DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group C in the reply filed on Dec 24, 2025 is acknowledged. Claims 1-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Dec 24, 2025.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on May 24, 2024 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 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.
4. Claims 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lipps et al., (US Patent 5,576,297 published Nov. 1996) in view of Hoffman [Dr Andrew Hoffman. December 14, 2014. https://www.petplace.com/article/horses/general/toxic-plants/].
The claims are drawn to a method for treating laminitis in an ungulate in need thereof, the method comprising administering a therapeutically effective amount of at least one anti-hemorrhagic peptide to the ungulate, thereby treating the laminitis.
Lipps et al., teach natural and synthetic lethal toxin neutralizing factors and their utility as treatment. Lipps et al., teach a method for treating a victim of envenomation, said method comprising injecting intravenously a composition into said victim, wherein said composition contains a lethal toxin neutralizing factor obtained from the sera of an opossum, wherein the victim has been envenomed from venom of all major species such as snakes, scorpions, bees and toxins from plants and bacteria. Opossum whole serum exhibits a lifesaving property by neutralizing the lethality of venoms from all major families of poisonous snakes, and therefore an injection of Opossum serum can used as a novel treatment for many types of envenomation. Preferably, the injectable treatment for envenomation should be a composition obtained from the fraction of Opossum whole serum which contains the lethal toxin neutralizing factor, i.e. the so called "natural LTNF", in purity [abstract]. Thus teaching claim 18. An antihemorrhagic factor in serum has been isolated and characterized (4). This antihemorrhagic factor has physical properties different from the immunoglobulins of serum [background]. Lipps teach (1) the lethal toxin neutralizing effect of opossum serum; (2) a purified component from opossum serum having lethal toxin neutralizing activity; and (3) a synthetic peptide having similar lethal toxin neutralizing activity for crude venoms of various species of snakes containing diverse deadly toxins acting in different physiological ways [background]. Lipps et al., teach a method of treating a victim of a bacterial toxin, plant toxin, and/or bee sting [claims 3, 5, and 9-11].
The use of both natural and synthetic LTNF can be extended to treat sepsis, allergy etc. and other nonspecific disorders [Object of the Invention]. The synthetic factor requires: (1) Amino acid sequencing of the purified LTNF from opossum serum; and (2) synthesizing a short peptide of fifteen amino acids, which is identical to the first 15 N terminal amino acids of the naturally occurring factor from opossum serum. The synthetic lethal toxin neutralizing factor and the first 15 N-terminal amino acids of the naturally occurring factor have the sequence [Summary of Invention]. Thus teaching claim 17. The lethal toxin neutralizing factor exhibits the ability to neutralize all effects associated with the lethality of snake venom toxins in mice [Summary of Invention].
The natural and synthetic LTNF, can be extended to treat scorpion and bee stings, and also toxins from plants, bacteria, etc. It is further believed that this invention has military applications due to the variety of unknown exposures that can occur under military conditions [Objects of the Invention]. The use of both natural and synthetic LTNF can treat sepsis, allergy etc. and other nonspecific disorders caused by environment [Objects of the Invention]. The activity of synthetic LTNF, which is similar to the natural LTNF, may extend to other toxins, viruses, allergens, etc. The synthetic LTNF is immunogenic, since mice immunized with it were able to produce specific antibodies, which reacted with both natural and synthetic LTNF, thus proving its biological potency. The use of natural and synthetic LTNF can treat sepsis, allergies and other nonspecific disorders caused by the environment and as a preventive measure before possible exposure to various toxins [Detailed Description of the Invention].
Therefore Lipps et al., teach administering a therapeutically effective amount of LTNF. The use of LTNF-n and LTNF-s is useful as treatment for sepsis, allergies and other nonspecific disorders caused by the environment and as a preventive measure before possible exposure to various toxins. The application of LTNF-n or LTNF-s, as treatment for snakebite, overcomes the problem of hypersensitivity occurring from the horse-derived antivenom [Detailed Description]. Lipps et al., teach SEQ ID NO:1
AAW11575
ID AAW11575 standard; peptide; 15 AA.
XX
AC AAW11575;
XX
DT 25-MAR-2003 (revised)
DT 20-MAR-1997 (first entry)
XX
DE N-terminal peptide from lethal toxin neutralising factor.
XX
KW Lethal toxin neutralising factor; LTNF; opossum; bee toxin;
KW scorpion toxin; plant toxin; bacterial toxin; venom; sting; snake bite.
XX
OS Didelphis virginiana.
XX
CC PN US5576297-A.
XX
CC PD 19-NOV-1996.
XX
CC PF 22-SEP-1994; 94US-00310340.
XX
PR 10-MAY-1993; 93US-00058387.
XX
CC PA (LIPP/) LIPPS B V.
CC PA (LIPP/) LIPPS F W.
XX
CC PI Lipps FW, Lipps BV;
XX
DR WPI; 1997-011287/01.
XX
CC PT Treatment of victims of bee or scorpion stings or plant or bacterial
CC PT toxins - by admin. of lethal toxin-neutralising factor or its N-terminal
CC PT peptide.
XX
CC PS Claim 7; Col 9; 9pp; English.
XX
CC The present sequence is from the N-terminus of a 68 kD protein purified
CC from the serum of the opossum Didelphis virginiana. The full-length
CC protein is a lethal toxin neutralising factor (LTNF). The use of purified
CC LTNF or of the chemically synthesised 15mer N-terminal peptide for
CC treating victims of bee stings, scorpion stings and bacterial or plant
CC toxins is claimed. The patent disclosure does not provide any evidence
CC for neutralising activity against these various toxins. There is evidence
CC of significant neutralising activity of the opossum LTNF and the 15mer
CC peptide against venom from snakes of the families Crotalidae, Elaphidae,
CC Hydrolidae and Viperidae. (Updated on 25-MAR-2003 to correct PF field.)
XX
SQ Sequence 15 AA;
Query Match 100.0%; Score 84; DB 1; Length 15;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LKAMDPTPPLWIKTE 15
|||||||||||||||
Db 1 LKAMDPTPPLWIKTE 15
Lipps et al., teach SEQ ID NO: 2
AAW11575
ID AAW11575 standard; peptide; 15 AA.
XX
AC AAW11575;
XX
DT 25-MAR-2003 (revised)
DT 20-MAR-1997 (first entry)
XX
DE N-terminal peptide from lethal toxin neutralising factor.
XX
KW Lethal toxin neutralising factor; LTNF; opossum; bee toxin;
KW scorpion toxin; plant toxin; bacterial toxin; venom; sting; snake bite.
XX
OS Didelphis virginiana.
XX
CC PN US5576297-A.
XX
CC PD 19-NOV-1996.
XX
CC PF 22-SEP-1994; 94US-00310340.
XX
PR 10-MAY-1993; 93US-00058387.
XX
CC PA (LIPP/) LIPPS B V.
CC PA (LIPP/) LIPPS F W.
XX
CC PI Lipps FW, Lipps BV;
XX
DR WPI; 1997-011287/01.
XX
CC PT Treatment of victims of bee or scorpion stings or plant or bacterial
CC PT toxins - by admin. of lethal toxin-neutralising factor or its N-terminal
CC PT peptide.
XX
CC PS Claim 7; Col 9; 9pp; English.
XX
CC The present sequence is from the N-terminus of a 68 kD protein purified
CC from the serum of the opossum Didelphis virginiana. The full-length
CC protein is a lethal toxin neutralising factor (LTNF). The use of purified
CC LTNF or of the chemically synthesised 15mer N-terminal peptide for
CC treating victims of bee stings, scorpion stings and bacterial or plant
CC toxins is claimed. The patent disclosure does not provide any evidence
CC for neutralising activity against these various toxins. There is evidence
CC of significant neutralising activity of the opossum LTNF and the 15mer
CC peptide against venom from snakes of the families Crotalidae, Elaphidae,
CC Hydrolidae and Viperidae. (Updated on 25-MAR-2003 to correct PF field.)
XX
SQ Sequence 15 AA;
Query Match 100.0%; Score 54; DB 1; Length 15;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LKAMDPTPPL 10
||||||||||
Db 1 LKAMDPTPPL 10
Therefore, Lipps et al., teach a method for treatment with LTNF; the method comprising administering a therapeutically effective amount of at least one anti-hemorrhagic peptide to the victim, thereby treating the laminitis. However Lipps et al., do not teach the victim is an ungulate and does not correlate plant toxins and laminitis.
Hoffman teach foreign plants can colonize a pasture from remote sources of seed, sometimes conquering large flats in a single year. Fields that are poorly managed, previously flooded, overgrazed, or surrounded by overgrown fields may be prone to weed infestation. Horses that are grazed next to woodlands, roads, ornamental gardens, lawns, or orchards are particularly prone towards toxicity. Take a walk around your pasture and get a sense of what's new? Pasture is the main source of toxic plants, but hay can be another. Hay is viewed as suspect in cases where there is no pasture. Exceptions include Yew (Taxus) or Water Hemlock (Cicuta douglasii) which are quite deadly – fortunately, horses rarely have access to these plants. Goats, on the other hand, seem to get into trouble with them, while satisfying their curious appetites.
Horses often resort to eating toxic plants in times of drought, when pastures are sparse, grazing on recaptured land, with access to woodlands, and in malnourished states, horses. Horses denied forage, roughage, salt, minerals, horses that are fed 'complete feed' pellets instead of hay (old horses with bad teeth), and horses that are bored may start nibbling on toxic plants.
Plant toxicosis should be considered in any horse with unexplained signs of slobbering, laminitis, sudden onset of tremors or weakness, behavioral changes, bloody diarrhea, red urine, cardiac arrhythmias, jaundice or other signs of liver disease, severe anemia, and in cases of sudden death, plant toxicity. Hoffman reviews plant toxicities by the symptoms they produce.
The most serious lameness is caused by Black walnut (Juglans nigra), which induces serious laminitis. Hence, it is imperative that a horse is not bedded on shavings made from these walnuts. Another plant, Hoary alyssum (Berteroa incana) causes limb edema, fever, and laminitis, confusing the diagnosis of Ehrlichia equi and purpura hemorrhagica (secondary to strangles) in some horses. Hoary alyssum toxicity has been reported from consumption of contaminated hay.
The principal systemic symptom consists in the alteration of blood clotting, due to fibrinogen consumption and platelet abnormalities. The horses involved in this study had this symptomatology and one of them exhibited symptoms consistent with laminitis in the bitten and in the contralateral limbs. Laminitis lesions were characterized by separation of the hoof lamellar basement membrane (BM) from basal cells of the epidermis. [abstract].
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Lipps et al’s LTNF within a method of treating laminitis as a result of allergy or consumption of a poisonous plant and its toxins, when Hoffman teach laminitis results from ingesting poisonous plant toxins while the LTNF is known to be used to treat plant allergies and toxins from plants. One of ordinary skill in the art would have a reasonable expectation of success in treating laminitis resulting from plant toxins when Lipps et al., specifically teach LNTF displays can treat reactions to plant toxins, allergy other nonspecific disorders caused by environment.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of treating laminitis in an ungulate, where there is no change in the respective function of the LNTF or plant toxicosis, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claim Rejections - 35 USC § 103
5. Claims 16-20, are rejected under 35 U.S.C. 103 as being unpatentable over Lipps et al., (US Patent 5,576,297 published Nov. 1996) in view of
Kentucky Equine Research Staff (December 1, 2004. https://ker.com/equinews/laminitis-triggering-allergens/)
Lipps et al., has been discussed above for teaching a method for treating laminitis in an ungulate in need thereof, the method comprising administering a therapeutically effective amount of at least one anti-hemorrhagic peptide to the ungulate, thereby treating the allergy plant poisoning with can cause laminitis. However Lipps et al., do not teach the victim is an ungulate and does not correlate allergy and plant toxins to laminitis.
The Kentucky Equine Research Staff teach laminitis triggering allergens. Kentucky Equine Research Staff review a study at Texas A&M University has discovered a link between hypersensitivity and laminitis. Foundered horses that were skin-tested for common allergens showed significantly larger and longer-lasting reactions than healthy horses. This result indicates that laminitis flare-ups may be triggered by allergens and also by reactions to ingredients in common vaccines. Researchers say that it may be safer to spread out vaccinations for horses with chronic laminitis, rather than administering several vaccinations on the same day.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Lipps et al’s LTNF within a method of treating allergies and allergens which Kentucky Equine Research Staff teach laminitis triggering allergens, in order to treat the effects of laminitis in ungulates. Kentucky Equine Research Staff teach allergen triggered laminitis while the LTNF is known to be used to treat allergies, and allergens. One of ordinary skill in the art would have a reasonable expectation of success in treating laminitis resulting from allergens when Lipps et al., specifically teach LNTF can treat allergic reactions and other nonspecific disorders caused by environment.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of treating laminitis in an ungulate, where there is no change in the respective function of the LNTF or allergens, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Pertinent Art
6. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Acosta de Perez et al., (Toxicon, Volume 48, Issue 3, 1 September 2006, Pages 307-312). Acosta de Perez et al., teach envenoming caused by Bothrops snakebite
includes local symptoms, such as pronounced edema, hemorrhage, intense pain,
vesicles, blisters and myonecrosis [Abstract]. Lameness (claudication) and dysfunction
of the bitten limb has been observed in horses after natural snakebite presumably
because of the rapid effect of the venom in the bitten area. Chronic laminitis has been
listed as a sequelae to snakebite in horses [Introduction]. The principal systemic symptom consists in the alteration of blood clotting, due to fibrinogen consumption and platelet abnormalities. The horses involved in this study had this symptomatology and one of them exhibited symptoms consistent with laminitis in the bitten and in the contralateral limbs. Laminitis lesions were characterized by separation of the hoof lamellar basement membrane (BM) from basal cells of the epidermis. These results demonstrated that Bothrops snake venom induces acute laminitis. We conclude that components of the venom, probably metalloproteinases, cause severe lesions in the hoof early in the envenoming process. Antivenom therapy must be initiated as soon as possible in order to prevent complications, not only to save the life of an envenomed horse, but also to avoid the dysfunctional sequels of laminitis [abstract].
Boucher (US Patent Pub 20110189166 published Aug 2011; priority to Jan 2010) teach methods of treating hemorrhagic abnormalities in horses are provided,
Boosman et al., The Role of endotoxins in the pathogenesis of acute bovine laminitis (The Vet Quarterly, Vol. 13, No 3, July 1991).
Galey et al., Black walnut (Juglans nigra) toxicosis: a model for equine laminitis (J Comp Pathol. 1991 Apr:104(3):313-26).
Endotoxins: Substantial Tigger Factor for Laminitis. [21 March 2013. https://www.thedairysite.com/articles/3515/endotoxins-substantial-trigger-factor-for-laminitis/]
Endotoxins are substantial triggers factors for laminitis. Laminitis is considered to be the third biggest health issue in the industry, and has been linked the condition to carbohydrate overload culminating in a release of endotoxins into the bloodstream. Laminitis is a disease in ungulates that is most commonly found in horses and cows. Laminitis is an inflammation of the lamella tissue of the hoof/claw. It is a painful disease for animals and leads to huge financial losses in the horse and dairy industry [Laminitis]. A lot of factors can influence the prevalence and severity of laminitis. Most of them can be avoided by appropriate feed and health management strategies. The following are some of the most common factors influencing laminitis in horses and cows:
Predisposing diseases in horses include colic, endotoxemia and/or septicemia, equine metabolic disease, Cushing's syndrome
Predisposing diseases in cows include acidosis, mastitis, metabolic disease
Extensive amounts of high energy feed (especially in high performance cows.)
Grain-based or pasture-induced carbohydrate overload
Obesity (especially in ponies)
Hoof/claw care
Stable management (design, bedding material)
Extensive exercise for horses (especially on hard surfaces)
Presence of environmental toxins (endotoxins. mycotoxins, exotoxins)
Conclusion
7. No claims allowed.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Gary Nickol, can be reached on 571-272-0835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645