migration, and maturation rather than by upregulating only a single gene, PROX1, because PDPN, PROX-1, and SLP76 were art-recognized “lymph-angiogenic genes” that play central roles in lymphatic vessel development, migration potential, and maturation as reported by Poyet, and because one of ordinary skill in the relevant art would have reasonably deemed that upregulation of PDPN and SLP76 in addition to PROX1 of Alitalo ‘338 would induce lymphangiogenesis at a greater level or with more efficiency compared to the PROX1 gene therapy vector of Alitalo ‘338. It would have been obvious to one of ordinary skill in the art to include the nucleotide sequence of SEQ ID NO:34 of Alitalo ‘338 for encoding PROX1 amino acid sequence of SEQ ID NO:3 claimed in the instant case and the nucleotide sequence of SEQ ID NO:64 of Alitalo ‘532 encoding PDPN amino acid sequence of SEQ ID NO:4 claimed in the instant case because the sequences were already known and publicly available as evidenced by Alitalo ‘338 and Alitalo ‘532.
It would have been obvious to one of ordinary skill in the art before the effective filing date to deliver the gene therapy vector/construct comprising three different nucleotide sequences encoding PROX1, PDPN, and SLP76 that is rendered obvious above to the skin of the subject by utilizing Gallego-Perez’s TNT approach. One of ordinary skill in the art would have been motivated to select the skin tissue as the tissue containing lymphatic cells to which the combination gene therapy vector/construct is delivered with a reasonable expectation of success because the skin tissue known to be associated with lymphatic function as evidenced by Alitalo’s disclosure that “extensive sprouting of lymphatic capillaries occurs in the skin” thus one of ordinary skill in the art would have reasonably deemed that the method of improving lymphatic function in lymphatic cells reads on improving lymphatic function in the skin tissue. When delivering the combination gene therapy vector/construct to the skin tissue, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to utilize Gallego-Perez’s TNT approach in order to effectively, rapidly, and non-invasively deliver the three “lymph-angiogenic genes” to the skin tissue so as to improve the lymphatic function of the skin tissue in the subject in view of Gallego-Perez’s teachings pertaining to the benefits/advantages of using the TNT approach for expressing DNA for gene modulation applications.
Accordingly, claims 1, 4-5, and 20 taken as a whole would have been prima facie obvious before the effective filing date.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DANA H SHIN/Primary Examiner, Art Unit 1635