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 .
DETAILED ACTION
Pursuant to the amendment dated 12/18/2025, claims 1, 10, and 11 are amended and claims 16 and 17 are newly added. Claims 1-17 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/EP2021/083899, filed on 12/02/2021 and claims foreign priority to EPO 20211553.1 filed on 12/03/2020.
Information Disclosure Statement
The information disclosure statement (IDS) dated 12/18/2025 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Withdrawn Rejections
Applicant’s amendment, filed on 12/18/2025, with respect to the rejection of claims 10 and 11 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, has been fully considered and is persuasive. Applicant has amended claims 10 and 11 to remove the “preferably” language. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 12/18/2025, with respect to the rejection of claims 1-15 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement, has been fully considered and is persuasive. Applicant has amended claim 1 to remove the phrase “preventing”. The rejection is hereby withdrawn.
Rejections Necessitated by Amendment
The following are maintained and new ground(s) necessitated by Applicants' amendment, filed on 12/18/2025, wherein instant independent claims 1 was amended to alter the breadth and scope of the claim, and wherein the remaining pending claims 2-17 depend from said independent claims.
New or Maintained Grounds of Rejection
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, 2 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Kleefield et al. (WO 2014/187957 Al, published 11/27/2014, see PTO-892).
Kleefield is drawn to tylosin derivatives of formula (I1a), a pharmaceutical or veterinary composition comprising the derivatives, and a method for treating bacterial infections in an animal (abstract). The composition may comprise therapeutically effective amount of the compound and one or more pharmaceutically acceptable excipients or carriers (page 35, lines 4-6). The carriers may be liquid, diluent, excipient, solvent or encapsulating material (page 36, lines 12-13). The bacterial infections and disorders related to such infections may be treated in animals include cow foot rot related to infection by Fusobacterium spp. (page 34, line 1). The compound may be administered to the subject either prior to or after the onset of a bacterial infection and can be a bolus injection (page 35, lines 19-21). Formula I1a can be tildipirosin when R11 and R12 are taken with the nitrogen atom to which they are connected to form a 6 membered ring (page 6, lines 20-21) and R5 is N-Y2 when the two Y are taken with the nitrogen atom to which they are connected to form a 6 membered ring (page 7, lines 8-10),
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Kleefield Formula I1a.
Kleefield does not exemplify a pharmaceutical composition comprising tildipirosin for the treatment of foot rot.
It would have been prima facie obvious before the effective filing date of the claimed invention to use a pharmaceutical composition comprising tildipirosin in injection form to treat foot rot in cattle as taught by Kleefield to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to use the pharmaceutical composition comprising tildipirosin in injection form to treat foot rot in cattle because Kleefield teaches that tylosin derivatives, of which tildipirosin is one, may be used in pharmaceutical compositions as a bolus injection and may be used to treat foot rot in cattle. One of ordinary skill in the art would have a reasonable expectation of success because Kleefield teaches a pharmaceutical composition comprising tildipirosin in injection form to treat foot rot in cattle.
Claims 3, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Kleefield et al. (WO 2014/187957 Al, published 11/27/2014, see PTO-892) as applied to claim 1 above, and further in view of Huang et al. (CN 106943349 A, published 07/14/2017, accessed 09/20/2025, see PTO-892).
Claim 1 is rejected as discussed above.
The teachings of Kleefield are discussed above.
Kleefield further teaches that the pharmaceutically acceptable salt of the compound may be employed (page 6 line 3, and page 38 line 6).
Kleefield does not teach the injectable pharmaceutical composition is a suspension.
Huang discloses a tildipirosin suspension injection wherein the suspension injection of the invention has a slow-release effect and can maintain the effective blood concentration of the target animal for a longer time which can improve the curative effect of the medicine (abstract).
It would have been prima facie obvious to combine the teachings of Kleefield and Huang before the effective filing date by modifying the injectable pharmaceutical composition comprising tildipirosin for treatment of foot rot in cattle as taught by Kleefield to be in a suspension as taught by Huang to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the composition to be in a suspension because Huang teaches that the suspension has a slow-release effect and can maintain the effective blood concentration of the target animal for a longer time which can improve the curative effect of the medicine. One of ordinary skill in the art would have a reasonable expectation of success because Huang teaches an injectable tildipirosin suspension composition and Kleefield teaches that a pharmaceutical composition comprising tildipirosin may be used to for treatment of foot rot in cattle.
Regarding claim 14, it would have been prima facie obvious to combine the teachings of Kleefield and Huang before the effective filing date by selecting a salt of tildipirosin for the pharmaceutical composition as taught by Kleefield for the injectable pharmaceutical composition suspension as taught by the combined teachings of Kleefield and Huang to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select the salt of tildipirosin because Kleefield teaches that the compound for use in a pharmaceutical composition may be a salt of tildipirosin. One of ordinary skill in the art would have a reasonable expectation of success because Kleefield teaches that the compound for use in a pharmaceutical composition may be a salt of tildipirosin
Claims 3-6, 8, 9, 11, 12 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Kleefield et al. (WO 2014/187957 Al, published 11/27/2014, see PTO-892) as applied to claim 1 above, and further in view of He et al. (CN 105919933 A, published 09/07/2016, accessed 09/20/2025, see PTO-892).
Claim 1 is rejected as discussed above.
The teachings of Kleefield are discussed above.
Kleefield also teaches that the compounds, which may include tildipirosin, may be used in the treatment of bovine respiratory disease related to infection by P. haemolytica, P. multocida, Mycoplasma bovis, or Bordetella spp (page 33, lines 22-23).
Kleefield does not teach the addition of propylene glycol, water, or citric acid.
He is drawn to tildipirosin injection formulations wherein the injection comprises the following mass percentage of each component: tildipirosin 4 to 20 %, a pH regulator 1 to 9 %, an organic solvent 30 to 50 %, and water is added to 100 % (abstract). He teaches that for the tildipirosin injection solution preferably the organic solvent is propylene glycol and the pH regulator is citric acid (page 2). He further teaches that tildipirosin is a broad-spectrum antibacterial medicine that has antibacterial activity for some Gram-positive and Gram-negative bacteria and is especially sensitive to pathogenic bacteria causing pig, cattle and sheep respiratory system disease, such as actinobacillus pleuropneumoniae, pasteurellamultocida, bronchisepticale, Haemophilus parasuis and hemolysis Manhaim bacteria, sleep tissue bacteria and so on (page 2). He also teaches that the tildipirosin has a wide application prospect (page 3).
It would have been prima facie obvious to combine the teachings of Kleefield and He before the effective filing date of the claimed invention by optimizing the amounts of tildipirosin, propylene glycol, and citric acid as disclosed by He for the composition taught by Kleefield for the treatment of foot rot in cattle to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to optimize the concentration within the range disclosed because He teaches a tildipirosin composition comprising 4 to 20% mass percentage tildipirosin, 1 to 9% by mass citric acid, and 30 to 50% propylene glycol and water added to 100%. One of ordinary skill in the art would have a reasonable expectation of success because He teaches that tildipirosin is a broad-spectrum antibacterial medicine especially to pathogenic bacteria causing cattle respiratory system disease and Kleefield teaches that tildipirosin may be used against both bacteria for bovine respiratory system disease and cattle foot rot In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. 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). (MPEP § 2144.05(I)) Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Claims 7, 10, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Kleefield et al. (WO 2014/187957 Al, published 11/27/2014, see PTO-892) as applied to claim 1 above, and further in view of FDA et al. (FDA Freedom of Information Summary, published 05/14/2012, see IDS dated 08/22/2023).
Claim 1 is rejected as discussed above.
The teachings of Kleefield are discussed above.
Kleefield does not teach wherein the tildipirosin is the form of the free base or the tildipirosin dosage per body weight of the animal.
FDA discloses an 18% injectable solution of tildipirosin for beef cattle (title). The injectable solution is for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in beef and non-lactating dairy cattle (abstract). FDA teaches that tildipirosin inhibits essential bacterial protein biosynthesis with selective binding to ribosomal subunits in a bacteriostatic and time-dependent manner. FDA exemplified a single subcutaneous injection of tildipirosin at 180 mg/mL at 2, 4, and 6 mg/kg body weight of calve (page 2). FDA teaches the use of tildipirosin in the form of the free base in a toxicity experiment (page 25).
It would have been prima facie obvious to combine the teachings of Kleefield and FDA before the effective filing date of the claimed invention by selecting the free base form of tildipirosin for the pharmaceutical composition comprising tildipirosin for the treatment of foot rot in cattle as taught by Kleefield to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select the free base form of tildipirosin because FDA exemplified the use of the free base form of tildipirosin in a pharmaceutical composition. One of ordinary skill in the art would have a reasonable expectation of success because He shows that free base form of tildipirosin may be used in a pharmaceutical composition.
Regarding claim 10, it would have been prima facie obvious to combine the teachings of Kleefield and FDA before the effective filing date of the claimed invention by optimizing the dosage by body weight of the animal of tildipirosin as disclosed by FDA for the composition taught by Kleefield for the treatment of foot rot in cattle to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to optimize the dosage by body weight of the animal of tildipirosin because FDA teaches a single subcutaneous injection of tildipirosin at 180 mg/mL at 2, 4, and 6 mg/kg body weight of calve. One of ordinary skill in the art would have a reasonable expectation of success because FDA teaches that the tildipirosin injection may be used against Mannheimia haemolytica and Pasteurella multocida bacteria causing cattle respiratory system disease and Kleefield teaches that tildipirosin may be used against both bacteria for respiratory system disease and cattle foot rot. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. 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). (MPEP § 2144.05(I)) Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Response to Arguments
Applicant's arguments filed 12/18/2025 have been fully considered but they are not persuasive.
Applicant argues that Kleefield does not exemplify a pharmaceutical composition comprising tildipirosin for the treatment of foot rot and that the effectiveness of an antibiotic compound against any specific bacterium is highly unpredictable. Therefore, knowledge that other tylosin derivatives are active against other species of bacteria would not provide one skilled in the art with an expectation of success that tildipirosin would be an effective treatment of a foot rot infection caused by Fusobacterium spp. Applicant argues that disclosure of tildipirosin's activity against Fusobacterium spp and/or its use as a treatment of foot is absent from the cited references. The argument is not persuasive. Kleefield is drawn to tyolsin derivatives with a specific structure (Formula IIa) that encompasses tildipirosin. "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton."KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle."Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ."Id. at 418, 82 USPQ2d at 1396 (see MPEP2141). One of ordinary skill in the art would have a reasonable expectation of success because Kleefield teaches the compounds of Formula IIa, which encompasses tildipirosin, and teaches that the compounds of Formula IIa can be used to treat cow footrot related to infection by Fusobacterium spp.. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693