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 Nov. 13, 2025. Claims 1, 3-7, 9-15 and 17-21 are pending and currently examined.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(Previous Rejection – Withdrawn) Claims 1-15 and 17-21 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly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 pre-AIA the applicant regards as the invention.
This rejection is withdrawn in view of the amendments as well as Applicant’s clarifications filed on Nov. 13, 2025.
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.
(Previous Rejection – Maintained) Claims 1, 3-7, 9-15 and 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (Advanced Drug Delivery Reviews 64 (2012) 1547–1568) and Chang et al. (US 2016/0175408 A1, published on Jun. 23, 2016), in view of Henderson (US 2017 /0196966 A1, published on Jul. 13, 2017), and further in view of Yu et al. (Microbes Infect. 2020 Mar;22(2):74-79. Epub 2020 Feb 1).
The base claim 1 is amended to specify that the immunizing composition comprises an immunologically effective amount of i) a polypeptide, or ii) a nucleic acid encoding the polypeptide, wherein the polypeptide comprises a polypeptide at least 95% identical to amino acids 330 to 521 of SEQ ID NO: 4; and that the administering comprises a repeated motion of penetrating the microneedle delivery device into the subject.
Kim reviews the technology of microneedles for drug and vaccine delivery. It teaches that microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin, that shown in more than 350 papers published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, bio-therapeutics and vaccines, including published human studies with a number of small molecule and protein drugs and vaccines, and that Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. See e.g. Abstract and Figure 2. Kim teaches that vaccination using microneedles is especially appealing because it not only offers expected advantages that simplify vaccine distribution and improve patient compliance, but also enable vaccine targeting to the skin. It is already known that the skin offers immunologic advantages over conventional intramuscular injection, but until now there have not been simple, reliable methods to vaccinate in the skin. Microneedles—both solid microneedle patches and hollow microneedles for intradermal injection—address this limitation and can make skin vaccination a practical clinical reality. Motivated by these opportunities, vaccine delivery has been the most widely investigated use of microneedles. See e.g. Section 3.1.3.
Chang teaches an invention relating to microneedle delivery technology with unique compositions and formulations. See e.g. Abstract. Chang teaches that each microneedle will have one or multiple grooves inset along its outer wall. This structural feature of the dermal delivery device allows liquids stored in a reservoir at the base of each needle to travel along the needle shaft into the tissue. Altogether, this innovation is a functional treatment regimen applicator that enables the optimal restorative efficacy of bioactive formulations delivered beneath the surface of the skin. See e.g. [0455]. Chang teaches that with a microneedle system designed to deliver liquid compositions to the dermal and subcuticular layers of the skin, a broad range of therapeutic objectives can be met. This includes but is not limited to the administration of vaccines, vitamins, minerals, biologics, organic or inorganic drugs, and anesthetics. See e.g. [0456].
Chang teaches that provided therein is a system that presents additional advantage conferring elements specific to the controlled delivery of many types of treatment solutions above that of existing microneedle platforms that facilitate the direct application of bioactive formulations transdermally. “Due to a microneedle design that facilitates liquid flow along the outside of the needle, our direct applicator system does not suffer from the issue of clogging that hollow microneedle systems do. Furthermore, consistent delivery depth of treatment is achieved over a topical application after microneedling. This in turn, allows for the patient-specific delivery of kinetic enhancing, nutritional, anesthetic or medicinal agents to the skin, in accordance with practitioner-determined concentrations. With a pressure activated release of liquid formulations our system is easily used through a repeated motion delivery to the skin.” See [0457].
Chang further teaches that applying bioactive formulations comprises only penetrating within the dermal layer, or at a dermal and epidermal junction of the skin with repeated motions on the skin. See [0062].
In summary, teachings of Kim and Chang indicate that the microneedle technology and its application in vaccine delivery to skin of a subject is known in the art at the time of invention and is considered to be advantageous over conventional intramuscular injection. Chang specifically teaches the microneedle delivery device as claimed and its specific advantages. However, Kim and Chang do not teach or suggest the application of the microneedle delivery technology in the administration of a SARS-CoV-2 vaccine.
Henderson teaches an invention relating to microneedle devices being used in delivering viral vaccines, such as a vaccine comprising a recombinant alphavirus replicon encoding an exogenous polypeptide, wherein the recombinant alphavirus replicon is coated onto or embedded into a plurality of microneedles. See e.g. Abstract. It teaches that a variety of suitable viruses (e.g., RNA viruses) are available (for vaccines involving the microneedle delivery), including, but not limited to, picornavirus, flavivirus, coronavirus, pestivirus, rubivirus, calcivirus, and hepacivirus. See e.g. [0060]. Therefore, teachings of Henderson indicate that it has been at least contemplated by a skilled artisan to apply a microneedle device in delivery of a coronavirus vaccine.
Yu presents a review on advances in research and development of fast diagnosis methods, as well as potential prophylactics and therapeutics to prevent or treat 2019-nCoV (SARS-Cov-2) infection. It teaches that, as the major vaccine target, the S protein has been evaluated in different types of vaccines against infection by CoVs [29]. Apart from the inactive whole virus particle [30], live attenuated virus with gene deletion [31] , four more vaccines which mainly contain S protein were studied. These include a virus-like particle which incorporated S protein into hepatitis virus or influenza virus protein [32,33]; virus vectors, such as modified vaccinia virus Ankara (MVA) or Adenovirus carrying S protein [34,35]; S protein subunit vaccine, like RBD-based protein [29,36]; and DNA vaccine which encodes the full length or part of the S protein gene [37,38]. See page 75, right column, para 3.
Yu teaches that most CoVs share a similar viral structure, similar infection pathway, and a similar structure of the S proteins [41], suggesting that similar research strategies should also be applicable for the 2019-nCoV. For example, the study of MERS-CoV vaccines was accelerated by virtue of strategies that had been established for SARS-CoV [42]. It has been reported that the 2019-nCoV is also genetically close to SARS-CoV [43,44]. Therefore, to predict whether vaccines developed for SARS-CoV will also be effective against 2019-nCoV infection, the full-length S protein sequences from the 2019-nCoV, a SARS-CoV, and two genetically similar bat CoV strains were selected for alignment (Fig.1). The results indicated more than 50% homology of the viruses. However, the most variable residues are located in S1 (included in RBD and RBM), a critical vaccine target, implying that neutralizing antibodies that were so effective against SARS-CoV infection may fail to recognize the 2019-nCoV, and that multiple amino acid differences at the receptor binding motif may modify virus tropism, a possible reason for cross-species transmission. See page 75, right column, para 4. Fig. 1 of Yu presents comparison of S protein sequences of coronaviruses, including that of SARS-CoV-2 (2019-nCoV), which comprises SEQ ID NO: 4.
Accordingly, teachings of Yu provide detailed guidance on various strategies for SARS-CoV-2 vaccine development, including the suggestion for using the spike protein, especially the S1 region, which comprises SEQ ID NO: 4, as vaccine target.
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to combine the teachings of Kim, Chang, Henderson and Yu to arrive at the invention as claimed. One would have been motivated to do so, e.g., to develop a SARS-CoV-2 vaccine based a microneedle delivery system disclosed in Chang that has the advantages of a microneedle delivery system in general and advantages of a specific microneedle delivery system as disclosed in Chang. There is a reasonable expectation of success based on the abundance of information available at the time of invention on coronavirus vaccine development, molecular biology of SARS-CoV-2 and a plethora of experience in the application of microneedle devices in vaccine development.
Regarding claims 9-10, Chang teaches that with a pressure activated release of liquid formulations the system is easily used through a repeated motion delivery to the skin (see e.g. [0457]), it would have been prima facie obvious for one of ordinary skill in the art to arrive at the claimed administration requirements through routine optimization unless the claimed requirements produce unexpected results.
Regarding claim 11, the cited references are silent on proximity of injection sites to lymph nodes. However, since skins of various body sites can be selected as injection sites, one of skills in the art would have found it obvious to optimize the immunization efficacy through routine experimentation, including experimentation of injection sites which may or may not be in “proximity” to a lymph node (note, lymph nodes are widely spread over body areas, many routinely used vaccine injection site, e.g. shoulder, can be considered as proximity to a lymph node.
Regarding claim 12, Chang teaches that it should be understood that further embodiments developed for use with non-hollow or hollow microneedle systems of delivery by those skilled in the art fall within the spirit and scope of that disclosure. See [0474].
Regarding claims 13-15 and 17-19, see teachings of Chang at e.g. [0475] and [0486]-[0488].
Regarding claim 20, it would have been obvious for one of ordinary skill in the art at the time of invention to self-administer a vaccine as claimed when desired.
Double Patenting Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
(Previous Rejection – Maintained) Claims 1, 3-7, 9-15 and 17-21 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-12 of US Patent 11202753.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass a method generating an immune response in a subject comprising administering to the subject’s skin an immunizing composition derived from SARS-CoV-2 with a microneedle device. The difference is that, while the patented claims require that wherein the polypeptide comprises amino acids 330 to 521 of SEQ ID NO : 4, the instant claims require that the polypeptide comprises a sequence at least 95% identical to amino acids 330-521 of SEQ ID NO: 4).
The patented claims anticipate the instant claims 1, 3-7, 9-15 and 17-20.
Regarding claim 21, this rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Response to Applicant’s Arguments
Applicant’s arguments filed on Nov. 13, 2025 have been fully considered. Arguments regarding withdrawn rejections are moot. Applicant’s arguments relevant to the current rejections are addressed as follows.
To the 103 rejection under Kim, Chang, Henderson and Yu, Applicant argues that Kim, alone or in combination with other cited art would not have prompted the skilled artisan to arrive at the claimed methods, let alone having a reasonable expectation of achieving success. Applicant argues that Kim opines that delivery with a microneedle patch is envisioned as an alternative to hypodermic injection that is less painful, safer, and simpler for patients to self administer, that the claimed microneedle device delivers the composition into the subject’s skin using a repeated motion of penetrating the microneedle delivery device into the subject’s skin, which is not how a microneedle patch delivers a composition to the subject. Applicant argues that Henderson recites a huge laundry list of possible molecules and none of which are polypeptides or nucleic acids as claimed, that Chang is more geared towards aesthetic treatments for the skin, vaccination is mentioned as one of many possible treatment, but no vaccines are exemplified in Chang, and that there is no teaching or suggestion in Yu that a specific fragment comprising amino acids 330 to 521 of SEQ ID NO: 4 identified by Applicant would be effective at inducing an immune response.
Applicant’s arguments are not persuasive. As indicated in the rejection body above, teachings of Kim and Chang indicate that the microneedle technology and its application in vaccine delivery to skin of a subject is known in the art at the time of invention and is considered to be advantageous over conventional intramuscular injection. Chang specifically teaches the microneedle delivery device as claimed and that such as microneedle delivery devices can be used to deliver various different biological compositions, including vaccines, to the skin of a subject. Chang explicitly teaches that administering by the disclosed microneedle delivery device can comprise repeated motion of penetrating the microneedle device into the subject’s skin. Teachings of Henderson indicate that it has been at least contemplated by a skilled artisan to apply a microneedle device in delivery of a coronavirus vaccine, providing a nexus between a microneedle device and vaccination against coronaviruses, which include SARS-CoV-2. Teachings of Yu provide detailed guidance on various strategies for SARS-CoV-2 vaccine development, including the suggestion for using the spike protein, especially the S1 region, which comprises SEQ ID NO: 4, as vaccine antigen. Therefore, a skilled artisan would have found it obvious to combine the teachings of Kim, Chang, Henderson and Yu to arrive at the invention as claimed.
As to Applicant’s argument that there would not have a reasonable expectation of achieving success with the teaching of Kim (and as well as those of Chang, Henderson and Yu), Applicant does not elaborate what is considered as a “success”. A clinically successful vaccine might not be readily expected based on the teachings of Kim and Chang for microneedle-based vaccines, one of skill in the art would have readily expected that the microneedle devices of Kim and Chang would be effective in delivery of vaccine antigen to a subject’s skin to induce expected immune responses, which is a function for the microneedle devices taught in Kim and Chang.
As to Applicant’s argument that there is no teaching or suggestion in Yu that a specific fragment comprising amino acids 330 to 521 of SEQ ID NO: 4 identified by Applicant would be effective at inducing an immune response, the examiner does not agree. By reciting “wherein the polypeptide comprises a polypeptide at least 95% identical to amino acids 330 to 521 of SEQ ID NO:4”, the claims are not limited to a specific fragment comprising amino acids 330 to 521 of SEQ ID NO: 4, it is open to any polypeptide comprising a sequence that is at least 95% identical to aa 330 to 521 of SEQ ID NO: 4, which represents a region in the spike protein of SARS-CoV-2.
To the double patenting rejection, Applicant requests holding the rejection in abeyance, pending the determination of allowable subject matter. This rejection is, therefore, maintained.
Conclusion
No claims are allowed.
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 extension fee 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 NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JANET ANDRES, on (571) 272-0867, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/Primary Examiner, Art Unit 1671