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 .
Applicant’s reply has overcome the objection to the specification.
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 and 3-9 are rejected under 35 U.S.C. 103 as being unpatentable over Burnam (WO 2016/204959) and Hahn et al. (WO 2022186661, Espacenet English translation provided). All references of record.
In claim 10, Burnam claims a process for preparing a petrolatum-based composition comprising
a) providing an active ingredient in a liquid solution;
b) heating the petrolatum to a temperature sufficient to cause the petrolatum to melt
to give a melted petrolatum;
c) heating the active ingredient solution to a temperature higher than the temperature of the melted petrolatum to give a heated active ingredient solution;
d) mixing the melted petrolatum and the heated active ingredient solution to give a
melted mixture; and
e) cooling the melted mixture to give the petrolatum-based composition.
Regarding the temperatures recited in step b) of instant claims 8 and 9, paragraph [0026], Burnam teaches that the petrolatum is heated from about 37 degrees Celsius to about 40 degrees Celsius. Regarding the temperatures recited in step c) of instant claim 9, claim 13 of Burnam recites that the heated active ingredient solution has a temperature that is about 1 °C to about 5°C higher than the temperature of the melted petrolatum. Paragraph [0029] teaches that the cooling, corresponding to step (e), is gradually decreased to ambient temperatures, as required in step (e) of claims 8 and 9. On page 3, lines 1-2, Burnam teaches that the petrolatum-based composition is greater than about 80%, as required by instant claim 1. Claim 1 of Burnam recites that the active ingredient is dispersed as nanodroplets throughout the petrolatum, as required by instant claim 3.
Regarding the medical effectiveness when the composition of Burnam is stored at a temperature of about 4°C for 28 days, as recited in instant claim 6 or after exposure to ambient temperatures for 14 days following temperature-controlled storage, paragraph [0016] of Burnam teaches the stability of nanodroplets comprising the active agents is shelf-stable and is resistant to degradation for two years. Also see Example 18, describing accelerated temperature stability testing, exceeding the parameters recited in claims 6 and 7.
Claim 14 of Burnam recite that the active agent is a biologic, including glycoproteins (10 lines up from the last on page 10); proteins ((6 lines up from the last on page 14). Example 6, bridging pages 33-35 describes mixing liquid suspensions of Methicillin-resistant
Staphylococcus aureus (MRSA), T. rubrum, and Staphylococcus Epidermidis, respectively, in antimicrobial Formulation 1 comprising 95% petrolatum; 0.13% BZK, 0.2% PHMB, and 4.67% water in Example 1 in paragraph [0041]. Paragraphs [0009-0010] describe Figures 3 and 4, depicting graphs showing the reduction of MRSA and T. rubrum, respectively, in the presence of Formulation 1 in the suspension time-kill procedure.
However, Burnam does not teach mixing a mucosal vaccine comprising an live, attenuated or inactivated vaccine or a subunit vaccine, with the petrolatum, as required in instant claims 1, 4, and 5 or heating the active ingredient solution to a temperature equal to or less than the temperature of the melted petrolatum to give a heated active ingredient solution, as recited in instant claim 8(c).
Paragraphs [0075 and 0076] of Hahn et al. teach a pharmaceutical composition containing (i) an porcine Mycoplasma hyopneumoniae (Mhp) strain (inactivated in claim 8); (ii) a porcine Mycoplasma hyorhinis (Mhr) strain (inactivated in claim 9); (iii) porcine Mycoplasma hyopneumoniae-derived recombinant P97 protein; and (iv) a porcine circovirus type 2 (PCV2)-derived recombinant protein actively suspended or dissolved in the carrier comprising petrolatum for rectal administration (defined as a mucosal surface in instant paragraph [0013]).
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have mixed the mucosal vaccine of Hahn et al. with the petrolatum pharmaceutical formulation of Burnam to prevent pigs against Mhp, Mrh, and PCV2 infections, see claim 14 of Hahn et al. One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have mixed the mucosal vaccine of Hahn et al. with the petrolatum pharmaceutical formulation of Burnam because Burnam teaches the petrolatum-based compositions are non-irritating, nontoxic, and the nanodroplets release the active ingredients to the application site continuously, see paragraph [0004]. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have mixed the mucosal vaccine of Hahn et al. with the petrolatum pharmaceutical formulation of Burnam because both Hahn et al. and Barnum teach mixing the active ingredients with the petrolatum carrier, see paragraph [0075] of Hahn et al. and claim 10 of Burnam.
Response to Arguments
Applicant states that the disclosed compositions and methods have surprisingly been discovered to increase the stability, particularly the thermal stability, of liquid mucosal vaccines which may be stored in cold storage or at ambient conditions prior to administration to a subject, without an accompanying loss in vaccine effectiveness or potency. Applicant asserts that the stability described in Burnam is limited to whether the active ingredients or nanodroplets separate from the petrolatum, rather than having anything to do with enhanced thermostability and vaccine viability following storage or temperature excursions, referencing paragraph [0016].
Applicant additionally asserts that the instant methods and compositions may further provide for mucosal vaccine delivery with substantially less transfer loss and with greater dosing predictability, as a result of increased contact duration of time over which the vaccine may be taken up by the mucosal site.
Applicant’s arguments have been fully considered, but are found unpersuasive because the attributes of stability during storage and extended medicinal release is appreciated by Burnam. Paragraph [0010] of Burnam. states that the compositions made by the claimed process are shelf stable for extended periods of time even under non-ideal conditions. Paragraph [0016] of Burnam teaches the stability of nanodroplets comprising the active agents is shelf-stable and is resistant to degradation for two years. “Even under accelerated conditions, such as reduced pressure, the petrolatum and the active ingredients do not separate.” Therefore, the message conveyed by Burnam in paragraph [0016] pertains to the “integrity of the composition as a whole”, which includes petrolatum and “the active ingredients”, which remain active due to the “extensive chemical stability for the active ingredient” during storage for at least two years. Also see Example 18, describing accelerated temperature stability testing, exceeding the parameters recited in instant claims 6 and 7. Burnam teaches the petrolatum-based compositions are non-irritating, nontoxic, and the nanodroplets release the active ingredients to the application site continuously for up to one week, see paragraphs [0004, 0037, and 0038].
Applicant argues that the active ingredients in Burnam are small molecule pharmaceutically active ingredients and cationic biocides and points to paragraphs [0019, 0020, 0041-0127] and Examples 1-19 and 21.
Applicant’s arguments have been fully considered, but are found unpersuasive. Claim 14 of Burnam recite that the active agent is a biologic, including glycoproteins (10 lines up from the last on page 10); proteins ((6 lines up from the last on page 14). Example 6, bridging pages 33-35 describes mixing liquid suspensions of Methicillin-resistant Staphylococcus aureus (MRSA), T. rubrum, and Staphylococcus Epidermidis, respectively, in antimicrobial Formulation 1 comprising 95% petrolatum; 0.13% BZK, 0.2% PHMB, and 4.67% water in Example 1 in paragraph [0041]. Paragraphs [0009-0010] describe Figures 3 and 4, depicting graphs showing the reduction of MRSA and T. rubrum, respectively, in the presence of Formulation 1 in the suspension time-kill procedure. The antigen encompassed by instant claims 1 and 4 include inactivated, subunit, and toxoid compositions corresponding to the glycoproteins, proteins, and antimicrobial liquid suspension comprising MRSA, T. rubrum, and Staphylococcus
epidermidis taught by Burnam on pages 10, 14, and Example 6. The intended use of the claimed materials as a vaccine is indistinguishable from the same materials taught by Burnam.
Applicant criticizes the teachings of Hahn et al. as mentioning “white petrolatum” in a single instance as one of several potential carriers that may be used in an ointment applied topically to the skin.
Applicant’s arguments have been fully considered, but are found unpersuasive. In the instant case, Hahn et al. teach mixing the active vaccine ingredients with the white petrolatum carrier in paragraph [0075]. “[T]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004) and MPEP § 2143.01 (I).
Applicant argues that one of ordinary skill in the art at the time of the invention would not understand Hahn to teach that rectal administration of the pharmaceutical composition would involve suspension in a carrier described earlier in the paragraph with respect to topical application to the skin.
Applicant’s arguments and a review of the teachings of Hahn et al. have been fully considered, but are found unpersuasive. The sequence of teachings by Hahn et al. follow a cohesive narrative regarding pharmaceutical applicability and effective pharmaceutical carriers. Paragraph [0075], begins with, “The pharmaceutical composition of the present invention can also be administered in the form of a suppository for rectal administration.” This teaching is followed by a list of suitable carriers for topical administration of the vaccine component mixture, including white petrolatum. The next to the last sentence in paragraph [0076] states that topical administration includes rectal suppositories. Therefore, the ordinary artisan would not be required to leap from one concept to another to understand the fluid teachings presented in two sequential paragraphs of Hahn et al.
Applicant argues that Hahn also fails to specifically teach or suggest a thermostable vaccine composition comprising at least 80% by weight petrolatum or a method for preparing a vaccine composition comprising petrolatum for intranasal or mucosal administration, as recited in amended claim 1. Applicant points out that there is no teaching or suggestion in Hahn that petrolatum may be used as a carrier for a vaccine composition in order to produce a vaccine composition having increased thermal stability or to produce a composition that provides for greater dose transfer and dosing predictability.
Applicant’s arguments have been fully considered, but are found unpersuasive. Hahn et al. is not required to satisfy the limitations already taught by Burnam.
In claim 10, Burnam claims a process for preparing a petrolatum-based composition comprising
a) providing an active ingredient in a liquid solution;
b) heating the petrolatum to a temperature sufficient to cause the petrolatum to melt
to give a melted petrolatum;
c) heating the active ingredient solution to a temperature higher than the temperature of the melted petrolatum to give a heated active ingredient solution;
d) mixing the melted petrolatum and the heated active ingredient solution to give a
melted mixture; and
e) cooling the melted mixture to give the petrolatum-based composition.
On page 3, lines 1-2, Burnam teaches that the petrolatum-based composition is greater than about 80%, as required by instant claim 1. Claim 1 of Burnam recites that the active ingredient is dispersed as nanodroplets throughout the petrolatum, as required by instant claim 3.
Regarding the medical effectiveness when the composition of Burnam is stored at a temperature of about 4°C for 28 days, as recited in instant claim 6 or after exposure to ambient temperatures for 14 days following temperature-controlled storage, paragraph [0016] of Burnam teaches the stability of nanodroplets comprising the active agents is shelf-stable and is resistant to degradation for two years. Also see Example 18, describing accelerated temperature stability testing, exceeding the parameters recited in claims 6 and 7. Also, if Hahn et al. had taught a method of preparing a thermostable vaccine composition comprising at least 80% by weight petrolatum for intranasal or mucosal administration, the reference would have been considered under an anticipatory statute.
Applicant argues that all of the working examples in Hahn are directed to parenteral injection of the composition. The brief mentions of intranasal administration in Hahn are directed to nasal aerosol or inhalation or to injection into the nasal passage of a pig (see Hahn at Example 7-1), rather than in the form of a thermostable vaccine composition comprising at least 80% by weight petrolatum, as recited in amended claim 1.
Applicant’s arguments have been fully considered, but are found unpersuasive. “[T]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004) and MPEP § 2143.01 (I). Paragraphs [0075 and 0076] of Hahn et al. teach a pharmaceutical composition containing (i) an porcine Mycoplasma hyopneumoniae (Mhp) strain (inactivated in claim 8); (ii) a porcine Mycoplasma hyorhinis (Mhr) strain (inactivated in claim 9); (iii) porcine Mycoplasma hyopneumoniae-derived recombinant P97 protein; and (iv) a porcine circovirus type 2 (PCV2)-derived recombinant protein actively suspended or dissolved in the carrier comprising petrolatum for rectal administration (defined as a mucosal surface in instant paragraph [0013]).
Applicant argues that there is no teaching or suggestion in Hahn that petrolatum may be used as a carrier for a vaccine composition in order to produce a vaccine composition having increased thermal stability or to produce a composition that provides for greater dose transfer and dosing predictability.
Applicant’s arguments have been fully considered, but are found unpersuasive. The attributes of stability during storage and extended medicinal release is appreciated by Burnam. Paragraph [0010] of Burnam. states that the compositions made by the claimed process are shelf stable for extended periods of time even under non-ideal conditions. Paragraph [0016] of Burnam teaches the stability of nanodroplets comprising the active agents is shelf-stable and is resistant to degradation for two years. “Even under accelerated conditions, such as reduced pressure, the petrolatum and the active ingredients do not separate.” Therefore, the message conveyed by Burnam in paragraph [0016] pertains to the “integrity of the composition as a whole”, which includes petrolatum and “the active ingredients”, which remain active due to the “extensive chemical stability for the active ingredient” during storage for at least two years. Also see Example 18, describing accelerated temperature stability testing, exceeding the parameters recited in instant claims 6 and 7. Burnam teaches the petrolatum-based compositions are non-irritating, nontoxic, and the nanodroplets release the active ingredients to the application site continuously for up to one week, see paragraphs [0004, 0037, and 0038].
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have mixed the mucosal vaccine of Hahn et al. with the petrolatum pharmaceutical formulation of Burnam to prevent pigs against Mhp, Mrh, and PCV2 infections, see claim 14 of Hahn et al. One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have mixed the mucosal vaccine of Hahn et al. with the petrolatum pharmaceutical formulation of Burnam because Burnam teaches the petrolatum-based compositions are non-irritating, nontoxic, and the nanodroplets release the active ingredients to the application site continuously, see paragraph [0004]. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have mixed the mucosal vaccine of Hahn et al. with the petrolatum pharmaceutical formulation of Burnam because both Hahn et al. and Barnum teach mixing the active ingredients with the petrolatum carrier, see paragraph [0075] of Hahn et al. and claim 10 of Burnam.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date, absent unexpected results to the contrary.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
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/Shanon A. Foley/ Primary Examiner, Art Unit 1671