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 .
2. Applicant’s amendment filed on 04/14/2026 is acknowledged.
3. Claims 1-20 are pending and under consideration.
4. Applicant’s IDS document filed on 06/30/2026 has been considered.
5. The following rejection is necessitated by the amendment filed on 04/14/2026.
6. 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.
7. 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.
8. Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over the Pollinex Grasses and Rye Technical User Leaflet (PTO-892; Reference U) in view of Zielen et al. (PTO-892 mailed on 01/16/2026; Page 2; Reference U) and Heath et al. (PTO-892 mailed on 01/16/2026; Page 2; Reference V) as evidenced by Shardlow et al. (PTO-892 mailed on 01/16/2026; Reference W) and Hopkins et al. (PTO-892 mailed on 01/16/2026; Reference X).
The Pollinex Grasses and Rye technical leaflet teaches a kit comprising 6 doses in 4 vials: the first dose being 600 SU in 1ml vial, the second dose being 1600 SU in 1 ml vial, the third dose being 4000 SU in 1 ml vial, followed by the “extension course” which is 3 doses in a 1.5 ml vial the fourth dose being 2000 SU, the fifth dose being 2000 SU and the sixth dose being 2000 SU. The reference teaches the list of excipients are L-Tyrosine, Liquefied Phenol, Sodium Chloride Disodium Phosphate Dodecahydrate, Sodium Dihydrogen Phosphate Dihydrate, Glycerol and Water for Injections (In particular, page 6, whole document)
The Pollinex Grasses and Rye technical leaflet teaches that the method of administration by subcutaneous injection for children 6 an over, adolescents and adults comprising administering 6 doses in the following way:
the first dose being 300 SU in .5 ml followed by an interval of 7-14 days
the second dose being 800 SU in .5 ml followed by an interval of 7-14 days,
the third dose being 2000 SU in .5 ml followed by an interval of
14 days,
beginning the “extension course” which provides for the fourth dose being 2000 SU in .5 ml followed by an interval of 2-4 weeks;
the fifth dose being 2000 SU in .5 ml followed by an interval of 2-4 weeks; and
the sixth dose being 2000 SU in .5ml.
“The injections should be given at intervals of 7-14 days. Treatment is to be initiated with 0.5 ml of vial/syringe No. 1, followed 7-14 days later by 0.5 ml of vial/syringe No. 2 and finally 7-14 days later by 0.5 ml of vial/syringe No. 3, in accordance with the dosage regimen above. The Extension Course consists of three injections of the maximum dose of 2000 SU/0.5 ml. The first injection of 0.5 ml should be given 14 days after the last injection of POLLINEX Grasses and Rye. Subsequent injections should then be given at intervals of 2-4 weeks. If the season is imminent, the interval can be reduced to 1 week. The course should be completed before the onset of the grass pollen season.” (In particular, pages 1-2 whole document).
POLLINEX Grasses + Rye contains equal proportions of 13 selectively purified allergen extracts of pollen from the following grasses: Foxtail (Alopecurus pratensis), Crested Dogstail (Cynosurus cristatus), Cocksfoot (Dactylis glomerata), Rye grass (Lolium perenne), Meadow grass (Poa pratensis), Vernal (Anthoxanthum odoratum), Fescue (Festuca pratensis), Bent (Agrostis tenuis), Timothy (Phleum pratense), Brome (Bromus spp.), Oat grass (Arrhenatherum elatius) and Yorkshire Fog (Holcus lanatus) and Cultivated Rye (Secale cereale) The allergens have been converted into allergoids by treatment with glutaraldehyde and are adsorbed onto L-tyrosine. The allergen extracts are characterised and standardised through immunological and biochemical methods to ensure batch-to-batch consistent allergen content and allergenic potency. Major allergens are measured in selected extracts. Standardisation is reflected by the assignment of Standardised Units (SU).
Shardlow et al. (PTO-892; Reference W) is being used as an evidentiary reference to show that microcrystalline tyrosine is composed of highly crystalline needles, the majority of which exceeded 10 mm in length under physiological conditions (median size – 20.8 mm). While the substantial length of crystals presented a significant barrier to cellular recognition and uptake, isolated incidences of perpendicular recognition were observed owing to the smaller comparative width of crystallites (median size – 2.8 mm). As such, claims 4 and 15 are inherent in the teachings of POLLINEX Grasses + Rye technical leaflet.
The claimed invention differs from the prior art in the recitation of the first dose (i) a first subcutaneous injection of a composition comprising one or more pollen antigens in a dose of 300 to 1500 SU; (ii) a second subcutaneous injection of a composition comprising one or more pollen antigens in a dose of 2000 to 4000 SU, wherein the second subcutaneous injection is administered 6 to 9 days after the first subcutaneous injection; (iii) a third subcutaneous injection of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU, wherein the third subcutaneous injection is administered 6 to 9 days after the second subcutaneous injection; (iv) a fourth subcutaneous injection of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU, wherein the fourth subcutaneous injection is administered 21 to 35 days after the third subcutaneous injection; (v) a fifth subcutaneous injection of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU, wherein the fifth subcutaneous injection is administered 21 to 35 days after the fourth subcutaneous injection; and (vi) a sixth subcutaneous injection of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU, wherein the sixth subcutaneous injection is administered 21 to 35 days after the fifth subcutaneous injection wherein the compositions comprise one or more antigens comprising MPL, 3-DMPL or a derivative or salt thereof of claim 1; wherein the final subcutaneous injection is administered within 2 months prior to the predicted start of the pollen season of claim 2; and a kit comprises:(i) a first vial comprising 0.5 to 2.0 mL of a composition comprising one or more pollen antigens in a dose of 300 to 1500 SU/mL;(ii) a second vial comprising 0.5 to 2.0 mL of a composition comprising one or more pollen antigens in a dose of 2000 to 4000 SU/mL; (iii) a third vial comprising 0.5 to 2.0 mL of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU/mL;(iv) a fourth vial comprising 0.5 to 2.0 mL of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU/mL; (v) a fifth vial comprising 0.5 to 2.0 mL of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU/mL; and (vi) a sixth vial comprising 0.5 to 2.0 mL of a composition comprising one or more pollen antigens in a dose of 5000 to 8000 SU/mL; wherein each of the compositions comprising one or more pollen antigens comprises purified allergen extracts of pollen, wherein the allergens are modified by treatment with glutaraldehyde and adsorbed onto L-tyrosine, and wherein each of the compositions comprising one or more antigens comprises an adjuvant selected from MPL, 3-DMPL or a derivative or salt thereof of claim 13; wherein the MPL, 3-DMPL or a derivative or salt thereof has a mean particle size of 200 nm or less of claim 17; wherein each composition comprising one or more pollen antigens comprises MPL, 3-DMPL or a derivative or salt thereof in an amount of 25 to 100 pg/mL of claim 18 and wherein each composition comprising one or more pollen antigens comprises L-tyrosine in an amount of 2% w/v and MPL, 3-DMPL or a derivative or salt thereof in an amount of 50 pg/mL of claim 19.
Zielen et al. teaches that earlier dose response studies using CPT with Pollinex Quattro Birch (PQ Birch), differing only in the allergoid from PQ Grass, demonstrated a 50% greater reduction of the total symptom score (TSS) after a 5.5-fold increase in the cumulative dose (from 5100 SU to 27300 SU) without compromising safety. The reference teaches a PQ Grass dose response study, three higher injection strengths of 2700 SU, 6000 SU and 8000 SU (per 1.0 mL), were developed. These were used to administer cumulative allergoid doses of 5100 SU, 14400 SU, 27600 SU or 35600 with the same short course of six weekly injections.
Zielen et al. teaches that the study sponsor provided all study medication. PQ Grass or placebo were administered as 6 1.0 mL subcutaneous injections at 7-day intervals over a period of approximately 31–41 days at concentrations of 0 (placebo), 300, 800, 900, 2000, 2700, 6000 and 8000 SU per 1.0 mL to deliver cumulative doses of 0, 5100, 14400, 27600, and 35600 SU. The treatment arm (5100 SU) consisting of 4 active injections started with 2 placebo injections for a total of 6 weekly (7 days, 1) 1.0 mL injections, maintaining the blind for treatment arms with 6 active injections and the overall study. Active injections contained 50 mg/1.0 mL of MPL adjuvant, 2% (w/v) L-tyrosine (MCT); placebo contained no MPL adjuvant. Treatment was to be completed at least 3 weeks before the predetermined start of the local grass pollen season. The start of the grass pollen season was estimated for each of the pollen stations participating in the study (with a pollen station assigned to one or more neighboring clinical sites). For each of these pollen stations, the beginning of the grass pollen season was predicted using historical pollen data. The start date was estimated as the first date reaching at least 1% of the cumulative pollen load in the previous grass pollen season(s).
Heath et al teaches MCT® is a biodegradable depot adjuvant developed primarily for use in short-course subcutaneous allergy immunotherapy (AIT), in combination with native allergens or modified allergens (allergoids) with or without Monophosphoryl Lipid A® (MPL®, a Toll-like receptor 4 agonist) (48). Allergoid MCT®- MPL® formulations are referred to as Pollinex Quattro®. Clinical evidence for the use of allergoid-MCT®-MPL® adjuvant systems in allergy immunotherapy is well documented (55, 56). Combining an allergoid with an adjuvant system pays tribute to the short-course posology of the vaccine, which is administered in four to six injections within a year preseasonally, as opposed to longer-treatment courses (>30 injections) that are commonly applied in AIT and which are typically combined with alum depots (57). (In particular, page 4, whole document).
Heath et al teaches the most recent phase II studies (including the optimal dose levels planned for Phase III) have recently been published for a six-injection presentation of Pollinex Quattro (PQ) Birch and PQ Grass (49, 55). These products are subject to further clinical development, and a phase III trial for both PQ Birch and PQ Grass are currently planned. (In particular, page 4, whole document).
Heath et al teaches that Pollinex Quattro is listed in the current European Academy of Allergy and Clinical Immunology (EAACI) AIT guidelines with grade IA recommendation (56). The PQ products employing the MCT® and MPL® adjuvant system are designed to desensitise allergic individuals by modulating the inherent Th1/Th2 imbalance of atopic disease. The mechanism involved in MCT® -MPL® adjuvancy has not been fully elucidated, but the synergistic attenuation of IgG may prolong protective immunity, which is a further benefited by combining the two adjuvants. (In particular, page 4, whole document).
Heath et al teaches in total, 26 Phase I-III clinical trials have been conducted using various allergoids, with different formulations and dosing posologies, including 4695 patients in total (Table 2). The combination of MCT® and MPL® has been shown to be safe and well tolerated in these Phase I-III studies and based on post-marketing data, i.e., >150,000 individuals have received PQ treatment (2004–2019) and an estimated >450,000 treatment courses have been dispensed (Data on file, Allergy Therapeutics plc). Moreover, the safety of MPL® has been demonstrated in several products using MPL® as an adjuvant (60). (In particular, page 4, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have altered the dosages taught in the Pollinex Grasses and Rye technical leaflet reference in view of the teachings in Zielen et al. and Heath et al. Heath et al teaches that 26 Phase I-III clinical trials have been conducted using various allergoids, with different formulations and dosing posologies, including 4695 patients in total and that studies have been done to determine optimal dose levels for a six-injection presentation. Zielen et al. teaches administering 6 1.0 mL subcutaneous injections at concentrations of 300, 800, 900, 2000, 2700, 6000 and 8000 SU per 1.0 mL to deliver cumulative doses of 0, 5100, 14400, 27600, and 35600 SU. Zielen et al. also teaches that treatment was to be completed at least 3 weeks before the predetermined start of the local grass pollen season wherein the start of the grass pollen season was estimated by determining the beginning of the grass pollen season using historical pollen data. The start date was estimated as the first date reaching at least 1% of the cumulative pollen load in the previous grass pollen season(s). Given that Heath et al. teaches determining optimal posology including timing, dosage levels and frequency, it would have been obvious to one of ordinary skill in the art to have altered the dosage, timing and frequency of administering Pollinex Grasses and Rye. Zielen et al. specifically teaches individual doses of 300, 800, 900, 2000, 2700, 6000 and 8000 SU, all of which would be encompassed by the instant claim recitations of claims 1 and 13 and claims dependent thereupon. In addition, Zielen et al. teaches delivering cumulative doses of 27600, and 35600 SU which are both in the range of the claimed cumulative dosages of 22,300-37,500 SU recited in claims 1 and 13. It would have been obvious to one of ordinary skill in the art at the time of invention to have altered the individual and cumulative dosages to determine the optimal individual and cumulative dosages and to have altered them to dosages that are already taught to be used and effective in Zielen et al.
It would also have been obvious to one of ordinary skill in the art to have changed the time between the third and fourth dose of Pollinex Grasses and Rye technical leaflet reference from 14 days to 2-4 weeks. This would have been obvious to change the timing between dosages to determine the optimal timing and because the timing between the fourth and fifth dose in the Pollinex Grasses and Rye technical leaflet reference was 2-4 weeks. As such, it would have been obvious to change the previous dosage frequency to match the subsequent dosage frequency. A timing of 2-4 weeks falls within the recited 21-35 days.
Lastly it would have been obvious to one of ordinary skill in the art to have administered the final subcutaneous injection “within 2 months prior to the predicted start of pollen season” as recited in claim 2. Pollinex Grasses and Rye technical leaflet reference teaches the course should be completed before the onset of the grass pollen season. Zeilen teaches that treatment “was to be completed at least 3 weeks before the predetermined start of the local grass pollen season.” And Heath teaches the doses are administered in four to six injections within a year preseasonally. The teaching of Zeilen of 3 weeks is within 2 months prior to the predicted start of pollen season. Additionally, it would have been obvious in view of the teachings in Heath and Zeilen to have altered the timing of the method to optimize the method to administer the final dose 2 months prior to the start of pollen season. By completing dosing earlier it would have decreased any intraseasonal dosing safety concerns even further than those at 3 weeks.
It would also have been obvious to one of ordinary skill in the art at the time of Applicant's invention was made to determine all operable features of optimal posology-timing, dosage and frequency because optimal posology-timing, dosage and frequency is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art, particularly in view of the specific teaching of such in Heath et al. The determination of the optimal dosage, including timing, frequency and route of treatment are well within the purview of one of ordinary skill in the art at the time the invention was made and lend no patentable import to the claimed invention. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II.
Hopkins et al. (PTO-892; Reference X) is being used as an evidentiary reference. It teaches an in depth analysis of the MPL adjuvant (In particular, page 247-248, whole document). Hopkins et al teaches the concentration and congener composition of the raw material MPL adjuvant aqueous formulation (MPL-AF) as supplied by the manufacturers and the 0.1mg/ml Intermediate bulk dilutions are determined by reverse phase HPLC assay on a Waters Symmetry C18 column, particle size 5 µm, dimensions 4.6 × 150 mm (19). A fluorescence detection system employed an excitation wavelength of 345nm and emission at 515 nm. A gradient elution protocol used mobile phases of: [A] 5 mM tetrabutylammonium phosphate (TBAP), in acetonitrile-water (95:5, v/v), [B] 5mM TBAP in isopropanol-water (95:5, v/v). Elution of the congeners is accomplished by applying a linear gradient of 10% to 80 % [B] over 45 minutes. Since MPL adjuvant is not a good chromophore, spectrophotometric detection sensitivity is improved by derivatization with dansyl hydrazine (a fluorescent tag) prior to analysis. Hopkins et al. teaches The total MPL content and congener composition of the test sample (prior to the addition to the vaccine formulation) is established by comparison of various peak areas on the chromatogram with those from a 20 μg aliquot of derivatised MPL adjuvant standard. The values obtained are compared with those given on the certificate of analysis from the manufacturer (raw material) or the in-house specification (0.1 mg/ml intermediate). (In particular, page 247-248, whole document) The reference teaches the HPLC profile of MPL in Figure 5 and assay results in Table V. Absent evidence to the contrary, the recitation of the MPL having a mean particle size of 200 nm or less is inherent as evidenced by the results from the Pollinex Quattro composition in Hopkins. As such, the recitations of claims 7 and 17 are inherent in the combined teachings of the references.
From the combined teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference, especially in the absence of evidence to the contrary.
Applicant’s arguments as they relate to the previous rejection have been fully considered, but are not found persuasive.
Applicant argues that the references would lead one of ordinary skill in the art to a shorter course rather than extending treatment.
It is the Examiner’s position that there is nothing in the art of allergen immunotherapy which would lead one of ordinary skill in the art to preferentially choose a shorter course over a longer course without specific data to show that such a course would provide unexpectedly better results. Allergen immunotherapy methods are known in the art to be administered over the course of years. So, any argument that one of ordinary skill in the art would assume that a shorter course would be better without specific data supporting that idea is unpersuasive. One of ordinary skill in the art would assume a longer course which reaches higher dosages would be more effective for desensitization.
9. No claim is allowed.
10. 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 extension fee 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 date of this final action.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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July 14, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
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