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 .
Applicant’s preliminary amendment to the claims dated 3/7/25 has been entered.
Claims 1-13, 15, 17-21 and 24 are examined on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) 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.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-13, 15, 17-21 and 24 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.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice .... reduction to drawings .... or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1-13, 15, 17-21 and 24 are rejected as lacking adequate descriptive support for a using a functional fragment of the claimed S1 or a protein with at least 90% or 95% identity to SEQ ID NO:s 3, 4, 9, 21 or 22 and a functional fragment of a LTB protein or a protein with at least 90% or 95% identity to SEQ ID NO: 15.
The claimed invention is drawn to a method of producing a protective response to Porcine Epidemic Diarrhea Virus (PEDV) in an animal, the method comprising,
a) orally administering to said animal a composition comprising plant or plant product comprising a S1-LTB fusion protein, wherein said S1-LTB fusion protein comprises the Spike (S1) protein of PEDV operably fused to the heat labile enterotoxin B subunit (LTB) peptide, wherein said S1 protein comprises a sequence having at least 90% or at least 95% identity to SEQ ID NO: 3, 4, 9, 21 or 22 or a functional fragment of said S1 protein; and wherein said LTB peptide comprises a sequence having at least 90% or at least 95% identity to SEQ ID NO: 15 or a functional fragment of said LTB peptide.
The claimed invention also requires a functional fragment of SEQ ID NO:s 3, 4, 9, 21 or 22.
In support of the claimed genus (functional fragments of S1 and LTB protein and proteins with at least 90% or 95% identity to the claimed sequences for the S1 and LTB protein), the application discloses one example in which PDK, which comprises the S1 protein of SEQ ID NO: 4 is linked to the LTB protein of SEQ ID NO: 15 exhibits elevated IgA antibody production based on the data presented in Figure 7. No derivatives or variants or mutants thereof within the scope of functional fragments of S1 or LTB protein or proteins having at least 90% or 95% identity to SEQ ID NO: 3, 4, 9, 21 or 22 and SEQ ID NO: 15 are disclosed that can achieve this induction of protective responses to PEDV in an animal or producing a greater mucosal immune response to PEDV. Thus, the application fails to provide examples of a representative species of the claimed genus.
Further, while the claims provide both a structure and a function, the application fails to draw any correlation between the two. I.e., there is no evidence that any functional fragments of S1 or the claimed sequences of S1 and LTB of SEQ ID NO: 15 can still retain the function of induction of protective responses to PEDV in an animal or producing a greater mucosal immune response to PEDV. Moreover, no correlation has been made to which portion of the S1 and LTB protein would meet the requirement of functional fragments in order to achieve the claimed induction of protective responses to PEDV in an animal or producing a greater mucosal immune response to PEDV. Lastly, the specification does not establish a representative number of species. The teachings of the art also fail to indicate that, without such evidence, those in the art would have expected the full scope of the claimed functional fragments of the S1 protein and LTB protein would confer the claimed induction of protective responses to PEDV in an animal or producing a greater mucosal immune response to PEDV. For example, a search of the art indicates that the S1 protein of PEDV possess more than one function (see Sun et al. (Veterinary Microbiology, 2008, Vol. 131, pages 73-81)), which teach “The S protein, a glycoprotein peplomer on the viral surface, plays an important role in induction of neutralizing antibodies, specific receptor binding and cell membrane fusion” [see left column of page 74] and a functional fragment of said LTB protein has more than one function based on the teachings of Salmond et al. (Infection and Immunity, 2004, Vol. 72, No. 10, pages 5850-5857), which teach that LTB protein mediates receptor interaction and up take of the toxin by target cells” and “recombinant preparations of EtxB act as immunomodulatory proteins capable of suppressing Th1-associated inflammatory processes in vivo”. [see left column of page 5850]
Thus, in view of the above, there would have been significant uncertainty as to which functional fragments of S1 or LTB protein or proteins having at least 90% or 95% identity to SEQ ID NO: 3, 4, 9, 21 or 22 and SEQ ID NO: 15 are disclosed that can achieve this induction of protective responses to PEDV in an animal or producing a greater mucosal immune response to PEDV. In view of this uncertainty and the lack of any examples of the claimed genus, the claims are rejected for lack of adequate written description support.
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.
Claims 1-13, 15, 17-21 and 24 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, 7 and 15 recite, “a functional fragment of said S1 protein”, however, Sun et al. (Veterinary Microbiology, 2008, Vol. 131, pages 73-81) teach that the S1 protein of PEDV possess more than one function, “The S protein, a glycoprotein peplomer on the viral surface, plays an important role in induction of neutralizing antibodies, specific receptor binding and cell membrane fusion”. [see left column of page 74] Therefore, it is unclear which function claims 1, 7 and 15 is referring to with regard to the functional fragment of the S1 protein.
Claims 1 and 7 recite, “functional fragment of said LTB protein”, however, based on the teachings of Salmond et al. (Infection and Immunity, 2004, Vol. 72, No. 10, pages 5850-5857) teach that subunit B possesses at least two functions “mediates receptor interaction and up take of the toxin by target cells” and “recombinant preparations of EtxB act as immunomodulatory proteins capable of suppressing Th1-associated inflammatory processes in vivo”. [see left column of page 5850] Therefore, it is unclear which function claims 1 and 7 is referring to with regard to the functional fragment of the LTB protein.
Claims 2-13, 17-21 and 24 are also rejected because they depend from claims 1 or 7 or 15, but do not remedy these deficiencies.
Claim 3 recites the limitation "said vaccine" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 6 and 9 recite, “said composition comprising said S1-LTB fusion protein comprises a higher ratio of high molecular weight S1 protein to low molecular weight S1 protein in comparison to a composition comprising said S1 protein without said LTB peptide operably fused thereto.” However, it is unclear what the metes and bounds of “higher ratio” are in comparison to a composition comprising said S1 protein lacking the LTB protein. Furthermore, it is unclear what the boundaries of “higher ratio” and “high molecular weight” and “low molecular weight” are since the claims nor the specification clarify these generic limitations.
Claim Rejections - 35 USC § 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-12, 13, 15, 17-21 and 24 are rejected under 35 U.S.C. 102a1 as being anticipated by Howard et al. (US PGPub 2020/0080101).
The claimed invention is drawn to a method of producing a protective response to Porcine Epidemic Diarrhea Virus (PEDV) in an animal or producing a greater mucosal immune response to PEDV in an animal, the method comprising,
a) orally administering to said animal a composition comprising plant or plant product comprising a S1-LTB fusion protein, wherein said S1-LTB fusion protein comprises the Spike (S1) protein of PEDV operably fused to the heat labile enterotoxin B subunit (LTB) peptide, wherein said S1 protein comprises SEQ ID NO: 3, wherein said LTB peptide comprises SEQ ID NO: 15; and
b) producing a protective response to said PEDV in said animal; or
b) producing a mucosal immune response to said PEDV in said animal, wherein said mucosal immune response in said animal is greater in comparison to an animal that has been administered a composition comprising said S1 protein without said LTB peptide operably fused thereto.
The protective response comprises a serum antibody response in said animal and is at least 20 times greater than serum antibody response in an animal not administered said vaccine
The composition comprising the S1-LTB fusion protein elicits a greater mucosal immune response than a composition comprising said S1 protein without said LTB peptide operably fused thereto and the greater levels of fecal anti-PEDV IgA in said animal.
The composition comprising the S1-LTB fusion protein comprises a higher ratio of high molecular weight S1 protein to low molecular weight S1 protein in comparison to a composition comprising said S1 protein without said LTB peptide operably fused thereto.
Milk of said animal comprises said S1-LTB fusion protein, the composition comprises plant material or plant tissue or seed or embryo of seed. The animal is a pig.
The S1-LTB fusion protein further comprises at least one of the COE peptide of SEQ ID NO: 12 and the DC3 peptide of SEQ ID NO: 13 operably fused thereto. 19.
The plant or plant product comprises a construct comprising a nucleic acid molecule encoding said S1-LTB fusion protein operably linked to: a) a promoter preferentially directing expression to seed tissue of a plant; and b) a nucleic acid molecule targeting expression of said S1-LTB fusion protein in the endoplasmic reticulum of said plant. The construct comprises two copies of the nucleic acid molecule encoding that S1-LTB fusion protein. The S1 protein is encoded by SEQ ID NO: 1, 2 or 25 or a sequence with at least 90% or 95% identity to these sequences. The LTB protein is encoded by a nucleotide sequence comprising SEQ ID NO: 14 or a sequence having at least 90% or 95% identity to SEQ ID NO: 14.
Howard et al. teach the generation of a fusion protein comprising the S1 protein of PEDV, which is fused to a heat labile enterotoxin B (LTB). [see paragraph 135 and figure 1] One example of the S1 protein is SEQ ID NO: 3 of Howard et al., which is identical to SEQ ID NO: 3 of the instant invention and an example of the LTB is that of SEQ ID NO: 15 of Howard et al. and it is identical to SEQ ID NO: 15 of the instant invention. Howard et al. also teach the nucleotide sequences of SEQ ID NO:s 1 and 14, which are identical to that of SEQ ID NO:s 1 and 14 of the instant invention. Howard et al. further teach that the S1 protein of SEQ ID NO: 12 or 13 can be used in their fusion protein. They also teach that the fusion protein can be administered to pigs in order to induce a protective immune response that achieves a serum antibody response at least 20 times greater than the serum antibody response in an animal not being vaccinated. [see claims 1-3] The fusion protein is part of a composition that comprises plant material, plant tissue, seed or embryo of seed. [see claims 5-6] Howard et al. also teach that fecal samples of vaccinated pigs tested positive for antibodies (IgA) specific for the S1 protein. [see paragraphs 102, 125 and 133] It is also taught by Howard et al. that a plant product containing a construct comprising nucleic acid comprising, (a) a promoter preferentially directing expression to seed tissue of a plant; (b) a nucleic acid molecule encoding a S1 polypeptide of said PEDV comprising SEQ ID NO: 3, 4 or 9 or a sequence having at least 90% identity to SEQ ID NO: 3, 4, 9, 21 or 22 or a functional fragment operably linked to said promoter; and (c) a nucleic acid molecule targeting expression of said polypeptide in the endoplasmic reticulum of said plant; and expressing said S1 polypeptide in said plant at levels of at least 1 mg/kg of seed of said plant;
wherein said construct further comprises a sequence selected from a sequence encoding the COE peptide of SEQ ID NO: 12, a sequence encoding the LTB heat labile peptide of SEQ ID NO: 15 or the DC3 peptide of SEQ ID NO: 13 a or a combination thereof;
wherein said construct comprises two copies of said nucleic acid molecule encoding a S1 polypeptide;
wherein said construct comprises two copies of a nucleic acid molecule selected from sequence encoding the COE peptide of SEQ ID NO: 12, a sequence encoding the LTB heat labile peptide of SEQ ID NO: 15 or the DC3 peptide of SEQ ID NO: 13 and a sequence encoding an endoplasmic reticulum retaining sequence or a combination thereof. [see claims 7-10]
With regard to the greater immune responses generated against the S1-LTB compared to only the S1 protein (instant claims 4 and 8), the active steps taught by Howard et al. are the same as presently claimed using the same fusion protein as presently claimed. Therefore, their method would inherently achieve a greater immune response (see MPEP 2112.02 I-“PROCESS CLAIMS — PRIOR ART DEVICE ANTICIPATES A CLAIMED PROCESS IF THE DEVICE CARRIES OUT THE PROCESS DURING NORMAL OPERATION”).
With regard to the composition comprising said S1-LTB fusion protein comprises a higher ratio of high molecular weight S1 protein to low molecular weight S1 protein in comparison to a composition comprising said S1 protein without said LTB peptide operably fused thereto, Howard et al. teach formulating a composition that comprises the S1-LTB fusion protein, which would inherently possess a higher ratio the high molecular weight S1 protein since it would lack the S1 protein not possessing the LTB fused (see MPEP 2112.01 “II. COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES”).
Therefore, the teachings of Howard et al. anticipate the instant invention.
Double Patenting
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12, 13, 15, 17-21 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,566,255 in view of Howard et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented invention requires a composition comprising a construct containing neucleic acid sequences that encode the presently claimed fusion protein with the same S1 protein amino acid sequences and LTB sequences and also including the same COE or DC3 sequences. The patented invention also requires administering the S1 protein to an animal with a plant or plant product comprising the S1 protein, as claimed in the instant invention, but the method of claims 1-5 of ‘255 do not require the fusion of the LTB protein (SEQ ID NO: 15) to the S1 protein. Howard et al. however do teach administering the instantly claimed fusion protein to an animal (pig). (see teachings of Howard et al. summarized above) Therefore, the patented invention in view of the teachings of Howard et al. render obvious the instant invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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, Michael Allen can be reached at (571) 270-3497. 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.
/BENJAMIN P BLUMEL/ Primary Examiner, Art Unit 1671
Prosecution Insights