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 .
Priority
The instant application, filed on 07, December 2023, claims domestic benefit to US provisional application no. 63/431,147 filed on 08, December 2022.
Status of Application, Amendments, and/or Claims
The response filed on 07 December, 2023 has been entered in full. No amendments or withdrawals have been made. Therefore, claims 1-13 are pending and are the subject of this Office Action.
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.
Claim 9 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 9 recites “wherein the at least one additional agent comprises polyclonal antibodies or antigen binding fragments thereof.” Claim 9 depends on claim 8 which recites “wherein the at least one additional agent is a monoclonal antibody or antigen binding thereof.” It is unclear if the polyclonal and monoclonal antibodies should be together or are alternative options. For the purpose of further examination and in light of the specification which recites “in some examples on or more monoclonal antibodies or antigen binding fragments thereof that bind to a snake antigen can be combined with the described FETUA-3 protein” (pg.10, lines 25-27-) and “In some examples an additional agent comprises a polyclonal antibody preparation” (pg.10, lines 28-31), and further does not describe an example where they are used in combination, the claim will be interpreted to be an alternative option to a monoclonal antibody.
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.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Albulescu et al. (2020) Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite Sci. Transl. Med. 12, eaay8314 (hereafter Albulescu) in view of NCBI Reference Sequence XP_039207923 (02/05/2021), Lewin (US2021/0260029, Pub 08/26/2021), Seneci et al. (2021) A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms Front. Immunol. 12:612846 (hereafter Seneci), Gutierrez et al. (2021) The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming Toxins 13, 451 (hereafter Gutierrez) and Raweerith and Ratanabanangkoon (2005) Immunochemical and biochemical comparisons of equine monovalent and polyvalent snake antivenoms Toxicon 45 369-375.
Albulescu in regards to claims 1 and 7 teaches treating injury from envenomation by a snake in the Echis genus using a composition comprising 2,3-dimercapto-1-propanesulfonic acid (DMPS). DMPS is a snake venom metalloproteinase (SVMP) inhibitor like SEQ ID NO: 1 (pg.3, col 1, lines 10-14).
In regards to claims 4, 5, and 8 Albulescu teaches following DMPS administration with EchiTAbG antivenom (a monospecific antibody) (pg.6, col 2, lines 31-33/ Figure 7).
In regards to claim 10 Albulescu teaches the antivenom treatment in combination with the SVMP inhibitor improved long term survival of a murine model, as compared to the antivenom alone (Figure 7).
Albulescu fails to teach SEQ ID NO: 1 of claims 1, 7, and 10, the snake species of claim 2, the inhibition of injury comprising reduced proteolysis of collagen, fibrinogen, or a combination thereof of claim 3, the individual being a human, canine, feline, equine, porcine or bovine of claim 6, and the additional agent comprising polyclonal antibodies or antigen binding fragments of claims 9 and 10.
NCBI Reference Sequence XP_039207923, however, in regards to claims 1 and 7 teaches an antihemorrhagic factor cHLP-A protein with a 95.7% match to SEQ ID NO: 1 (see Examiner Figure 1).
PNG
media_image1.png
677
852
media_image1.png
Greyscale
Examiner Figure 1: SEQ ID NO:1 alignment to Sequence XP_039207923
NCBI Reference Sequence XP_039207923 fails to teach the snake species of claim 2, the inhibition of injury comprising reduced proteolysis of collagen, fibrinogen, or a combination thereof of claim 3, the individual being a human, canine, feline, equine, porcine or bovine of claim 6, and the additional agent comprising polyclonal antibodies or antigen binding fragments of claims 9 and 10.
Seneci , however, in regards to claim 2 teaches that metalloproteinase inhibitor Prinomastat was effective in neutralizing the procoagulant venom activity in Crotalus culminatus snakes (Figure 3/ pg.6, col 2, line 52- pg.7, col 1, line 2), and highlights using it as an adjunct treatment (pg.19, col 1, lines 32-35), and further highlighting the metalloproteinase inhibition is effective in a snake of the genus Crotalus, which are responsible for most snakebite envenoming in the United States and significant portions of Latin America (pg.1, col 1, lines 21-26).
In regards to claim 3 Seneci teaches that fibrinogen depletion can occur in two ways, one of which is via direct degradation by kallikrein-type serine proteases or metalloproteases (pg.1, col 2, lines 34-39), and further teaches that the use of a metalloprotease inhibitor can increase the clotting time of plasma in the presence of a venom (Figure 3).
Seneci fails to teach the individual being a human, canine, feline, equine, porcine or bovine of claim 6, and the additional agent comprising polyclonal antibodies or antigen binding fragments of claims 9 and 10.
Gutierrez, however, in regards to claim 6 teaches that snakebite envenoming is an impactful global health problem resulting in 81,000 to 138,00 fatalities and more than 400,000 people (humans) left with permanent sequelae (pg.1 , lines 1-5). Gutierrez also teaches that improvements to antivenoms are necessary to help with this problem, and a way to approach this is by introducing inhibitors to complement antivenoms (pg.2, lines 15-17/ pg.3 lines 17-19). Further, Gutierrez specifically discusses repurposing SVMP inhibitors which have already shown clinical success in other diseases (pg.3, lines 19-22).
Gutierrez fails to teach the additional agent comprising polyclonal antibodies or antigen binding fragments of claims 9 and 10.
Raweerith and Ratanabanangkoon, however, in regards to claims 9 and 10 teach monovalent (monoclonal) antivenoms have specific antibody against a particular venom (pg.370, col 1, lines 4--6) while polyvalent (polyclonal) antivenoms contain specific antibodies capable of neutralizing a number of venoms (pg.370, col 1, lines 18-20). Further Raweerith and Ratanabanangkoon teaches that polyvalent antivenoms can be prepared against all relevant snakes in a particular area and be administered immediately to severely envenomed victims without need to identify the snake contributing to the remarkable decrease in mortality rates (pg.370, col 1, lines 20-27).
Claims 11-13 refer to a kit comprising the components claimed in claims 1-10 without adding further limitation and thus the kit does not preclude the method or the composition.
Thus, Albulescu discloses a method and composition for treating snake envenomation comprising administering a monospecific antivenom in conjunction with a SVMP inhibitor to improve long term survival, NCBI Reference Sequence XP_039207923 teaches a sequence with 95.7% sequence similarity to SEQ ID NO:1 and teaches it is a antihemorrhagic factor from a Crotalus tigris snake, Seneci teaches that SVMP inhibitors also work in Crotalus genus snakes as an adjunct treatment and further that it works by inhibiting the degradation of fibrinogen, Gutierrez teaches that snake envenomation is a public health problem for humans and further teaches improvement to antivenom is needed and a method to do this is by introducing complementary inhibitors such as an SVMP inhibitor, and Raweerith and Ratanabanangkoon teach monovalent and polyvalent antivenoms bind to one or more venom components respectively and highlights the benefits or choosing a polyvalent antivenom over a monovalent antivenom. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Albulescu, sequence XP_039207923, Seneci, Gutierrez, and Raweerith and Ratanabanangkoon with a reasonable expectation of success to develop a method or composition for treat human snake envenomation comprising a SVMP inhibitor with 95% sequence identity to SEQ ID NO:1 and specific to Crotalus snakes due to their prevalence in snakebite injuries in the US and areas of Latin America, and a monospecific or polyspecific antivenom for a more targeted or a more universal treatment respectively, to address a public health issue and to improve upon current treatments.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday- Thursday from 8am to 6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. 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 Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center to authorized users only. Should you have questions about access to the USPTO patent electronic filing system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via a variety of formats. See MPEP § 713.01. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/InterviewPractice.
/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights