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 .
Formal Matters
Applicant’s claim amendments and arguments in the reply filed on 10 November 2025 are acknowledged and have been fully considered. Claims 1-12 are pending. Claims 1-10 are under consideration in the instant office action. Claims 11-12 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 2-10 are amended. Applicant’s claim amendments and arguments did not overcome the 35 USC 102 and 103 rejections for reasons set forth in the previous office action and herein below.
Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5 and 9-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BERTAIM et al.(WO 2012110537, English Machine translation is attached ).
Claim Interpretation: The examiner afforded the word intramammary its scientific literal meaning of anything situated or introduced within the mammary tissue or glands, specifically the breasts. This term is commonly used in veterinary medicine to describe the delivery of medication or other substances directly into the mammary gland of animals like dairy cows.
Regarding the limitations of claims 1-3, 5, and 9-10, BERTAIM et al. disclose a veterinary anti-prolactin composition to be administered to ruminants. Said composition includes at least one anti-prolactin compound which is an agonist for dopamine receptors and which is particularly useful for preventing and/or reducing the harmful effects in ruminants linked to use for a shortened dry period. Said composition is particularly useful for preventing and/or reducing metabolic diseases and/or reproductive disorders when lactation is resumed. The use of the veterinary anti-prolactin composition according to the invention does not adversely affect the milk-producing ability and/or the milk quality of the treated ruminants (see abstract). BERTAIM et al.disclose FIG. 3 is a graph illustrating the induction of the mRNA transcript corresponding to the long form of the prolactin receptor during the dry period and up to 90 days after calving in the group of cows injected with cabergoline (C646-1 and C646-2). BERTAIM et al.disclose in the detailed description of the invention section disclose veterinary compositions may be administered according to any route of administration well known in the art and adapted to the treatment of each animal. Preferably, they are administered by the cutaneous, oral, intramammary and parenteral routes. Even more preferably, they are administered parenterally, and in particular by intramuscular or subcutaneous injection. They may therefore be in the form of an oral, intramammary or injectable liquid solution or suspension, or in solid or semi-solid form, powders, tablets, capsules, granules, dragees, capsules. , sprays, cachets, pills, tablets, or pasta. BERTAIM et al. disclose in the detailed description of the invention section that the present invention relates to a veterinary composition comprising at least one antiprolactinic dopamine receptor agonist compound administered as a single treatment and/or repeated treatment during implementation and/or during the dry period, for its use in prevention and/or the reduction of deleterious effects associated with the implementation of a shortened dry period in ruminants. The present invention also relates to a veterinary composition comprising at least one antiprolactinic dopamine receptor agonist compound administered in a single treatment and / or in repeated treatment at the time of delivery. and / or during the dry period, for its use in the prevention and / or reduction of metabolic diseases and / or reproductive disorders of ruminants at the resumption of lactation. Among these antiprolactinic agonist compounds derived from rye ergot, mention may be made, for example, of cabergoline, metironoline, lisurdine, bromocriptine, ergometrine and all derivatives of these compounds having antiprolactinic activity. Cabergoline whose chemical name is N- [3- (Dimethylamino) propyl] -N- [(ethylamino) carbonyl] -6- (2-propenyl) -8g-ergoline-8-carboxamide, is a specific agonist antiprolactinic compound D2 receptors for dopamine. It is described in US Pat. No. 4,526,892. Its chemical formula developed is as follows: Cabergoline is the active ingredient in human drugs marketed under the names Dostinex® and 177 ®. Also, it is the basic active ingredient of the veterinary compositions marketed under the Galostop denomination for bitches subject to lactation of pseudogestation. Whether it is Dostinex® and Cabaser ®, these cabergoline-based compositions are never administered during pregnancy or pregnancy. Preferably, said veterinary compositions are administered to ruminants such as dairy cows, during the implementation of the dry period, as shown in Figure 1. The veterinary antiprolactinic compositions as well as the methods according to the present invention are attractive for the farmer since the latter can, by using them, reduce the duration of the dry period which will result in an increase in the milk production period, a management of the simplified herd as well as a saving on the costs of treating diseases at the resumption of lactation. As demonstrated in the examples below, a single and/or repeated treatment can be administered to ruminants during implementation and/or during the dry period, with a view to preventing and/or reducing metabolic diseases and diseases. reproductive disorders, and to improve the immune status and/or liver functions of ruminants upon resumption of lactation. For example, the veterinary compositions can be administered to dairy cows at the beginning of the dry period or during this dry period. Conventional dry periods are usually 8 weeks. Therefore, according to the present invention, shortened dry period means a dry period which is reduced by 1 week, or 2 weeks, or 3 weeks, or 4 weeks. Preferably, the shortened dry period is reduced compared to conventional dry periods of not more than 4 weeks, and even more preferably, it is reduced from 2 to 4 weeks. Therefore, according to the In the present invention, the conventional dry period of 8 weeks is reduced to a shortened dry period, the duration of which is preferably between 4 to 6 weeks. The veterinary compositions may be administered as single treatment and/or repeated during the implementation and/or during the dry period. The effective therapeutic quantities or doses may vary according to the ruminants to be treated and according to the method of administration of the compositions. Dosages, also called therapeutic regimens, can easily be determined by systematic tests based on the examples below and are within the abilities of those skilled in the art.
Regarding the limitations of claim 4, BERTAIM et al. disclose in description of the invention section that by way of examples, the effective therapeutic doses according to the present invention are between 1 and 100 mcg / kg, or between 5 and 50 mcg / kg, and preferably about 8 to 10 mcg / kg. In the case of dairy cows, it is possible to administer the compositions according to the invention during implementation and/or during the dry period, for example after the first 11 months of the annual cycle of the cow (Figure 1). According to the invention, ruminants are understood to mean herbivorous mammals such as, for example, cattle, sheep, goats, camelids, or cattle. The compositions according to the invention are administered to mammals producing milk ruminants, such as preferably cows and dairy ewes. BERTAIM et al.disclose in example 1 Preparation of Veterinary Compositions Based on Cabergoline
Step 1: 4.53 g of cabergoline and 1.5 kg of medium chain triglycerides were measured in a container of adequate capacity, then the mixture was stirred with a magnetic stirrer (500 rpm) for at least 60 minutes for complete dissolution.
Step 2: In a dry container, 5 kg of medium chain triglycerides were measured, the nitrogen flow and the mixer were started, then the concentrated solution cabergoline, obtained in step 1, was added in the container. Stirring was maintained for 30 minutes then the volume was brought to the final volume of 9 liters by adding medium chain triglycerides. Stirring was further maintained for 30 minutes and then the solution was filtered under pressurized nitrogen through a cartridge calibrated at 0.45 microns. The filtrate was collected in a suitable drum previously disinfected with steam and dried with a stream of nitrogen. The resulting solution was sterilized at 121 ° C for 15 minutes, then dispensed into sterile, pyrogen-free flasks closed with rubber stoppers and aluminum caps, washed and autoclaved.
BERTAIM et al. disclose the carbergoline veterinary composition is an injectable oily solution of cabergoline as described in Example 1. It is administered by intramuscular injection into the neck at a dose of 5.6 mg/cow or about 8 mcg/kg.
BERTAIM et al. disclose a veterinary composition characterized in that it comprises at least one compound having an antiprolactinic dopamine receptor agonist activity for its use in preventing and / or reducing the deleterious effects associated with the implementation of a shortened dry period in ruminants (claim 1). Veterinary composition according to claim 8, characterized in that the agonist compounds derived from the ergot of rye are chosen in particular from cabergoline, metergoline, lisurdine, bromocriptine, ergometrine, and / or a derivative of those (claim 9). Composition according to any one of the preceding claims, characterized in that said composition is administered parenterally, intramammary, cutaneous or oral (see claim 12). Composition according to any one of the preceding claims, characterized in that said composition is administered by injection (claim 13).
With regard to the preamble reciting “A method for reducing milk production of a dairy ruminant” BERTAIM et al. disclose exactly the same method step of administering a dairy cow with a veterinary composition comprising cabergoline via intramammary route. Therefore, “A method for reducing milk production of a dairy ruminant” would inherently happen. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP § 2112.01 with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103.
Response to Arguments
Applicant's arguments filed 11 December 2025 have been fully considered but they are not persuasive.
Applicant argues Bertaim et al. neither discloses nor inherently teaches such an effect. The express teaching of Bertaim that the milk-producing capacity is not affected contradicts the claimed method, which specifically achieves a reduction in milk production. The Office Action appears to rely on an alleged inherent effect of intramammary administration in Bertaim et al. to meet the claimed limitation of reducing milk production. However, inherency requires that the claimed feature be necessarily and inevitably present in the prior-art disclosure, not merely possible or probable. /n re Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999); MEHL/Bijophile Int'l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999): Schering Corp. v. Geneva Pharm., Inc., 339 F.3d 1373, 1377 (Fed. Cir. 2003). As confirmed in /n re Oelrich, 666 F.2d 578, 581 (CCPA 1981), a characteristic is inherent only when it is “necessarily present in the thing described.” Here, Bertaim et al. explicitly states that its cabergoline compositions do not affect milk production, which directly contradicts the Office Action’s assertion of inherency. Because the alleged effect is neither inevitable nor expressly disclosed, the rejection under § 102 cannot be sustained. Moreover, the examples of Bertaim do not involve intramammary administration, and no disclosure in the reference demonstrates or implies that intramammary administration of cabergoline would result in reduced milk production. Accordingly, the Examiner’s position that this effect is inherently obtained is unsupported. A skilled person would not understand from Bertaim that intramammary delivery inherently or necessarily causes milk reduction; rather, the teaching is the opposite.
The above assertions are not found persuasive because the examiner maintains that BERTAIM et al. disclose exactly the same method step of administering a dairy cow with a veterinary composition comprising cabergoline via intramammary route. Therefore, “A method for reducing milk production of a dairy ruminant” would inherently happen. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP § 2112.01 with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103. Contrary to Applicant’s assertions in a method claim the most important element is the specific step recited which in the instant case is a method step of administering a dairy cow with a veterinary composition comprising cabergoline via intramammary route. BERTAIM et al. disclose exactly the same method step of administering a dairy cow with a veterinary composition comprising cabergoline via intramammary route. Therefore, “A method for reducing milk production of a dairy ruminant” would inherently happen. Additionally, BERTAIM et al. disclose a veterinary anti-prolactin composition to be administered to ruminants. Said composition includes at least one anti-prolactin compound which is an agonist for dopamine receptors and which is particularly useful for preventing and/or reducing the harmful effects in ruminants linked to use for a shortened dry period. Said composition is particularly useful for preventing and/or reducing metabolic diseases and/or reproductive disorders when lactation is resumed. The use of the veterinary anti-prolactin composition according to the invention does not adversely affect the milk-producing ability and/or the milk quality of the treated ruminants (see abstract). The examiner reminds Applicant that as it is conventionally known Prolactin (PRL) is a crucial protein hormone from the pituitary gland, primarily known for stimulating breast development and milk production (lactation) after childbirth. As described above BERTAIM et al. disclose a veterinary anti-prolactin composition which entails a composition that will inhibit prolactin which eventually result in the reduction of milk production. It must be also noted that BERTAIM et al. disclose that the use of the veterinary anti-prolactin composition according to the invention does not adversely affect the milk-producing ability and/or the milk quality of the treated ruminants (see abstract). The alternative entails that veterinary anti-prolactin composition does not adversely affect the milk quality of the treated ruminants. Additionally, the examiner reminds Applicant that the meaning of “the veterinary anti-prolactin composition according to the invention does not adversely affect the milk-producing ability” is not necessarily related to the quantity of milk to be produced but the ability of the animal to produce milk. Therefore, BERTAIM et al. indeed anticipates the currently claimed limitations for reasons set forth in the previous office action and herein above.
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.
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.
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 1-10 remain rejected under 35 U.S.C. 103 as being unpatentable over BERTAIM et al.(WO 2012110537, English Machine translation is attached ) and Hop et al. (J. Dairy Sci. 102:11670–11680, 2019).
Applicants’ claims
Applicants claim a method for reducing milk production of a dairy ruminant, wherein a veterinary composition comprising cabergoline is administered in therapeutically effective amount to said dairy ruminant by intramammary route.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Claim Interpretation: The examiner afforded the word intramammary its scientific literal meaning of anything situated or introduced within the mammary tissue or glands, specifically the breasts. This term is commonly used in veterinary medicine to describe the delivery of medication or other substances directly into the mammary gland of animals like dairy cows.
Regarding the limitations of claims 1-3, 5, and 9-10, BERTAIM et al. teach a veterinary anti-prolactin composition to be administered to ruminants. Said composition includes at least one anti-prolactin compound which is an agonist for dopamine receptors and which is particularly useful for preventing and/or reducing the harmful effects in ruminants linked to use for a shortened dry period. Said composition is particularly useful for preventing and/or reducing metabolic diseases and/or reproductive disorders when lactation is resumed. The use of the veterinary anti-prolactin composition according to the invention does not adversely affect the milk-producing ability and/or the milk quality of the treated ruminants (see abstract). BERTAIM et al. teach FIG. 3 is a graph illustrating the induction of the mRNA transcript corresponding to the long form of the prolactin receptor during the dry period and up to 90 days after calving in the group of cows injected with cabergoline (C646-1 and C646-2). BERTAIM et al. teach in the detailed description of the invention section disclose veterinary compositions may be administered according to any route of administration well known in the art and adapted to the treatment of each animal. Preferably, they are administered by the cutaneous, oral, intramammary and parenteral routes. Even more preferably, they are administered parenterally, and in particular by intramuscular or subcutaneous injection. They may therefore be in the form of an oral, intramammary or injectable liquid solution or suspension, or in solid or semi-solid form, powders, tablets, capsules, granules, dragees, capsules. , sprays, cachets, pills, tablets, or pasta. BERTAIM et al. teach in the detailed description of the invention section that the present invention relates to a veterinary composition comprising at least one antiprolactinic dopamine receptor agonist compound administered as a single treatment and/or repeated treatment during implementation and/or during the dry period, for its use in prevention and/or the reduction of deleterious effects associated with the implementation of a shortened dry period in ruminants. The present invention also relates to a veterinary composition comprising at least one antiprolactinic dopamine receptor agonist compound administered in a single treatment and / or in repeated treatment at the time of delivery. and / or during the dry period, for its use in the prevention and / or reduction of metabolic diseases and / or reproductive disorders of ruminants at the resumption of lactation. Among these antiprolactinic agonist compounds derived from rye ergot, mention may be made, for example, of cabergoline, metironoline, lisurdine, bromocriptine, ergometrine and all derivatives of these compounds having antiprolactinic activity. Cabergoline whose chemical name is N- [3- (Dimethylamino) propyl] -N- [(ethylamino) carbonyl] -6- (2-propenyl) -8g-ergoline-8-carboxamide, is a specific agonist antiprolactinic compound D2 receptors for dopamine. It is described in US Pat. No. 4,526,892. Its chemical formula developed is as follows: Cabergoline is the active ingredient in human drugs marketed under the names Dostinex® and Cabaser ®. Also, it is the basic active ingredient of the veterinary compositions marketed under the Galostop denomination for bitches subject to lactation of pseudogestation. Whether it is Dostinex® and Cabaser ®, these cabergoline-based compositions are never administered during pregnancy or pregnancy. Preferably, said veterinary compositions are administered to ruminants such as dairy cows, during the implementation of the dry period, as shown in Figure 1. The veterinary antiprolactinic compositions as well as the methods according to the present invention are attractive for the farmer since the latter can, by using them, reduce the duration of the dry period which will result in an increase in the milk production period, a management of the simplified herd as well as a saving on the costs of treating diseases at the resumption of lactation. As demonstrated in the examples below, a single and/or repeated treatment can be administered to ruminants during implementation and/or during the dry period, with a view to preventing and/or reducing metabolic diseases and diseases. reproductive disorders, and to improve the immune status and/or liver functions of ruminants upon resumption of lactation. For example, the veterinary compositions can be administered to dairy cows at the beginning of the dry period or during this dry period. Conventional dry periods are usually 8 weeks. Therefore, according to the present invention, shortened dry period means a dry period which is reduced by 1 week, or 2 weeks, or 3 weeks, or 4 weeks. Preferably, the shortened dry period is reduced compared to conventional dry periods of not more than 4 weeks, and even more preferably, it is reduced from 2 to 4 weeks. Therefore, according to the In the present invention, the conventional dry period of 8 weeks is reduced to a shortened dry period, the duration of which is preferably between 4 to 6 weeks. The veterinary compositions may be administered as single treatment and/or repeated during the implementation and/or during the dry period. The effective therapeutic quantities or doses may vary according to the ruminants to be treated and according to the method of administration of the compositions. Dosages, also called therapeutic regimens, can easily be determined by systematic tests based on the examples below and are within the abilities of those skilled in the art.
Regarding the limitations of claim 4, BERTAIM et al. teach in description of the invention section that by way of examples, the effective therapeutic doses according to the present invention are between 1 and 100 mcg / kg, or between 5 and 50 mcg / kg, and preferably about 8 to 10 mcg / kg. In the case of dairy cows, it is possible to administer the compositions according to the invention during implementation and/or during the dry period, for example after the first 11 months of the annual cycle of the cow (Figure 1). According to the invention, ruminants are understood to mean herbivorous mammals such as, for example, cattle, sheep, goats, camelids, or cattle. The compositions according to the invention are administered to mammals producing milk ruminants, such as preferably cows and dairy ewes. BERTAIM et al. teach in example 1 Preparation of Veterinary Compositions Based on Cabergoline
Step 1: 4.53 g of cabergoline and 1.5 kg of medium chain triglycerides were measured in a container of adequate capacity, then the mixture was stirred with a magnetic stirrer (500 rpm) for at least 60 minutes for complete dissolution.
Step 2: In a dry container, 5 kg of medium chain triglycerides were measured, the nitrogen flow and the mixer were started, then the concentrated solution cabergoline, obtained in step 1, was added in the container. Stirring was maintained for 30 minutes then the volume was brought to the final volume of 9 liters by adding medium chain triglycerides. Stirring was further maintained for 30 minutes and then the solution was filtered under pressurized nitrogen through a cartridge calibrated at 0.45 microns. The filtrate was collected in a suitable drum previously disinfected with steam and dried with a stream of nitrogen. The resulting solution was sterilized at 121 ° C for 15 minutes, then dispensed into sterile, pyrogen-free flasks closed with rubber stoppers and aluminum caps, washed and autoclaved.
BERTAIM et al. teach the carbergoline veterinary composition is an injectable oily solution of cabergoline as described in Example 1. It is administered by intramuscular injection into the neck at a dose of 5.6 mg/cow or about 8 mcg/kg.
BERTAIM et al. teach a veterinary composition characterized in that it comprises at least one compound having an antiprolactinic dopamine receptor agonist activity for its use in preventing and / or reducing the deleterious effects associated with the implementation of a shortened dry period in ruminants (claim 1). Veterinary composition according to claim 8, characterized in that the agonist compounds derived from the ergot of rye are chosen in particular from cabergoline, metergoline, lisurdine, bromocriptine, ergometrine, and / or a derivative of those (claim 9). Composition according to any one of the preceding claims, characterized in that said composition is administered parenterally, intramammary, cutaneous or oral (see claim 12). Composition according to any one of the preceding claims, characterized in that said composition is administered by injection (claim 13).
Additionally, with regard to the preamble reciting “A method for reducing milk production of a dairy ruminant” BERTAIM et al. teach exactly the same method step of administering a dairy cow with a veterinary composition comprising cabergoline via intramammary route. Therefore, “A method for reducing milk production of a dairy ruminant” would inherently happen. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP § 2112.01 with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
BERTAIM et al. teach the amount of cabergoline recited in claims 7-8 in overlapping manner. BERTAIM et al. do not specifically teach wherein the composition is administered to all quarters of the mammary gland of the ruminant. These deficiencies are cured by the teachings of Hop et al.
Hop et al. teach the abrupt cessation of milking at dry-off may induce milk leakage, which may increase the risk of new intramammary infections (IMI). This study assessed the efficacy of 1 i.m. injection of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France) at drying-off on milk leakage after dry-off and new IMI across the dry period and postcalving compared with a placebo (negative control) and an intramammary antibiotic treatment (positive control) under field conditions. The study was a double-blind, randomized, 3-arm, multicenter, clinical trial performed under Good Clinical Practice conditions. Data from 900 dairy cows of various breeds from 63 farms in France, Germany, and Hungary were analyzed. Only quarters with no bacterial growth at drying-off and a cow somatic cell count ≤200,000 cells/mL were included. Quarters infected with major or minor pathogens or cows with high somatic cell count at time of inclusion were excluded. Cows that qualified for the study were visited 7 times in total before and after drying-off and after calving. Presence (yes/no) of milk leakage was recorded on the day after dry-off. A new infected quarter (new IMI) was defined as one with a major pathogen present in any one of the 2 postcalving samples. Two mixed logistic regression models were fitted to the data to evaluate the efficacy of cabergoline in the reduction of milk leakage and new IMI. One i.m. injection of cabergoline at drying-off significantly reduced the incidence of milk leakage the day after dry-off compared with both placebo and antibiotic treatment. Cabergoline treated cows significantly reduced the risk of new IMI by major pathogens across the dry period and postcalving by 21% when compared with placebo cows (20.5 vs 26.0%, respectively). However, when milk leakage was added to the model, the significance of cabergoline was reduced. We interpreted this to show that milk leakage is an intervening variable between treatment with cabergoline and lower risk of new IMI. The antibiotic treatment significantly decreased the odds of new IMI compared with both cabergoline and placebo. However, because several countries are currently disallowing the preventive use of antibiotics at dry-off in noninfected quarters, the dry-off facilitator cabergoline may therefore be of particular value to reduce the risk of new IMI across the dry period (see abstract).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill before the effective filing date of the instant invention to modify the teachings of BERTAIM et al. by applying the composition to all quarters of the mammary gland of the ruminant because Hop et al. teach the abrupt cessation of milking at dry-off may induce milk leakage, which may increase the risk of new intramammary infections (IMI). This study assessed the efficacy of 1 i.m. injection of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France) at drying-off on milk leakage after dry-off and new IMI across the dry period and postcalving compared with a placebo (negative control) and an intramammary antibiotic treatment (positive control) under field conditions. The study was a double-blind, randomized, 3-arm, multicenter, clinical trial performed under Good Clinical Practice conditions. Data from 900 dairy cows of various breeds from 63 farms in France, Germany, and Hungary were analyzed. Only quarters with no bacterial growth at drying-off and a cow somatic cell count ≤200,000 cells/mL were included. Quarters infected with major or minor pathogens or cows with high somatic cell count at time of inclusion were excluded. Cows that qualified for the study were visited 7 times in total before and after drying-off and after calving. Presence (yes/no) of milk leakage was recorded on the day after dry-off. A new infected quarter (new IMI) was defined as one with a major pathogen present in any one of the 2 postcalving samples (abstract). One of ordinary skill in the art would have been motivated to do so because Hop et al. teach that two mixed logistic regression models were fitted to the data to evaluate the efficacy of cabergoline in the reduction of milk leakage and new IMI. One i.m. injection of cabergoline at drying-off significantly reduced the incidence of milk leakage the day after dry-off compared with both placebo and antibiotic treatment. Cabergoline treated cows significantly reduced the risk of new IMI by major pathogens across the dry period and postcalving by 21% when compared with placebo cows (20.5 vs 26.0%, respectively). However, when milk leakage was added to the model, the significance of cabergoline was reduced. We interpreted this to show that milk leakage is an intervening variable between treatment with cabergoline and lower risk of new IMI. The antibiotic treatment significantly decreased the odds of new IMI compared with both cabergoline and placebo. However, because several countries are currently disallowing the preventive use of antibiotics at dry-off in noninfected quarters, the dry-off facilitator cabergoline may therefore be of particular value to reduce the risk of new IMI across the dry period (see abstract). The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol. "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).
A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of BERTAIM et al. and Hop et al. because both references teach cabergoline based antiprolactinic compositions. Furthermore, in the case where the claimed amounts or doses of active "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). Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11 December 2025 have been fully considered but they are not persuasive.
Applicant argues as discussed above, Bertaim et al. discloses administration of cabergoline to mitigate the adverse effects of a shortened dry period, and explicitly states that the compositions used do not affect milk production. There is no suggestion that intramammary administration, though generally mentioned among possible routes, would have any effect on milk yield, let alone reduce it. Hop et al., cited as a secondary reference, does not cure these deficiencies. Nothing in Hop et al. discloses or suggests that intramammary administration of cabergoline, or any related dopaminergic compound, would result in a reduction in milk production. A person of ordinary skill in the art would therefore have had no motivation to select the intramammary route from among the many administration routes generically listed in Bertaim et al., nor any reasonable expectation of success that doing so would lead to the opposite effect: i.e., a reduction in milk production, of what Bertaim explicitly describes. The claimed method thus represents a non-obvious and unexpected result, arising specifically from the unique route of administration defined in the claims.
The above assertions are not found persuasive for the same reasons set forth in the previous office action and for the same reasons described above in the response to arguments section regarding the 35 USC 102 rejections which are incorporated herein by reference. It would have been prima facie obvious to a person of ordinary skill before the effective filing date of the instant invention to modify the teachings of BERTAIM et al. by applying the composition to all quarters of the mammary gland of the ruminant because Hop et al. teach the abrupt cessation of milking at dry-off may induce milk leakage, which may increase the risk of new intramammary infections (IMI). This study assessed the efficacy of 1 i.m. injection of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France) at drying-off on milk leakage after dry-off and new IMI across the dry period and postcalving compared with a placebo (negative control) and an intramammary antibiotic treatment (positive control) under field conditions. The study was a double-blind, randomized, 3-arm, multicenter, clinical trial performed under Good Clinical Practice conditions. Data from 900 dairy cows of various breeds from 63 farms in France, Germany, and Hungary were analyzed. Only quarters with no bacterial growth at drying-off and a cow somatic cell count ≤200,000 cells/mL were included. Quarters infected with major or minor pathogens or cows with high somatic cell count at time of inclusion were excluded. Cows that qualified for the study were visited 7 times in total before and after drying-off and after calving. Presence (yes/no) of milk leakage was recorded on the day after dry-off. A new infected quarter (new IMI) was defined as one with a major pathogen present in any one of the 2 postcalving samples (abstract). One of ordinary skill in the art would have been motivated to do so because Hop et al. teach that two mixed logistic regression models were fitted to the data to evaluate the efficacy of cabergoline in the reduction of milk leakage and new IMI. One i.m. injection of cabergoline at drying-off significantly reduced the incidence of milk leakage the day after dry-off compared with both placebo and antibiotic treatment. Cabergoline treated cows significantly reduced the risk of new IMI by major pathogens across the dry period and postcalving by 21% when compared with placebo cows (20.5 vs 26.0%, respectively). However, when milk leakage was added to the model, the significance of cabergoline was reduced. We interpreted this to show that milk leakage is an intervening variable between treatment with cabergoline and lower risk of new IMI. The antibiotic treatment significantly decreased the odds of new IMI compared with both cabergoline and placebo. However, because several countries are currently disallowing the preventive use of antibiotics at dry-off in noninfected quarters, the dry-off facilitator cabergoline may therefore be of particular value to reduce the risk of new IMI across the dry period (see abstract). The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol. "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).
A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of BERTAIM et al. and Hop et al. because both references teach cabergoline based antiprolactinic compositions. Furthermore, in the case where the claimed amounts or doses of active "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). Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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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/TIGABU KASSA/Primary Examiner, Art Unit 1619