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 .
Response to Amendment
Applicant’s remarks and amendments to the claims received 05/05/2026 have been acknowledged. Claim 1 has been amended. Claim14 has been cancelled.
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, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 8, and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Fukuda (Fukuda, Satoshi, et al. "Preparation and characterization of anti-fumonisin monoclonal antibodies." Bioscience, biotechnology, and biochemistry 58.4 (1994): 765-767, of record), hereinafter Fukuda, in view of Yang et al (Yang, Changwon, Gwonhwa Song, and Whasun Lim. "Effects of mycotoxin-contaminated feed on farm animals." Journal of Hazardous Materials 389 (2020): 122087, of record), hereinafter Yang, as evidenced by Jensen et al (Jensen, FC et al. "Adjuvant activity of incomplete Freund's adjuvant." Advanced drug delivery reviews vol. 32,3 (1998): 173-186. doi: 10.1016/s0169-409x(98)00009-x, of record) hereinafter Jensen.
Fukuda teaches the generation of antibodies against fumonisin B1 (FB1) via the immunization of animals with conjugated-FUM. Here, FBI was conjugated, using glutaraldehyde, with ovalbumin (OVA) or keyhole limpet hemocyanin (KLH) for use as an immunogen (FBI- OVA and FBI-KLH). The first injection consisted of 100 uL of conjugate in PBS and the same volume of Freund's complete adjuvant - a water-in-oil emulsion. The second injection (day 15) consisted of 100 uL each of conjugate in PBS and Freund's incomplete adjuvant (Abstract and Page 765). Freund's complete and incomplete adjuvants are water-in-oil emulsion adjuvants used for vaccine delivery as evidenced by Jensen (Jensen et al, see Abstract and 1st para. of Introduction). Per the instant claims, the minimal steps required for protecting an animal against fumonisin (FUM)- induced mycotoxicosis is administering conjugated FUM to the animal. As such, the methods disclosed by Fukuda would necessarily be capable of protecting an animal against fumonisin (FUM)-induced mycotoxicosis. It is noted that the primary "wherein" clause recited in claim 2- "wherein the method protects the animal against one or more clinical signs of FUM-induced mycotoxicosis"-merely states the intended result of the claimed method and thus does not provide patentable distinctiveness to the claimed methods. The only positive limitation in the claim is the administering step; and the courts have held that a " whereby [or, in this case, wherein] clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.") (quoting Minton V. Nat'l Ass'n ofSecurities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) (see MPEP 2111.04). Further, the term "vaccine" in the preamble of claim 14 is the intended use of the composition, but does not result in any structural difference between the claimed invention and the prior art. As such, a composition comprising an adjuvant and a pharmaceutically acceptable carrier (in this case, Freund's complete/incomplete adjuvant, PBS, and conjugated-FUM) is suitable as a vaccine. Lastly, per the instant claims, the KLH and OVA are proteins having a molecular mass above 10.000 Da.
Fukuda does not specifically teach that the animal administered conjugated FUM is swine or chicken.
However, Yang teaches that mycotoxins such as fumonisins are secondary products produced by fungi in cereals and are frequently found in the livestock industry as contaminants in farm animal feed. Exposure to mycotoxins can cause immunotoxicity and impair reproductive function in farm animals. In addition, exposure of tissues, such as the kidneys, liver, and intestines, to mycotoxins can exert histopathological changes that can interfere with animal growth and survival. Pigs and poultry are the most susceptible and sensitive farm animals to the effects of mycotoxins. For example, fumonisin B1 (FB1) is reported to cause porcine pulmonary edema. Moreover, when exposed to pigs, FB1 is associated with the development of disorders such as pulmonary edema and liver failure. FB1 causes pig intestinal disorders by increasing the level of free sphingolipid bases and reducing the number of glycolipids in the plasma membrane. Moreover, FB1 causes a reduction in feed intake, egg production, and body weight in poultry, while also causing disorders such as hepatic necrosis and thymic cortical atrophy (see Abstract and Section: 3.3. Effects of fumonisins on farm animals and Figure 1).
It would have been obvious to artisans to administer conjugated FUM to swine and chickens. One of ordinary skill in the art would have been motivated to do so since pigs and chickens are particularly susceptible to the detrimental health effects of mycotoxins such as fumonisin B1 as taught by Yang, and conjugated FUM can be used to immunize animals can against fumonisin as taught by Fukuda, and thus offer protection against FUM-induced mycotoxicosis. Therefore, one of ordinary skill in the art would reasonably expect that immunization of swine and chickens against fumonisin comprising administering conjugated FUM to said animals can protect these animals against FUM-induced mycotoxicosis.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Fukuda, as applied to claims 1-3, 8, and 15-19 above, and further in view of Skountzou et al (US20170100477A1, of record), hereinafter Skountzou.
The teachings of Fukuda in view of Yang have been discussed above and differ from the instantly claimed invention in that it is not specifically taught that the conjugated FUM vaccine is administered to an animal intradermally, orally, and/or intramuscularly.
However, Skountzou teaches that that immunogenic compositions comprising an antigen or vaccine and an adjuvant can be delivered to a subject by several routes of administration, including mucosal (e.g. oral) or parenteral (e.g. intradermal or intramuscular) (Abstract, Para. 0031, Para. 0077), wherein the subject is any animal (Para. 0037).
It would have been obvious to one of ordinary skill in the art to modify the method of immunizing animals with conjugated-FUM disclosed by Fukuda such that the conjugated-FUM is administered orally, intradermally, or intramuscularly. One of ordinary of skill in the art would have been motivated to do so since immunization of animals with an antigen/vaccine and adjuvant can occur by several routes of administration, including orally, intradermally, intramuscularly as taught by Skountzou. Therefore, one of ordinary skill in the art would reasonably expect that oral, intradermal, or intramuscular administration of conjugated-FUM to an animal can effectively protect the animal against FUM-induced mycotoxicosis.
Claims 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Fukuda, as applied to claims 1-3, 8, and 15-19 above, and further in view of Emery et al (US5906826A), hereinafter Emery.
The teachings of Fukuda have been discussed above and differ from the instantly claimed invention in that it is not specifically taught that the conjugated FUM is administered to an animal
at an age of 6 weeks or younger, 4 weeks or younger, or 1-3 weeks of age.
However, Emery teaches a method of priming an immune response in the presence of maternal antibodies in a young animal over an extended time so that the animal will produce a secondary active immune response substantially immediately upon contact with the immunogen when passive protection is no longer provided by circulating maternal antibodies, the method comprising administering to a 1-90-day old animal an immunogenic agent (see Abstract and Col. 2, Ln. 29-40), wherein the immunogenic agent can be derived from fungi and/or is a toxin (Col. 2, Ln. 58-67; and Col. 5, Ln. 46-48). A young animal that is 1-90 days old encompasses those that are 6 weeks or younger, 4 weeks or younger, and 1-3 weeks of age per the instant claims.
It would have been obvious to one of ordinary skill in the art to modify the method of immunizing an animal with conjugate-FUM disclosed by Fukuda such that the animal is a young animal that is 1-90 days old. One of ordinary skill in the art would have been motivated to do so in order to prime an immune response in the young animal such that the animal will produce a secondary active immune response upon contact with the immunogen when passive protection is no longer provided by circulating maternal antibodies as taught by Emery. Therefore, one of ordinary skill in the art would reasonably expect that administration of conjugated-FUM to a young animal 1-90-days old can effectively protect the animal against FUM-induced mycotoxicosis.
Response to Arguments
Applicant's arguments filed 05/05/2026 have been fully considered but they are not persuasive.
With respect to rejections under 35 USC 103, Applicant argues that there is no teaching or suggestion in Fukuda that vaccination confers protection against FUM-induced mycotoxicosis. While raising antibodies in mice per se may be routine, Applicant states that inducing protection against a corresponding disease is not and that protection must be demonstrated by challenge. For example, Applicant states that while raising robust antibody responses to HIV is simple, developing a protective HIV vaccine has proven elusive over 40 years of intensive research, underscoring the unpredictability of achieving protection even when antibody responses are robust and that inducing an antibody response to an antigen does not translate to protective immunity to that antigen. As such, Applicant asserts that vaccine development is not predictable without testing whether the vaccine provides protection upon challenge.
Further, Applicant artisans would not have a reasonable expectation of success that administering conjugated FUM would protect swine or chickens against FUM-induced mycotoxicosis, as required by amended claim 1; and to assert otherwise would be based on impermissible hindsight gleaned from the instant application. Additionally, Applicant argues that there is no showing in the prior art that conjugated FUM protected mice, or any other animal, against FUM-induced mycotoxicosis. This long absence of success further underscores the lack of a reasonable expectation of success and highlights the surprising nature of the claimed protection.
Lastly, Applicant argues that even if one were to modify Fukuda to use swine or chickens as discussed in Yang, given the unpredictability of generating effective vaccines, there would not be a reasonable expectation of success of achieving the claimed method of protecting a swine or a chicken against FUM-induced mycotoxicosis, as required by the claims. Thus, Applicant contends that Yang and other secondary references do not cure the deficiencies of Fukuda discussed above.
In response to Applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this case, Fukuda teaches the same active step of administering conjugated fumonisin (FUM) to an animal to elicit an immune response against fumonisin. Yang further teaches that fumonisin B1 can cause immunotoxicity and impair reproductive function in farm animals, particularly pigs and poultry, thereby providing motivation to administer conjugated-FUM to those animals. In view of these teachings, artisans would have reasonably expected that administration of conjugated-FUM to swine or chickens would protect against FUM-induced mycotoxicosis contrary to Applicant’s assertion. The reasonable expectation of success requirement refers to “the likelihood of success” in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016). Further, conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) (“To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’”); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) (“This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness.” (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that “the expectation of success need only be reasonable, not absolute”)). Therefore, the prior art need not expressly demonstrate that immunization with conjugated-FUM protects against FUM-induced mycotoxicosis. Instead, the conclusion of reasonable expectation of success is based on the combined teachings of the cited references, namely that administration of conjugated toxin elicits antibodies against fumonisin B1 and that fumonisin B1 is a causative agent of mycotoxicosis in swine and poultry (MPEP 2143.02).
While Applicant has demonstrated that conjugated-FUM provides protection against mycotoxicosis, these data alone do not establish that the observed protection would have been “surprising” relative to teachings of the prior art. Applicant has not provided objective evidence demonstrating that the claimed method achieves results that are unexpectedly superior to those that would have been reasonably expected from combined teachings of the prior art (see MPEP 716.02). Moreover, the experimental data provided in the specification performed using specific conditions cannot be extrapolated to the generic method claimed with the expectation that any alleged unexpected results will still be applicable across the claim scope (see MPEP 716.02).
It is further noted that the claims do not require that protection be demonstrated by an animal challenge study. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Additionally, Applicant has not provided any evidence that protection “must” be demonstrated via challenge. Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”) (MPEP 2145).
Lastly, Applicant’s reliance on HIV vaccine failures does not establish unpredictability for all vaccines. HIV presents unique challenges (e.g. viral replication, mutation, immune escape, latency) that have not been shown to be analogous to a noninfectious fungal toxin such as fumonisin B1. In particular, one major obstacle in developing an HIV-1 vaccine is the extraordinary genetic diversity of HIV-1, with multiple subtypes and strains circulating globally This diversity arises from the virus’s rapid mutation rate (i.e. 3.4 × 10-5 mutations per base in one replication cycle), particularly in the Env protein, resulting in millions of Env variants in an infected individual within 24 h. These Env variants can exhibit significant molecular and structural alterations, allowing the virus to evade host-mounted antibodies, making it exceedingly difficult to create a vaccine that can provide broad protection across all variants (Boomgarden et al, see Section 3: Why Is It Difficult to Develop an HIV-1 Vaccine?). Thus, the Applicant’s general assertion that vaccine efficacy is unpredictable based on HIV vaccine failures thus does not establish that skilled artisans would have lacked a reasonable expectation of success of the claimed method, particularly where applicant has not explained why unpredictability associated with HIV vaccines applies to immunization against the claimed noninfectious fungal toxin.
Therefore, the 35 USC 103 rejection is maintained.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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