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 .
Status of Claims
Claims 1, 24, 28, and 34 are amended. Claims 54-58 are added. Claims 1, 17, 24, 26, 28-29, 32-38, 40-41, 48, 50-51 and 53-58 are currently pending and under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 17, 24, 26, 28-29, 32-38, 40-41, 48, 50-51 and 53-58 have an earliest effective filing date of 04/20/2020, corresponding to provisional applications 63/012,786 and 63/012,783.
Information Disclosure Statement
The Information Disclosure Statement filed on 10/16/2025 has been considered.
Response to Remarks filed 10-16-2025
Applicant’s arguments and amendments regarding the 35 USC 112a rejection have been fully considered and are persuasive. Specifically removal of the preventing language remedies the rejection. Therefore, the 35 USC 112a rejection is withdrawn.
Applicant’s arguments and amendments regarding the 35 USC 102 rejection have been fully considered and persuasive. Therefore, the 35 USC 102 rejection is withdrawn.
Applicant’s arguments and amendments regarding the 35 USC 103 rejection have been considered and are not persuasive. Although addition of the 15mg/kg overcomes the 102 rejection of claim 1, it is prima facie obvious as detailed below. Therefore the 35 USC 103 rejection is maintained.
New Rejections Necessitated by Amendments
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 1, 17, 24, 26, 28, 29, 32, 34-38, 40, 41, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Rousseau et al (US20130315914 published 11/28/2013) as evidenced by Peiris et al (The Lancet, 361;1319-1325, 2003) and Wilder-Smith et al (Emerging Infectious Diseases, 11;7, 1142-1145, 2005).
Rousseau et al teach the use of the humanized antibody 15C1 in treating symptoms induced by an LPS model of ARDS (Rousseau et al, pg. 31, paragraph 0211). Antibody 15C1 of the referenced application comprises VH of reference SEQ ID NO: 43 (comprising 100% of instant SEQ ID NOs: 1-3, and 36) and VL of reference SEQ ID NO: 4 (comprising 100% of instant SEQ ID NOs: 4-6, and 42) (Rousseau et al, pg. 31, paragraph 0211-0212). Therefore, Rousseau et al meet all the limitations of claims 1, 17, and 24.
Therefore Rousseau et al teach the use of a TLR4 antibody in the treatment of symptoms of ARDS. However, Rousseau et al do not teach the use of a TLR4 antibody in the treatment of symptoms of ARDS wherein the antibody is administered at 15 mg/kg.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to modify the teachings of Rousseau et al to arrive at a method of using of a TLR4 antibody in the treatment of symptoms of ARDS induced by LPS wherein the antibody is administered at 15 mg/kg. One of ordinary skill in the art would have been motivated to do so, because Rousseau et al teach the use of a TLR4 antibody in the treatment of symptoms of ARDS. Furthermore, It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
As such one of ordinary skill in the art would have been motivated to modify the teachings of Rousseau et al to further include a dose of 15mg/kg, because there would have been a reasonable expectation that the resultant invention, which comprises treating symptoms of ARDS with a TLR4 antibody at 15mg/kg, was effective at treating symptoms of ARDS.
Regarding claim 24, the method of claim 1 is discussed above. Rousseau et al teach that the antibody is humanized (Rousseau et al, pg. 7, paragraph 0042).
Regarding claim 26, the method of claim 1 is discussed above. Rousseau et al teach that the antibody can be IgG1 (Rousseau et al, pg. 4-5, paragraph 0022).
Regarding claim 28, the method of claim 26 is discussed above. Rousseau et al teach that the antibody comprises the amino acid sequence SKAF comprising reference SEQ ID NO: 42 at EU positions 325-328 (Rousseau et al, pg. 5, paragraph 0023, instant SEQ ID NO: 193).
Regarding claim 29, the method of claim 1 is discussed above. Rousseau et al further teach the antibody can be administered by inhalation, intravenously, or subcutaneously (Rousseau et al, pg. 29, paragraph 0197).
Regarding claim 32, the method of claim 1 is discussed above. Rousseau et al further teach the common dosing frequencies from twice daily to once a week (Rousseau et al, pg. 28, paragraph 0188). It is noted that twice daily meets the limitation of at least 2 times and once a week meets the limitation of at least one time.
Regarding claims 34, 36-38, and 40, the method of claim 1 is discussed above. Rousseau et al further disclose the use of the antibody for treating the symptoms of fever and confusion (Rousseau et al, pg. 28, paragraph 0182). Regarding claims, 36-38 and 40, it is noted that fever is a common symptom of people with coronavirus induced ARDS (Peiris et al, pg. 1320, Table 1). Regarding claim 38, It is further noted that it is an inherent feature of coronavirus to be asymptomatic in some patients (Wilder-Smith et al, pg. 1142, Abstract).
Regarding claim 35, the method of claim 1 is discussed above. Rousseau et al further teach the antibody for use in treating a patient with sepsis (Rousseau et al, pg. 27, paragraph 0178).
Regarding claim 41, the method of claim 1 is discussed above. Rousseau et al further teach the antibody can be used in combination with cytokines, an immune booster drug (Rousseau et al, pg. 29, paragraph 0190).
Regarding claim 54, at [0008] and [0009], Rousseau et al. teach monoclonal antibodies.
Claim(s) 48, 50, 55, and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Rousseau et al (US20130315914 published 11/28/2013) in view of Monnet et al (Clinical Pharmacology and Therapeutics 101;2, 2017, published 02/02/2017) as evidenced by Peiris et al (The Lancet, 361;1319-1325, 2003) and Wilder-Smith et al (Emerging Infectious Diseases, 11;7, 1142-1145, 2005).
Regarding claim 48, Rousseau et al teach the use of the humanized antibody 15C1 in an LPS model used to induce symptoms of ARDS (Rousseau et al, pg. 31, paragraph 0211). Antibody 15C1 of the referenced application comprises VH of reference SEQ ID NO: 43 (comprising 100% of instant SEQ ID NOs: 1-3, and 36) and VL of reference SEQ ID NO: 4 (comprising 100% of instant SEQ ID NOs: 4-6, and 42) (Rousseau et al, pg. 31, paragraph 0211-0212).
Monnet et al teach a composition comprising an antibody that binds specifically to TLR4, NI-0101, which comprises instant SEQ ID NOs: 1-6, L-histidine (1.88 mg/mL), L-histidine monohydrochloride monohydrate (2.70 mg/mL), sucrose (68.46 mg/mL), and polysorbate 80 (0.05 mg/mL) (Monnet et al, pg. 206, column 2, paragraph 4).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Rousseau et al and Monnet et al to arrive at a method of using of a TLR4 antibody in the treatment of symptoms of ARDS induced by LPS wherein the antibody is administered at 15 mg/kg. One of ordinary skill in the art would have been motivated to do so, because Rousseau et al teach the use of a TLR4 antibody in the treatment of symptoms of ARDS and Monnett et al teach the excipients and compositions that can be used to administer the antibody. Furthermore, It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Regarding claims 55 and 56, Monnet et al teach the antibody is a monoclonal, humanized antibody (Monnet et al, paragraph 1).
Claim(s) 51, 53, 57, and 58 is rejected under 35 U.S.C. 103 as being unpatentable over Rousseau et al (US20130315914 published 11/28/2013) in view of Monnet et al (Clinical Pharmacology and Therapeutics 101;2, 2017, published 02/02/2017) and Tantawy et al (PharmaNutrition, Vol 8, 1-5, 2019; published 04/25/2019).
Regarding claim 51, Rousseau et al teach the use of the humanized antibody 15C1 in treating symptoms of ARDS (Rousseau et al, pg. 31, paragraph 0211). Antibody 15C1 of the referenced application comprises VH of reference SEQ ID NO: 43 (comprising 100% of instant SEQ ID NOs: 1-3, and 36) and VL of reference SEQ ID NO: 4 (comprising 100% of instant SEQ ID NOs: 4-6, and 42) (Rousseau et al, pg. 31, paragraph 0211-0212). Monnet et al teach a composition comprising an antibody that binds specifically to TLR4, NI-0101, which comprises instant SEQ ID NOs: 1-6, L-histidine (1.88 mg/mL), L-histidine monohydrochloride monohydrate (2.70 mg/mL), sucrose (68.46 mg/mL), and polysorbate 80 (0.05 mg/mL) (Monnet et al, pg. 206, column 2, paragraph 4).
Monnet et al doesn’t teach a pharmaceutical composition comprising L-Arginine and L-Arginine monohydrochloride. This is remedied by Tantawy et al.
Tantawy et al teach that L-Arginine may be used in therapeutic compositions and is more available than L-Histidine (Tantawy et al, pg. 3, Section 4). It would be obvious to combine the teachings of Monnet et al and Tantawy et al to modify the invention of Monnet et al to replace L-histidine with L-Arginine and L-histidine monohydrochloride with L-arginine monohydrochloride because one of ordinary skill in the art at the effective filing date would have had a reasonable expectation of success of creating an effective antibody composition. One of ordinary skill in the art would have been motivated to do so because L-Arginine is more available than L-Histidine and can be used to increase production.
The exact doses of claim 51 are not disclosed. However, it is noted that one of ordinary skill in the art would be motivated to find the best concentrations for each ingredient by routine optimization making the doses obvious.
Therefore claim 51 was prima facie obvious at the time of effective filing.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
Regarding claims 57 and 58, Monnet et al teach the antibody is a monoclonal, humanized antibody (Monnet et al, paragraph 1).
Conclusion
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.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE K DARPOLOR whose telephone number is (571)272-0115. The examiner can normally be reached 7:30ET-4:30ET.
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, Samira Jean-Louis can be reached at (571)270-3503. 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.
/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642