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 .
Claim Status
The amended claim set filed on 23 May 2026 is acknowledged. Claims 1, 5-6, 9, 12-16, and 18-20 are currently pending. Of those, claims 1, 5-6, 9, 12-16, and 10-20 are amended. There are no new claims, and claim 20 is withdrawn. Claims 2-4, 7-8, 10-11, 17, and 21-22 are cancelled. Claims 1, 5-6, 9, 12-16, and 18-19 will be examined on the merits herein.
Response to Amendment
Applicants’ arguments filed 23 May 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Non-Final Office Action mailed 25 November 2025 will be referred to as “NFOA”.
Objection(s) and Rejection(s) Withdrawn
The objection to the disclosure is withdrawn in view of the amendments to the specification filed 23 May 2026.
The objection to claim 17 and rejections of claims 2 and 17 under 35 U.S.C. 112(b) and 101 are moot because the claims are cancelled.
The objections to claims 1, 9, and 12-15 are withdrawn in view of the amendments to the claims.
The rejections of claims 1, 5-6, 9, 12-16, and 18-19 under 35 U.S.C. 112(b) are withdrawn in view of the amendments to the claims.
The rejection of claims 18-19 under 35 U.S.C. 112(d) is withdrawn in view of the amendments to the claims.
The rejection of claims 1, 5-6, 9, 12-16, and 18-19 under 35 U.S.C. 101 is withdrawn in view of the amendments to the claims.
Claim Objections
Claim 18 is newly objected to because of the following informalities: the phrase “comprises pharmaceutically acceptable carrier” should read “comprises a pharmaceutically acceptable carrier.” Appropriate correction is required.
New Rejection(s)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 19 is newly rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The focus of the enablement inquiry is whether everything within the scope of the claim(s) is/are enabled, at the time of filing, without requiring undue experimentation to make or use the invention. The factors to be considered in determining whether a disclosure would require undue experimentation include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims: With respect to claim breadth, the standard under 35 U.S.C. §112(a) or 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. The claims are drawn to a method of treating a patient, wherein the patient has a respiratory system disease.
Claim 19, which depends upon claim 18, recites, “wherein the carrier is a liposome.” The broadest reasonable interpretation of this limitation is that the P. aeruginosa vaccine as set forth in claim 1 must comprise a liposome that functions as a pharmaceutically acceptable carrier for the P. aeruginosa vaccine (i.e., the irradiated whole-cell P. aeruginosa and/or P. aeruginosa membrane vesicles) and maintain the function of a vaccine (i.e., preventing P. aeruginosa infection).
The state of the prior art and the level of predictability in the art: Correia-Pinto et al. (2013, Int. J. Pharm.; herein “Correia-Pinto”) teaches that vaccines may contain delivery carriers that improve stability, safety, and cost effectiveness (Abstract). Correia-Pinto teaches that some carriers are also capable of inducing an effective immune response (Abstract), and “Vaccine Excipient Summary” (2019) teaches that other excipients (i.e., pharmaceutically acceptable carriers) are included for the specific purpose of preserving or stabilizing (pg. 1, para. 1-2). Common carriers in vaccines administered in the United States include: sodium chloride, formaldehyde, polysorbate, phosphate-buffered saline, sugars, proteins, water, and others (“Vaccine Excipient Summary” Table). Correia-Pinto teaches other antigen carriers and delivery systems that facilitate antigen uptake and overcome mucosal barriers (section 2), including liposomes, which are composed of phospholipid bilayers in the form of small vesicles that incorporate antigens and have been well-characterized in the art (section 3.2). Schwendener (2014, Ther. Adv. Vaccines) teaches that liposomes are primarily used to deliver antigens in subunit vaccines (i.e., comprising proteins, peptides, nucleic acids, carbohydrates, and/or haptens as antigens) because recombinant or synthetic antigens often elicit a week immune response on their own (Abstract and pg. 159, left col.). Schwendener teaches that liposomes may carry antigens in different ways; water-soluble antigens are encapsulated inside the liposome, lipophilic compounds may be embedded within the lipid bilayer, and antigens may be attached to the outer surface of the liposome (Abstract and Figure 2). Because of this flexibility in the type of antigen and how the antigen is delivered by the liposome, liposome composition is highly customizable and variable (Schwendener, pg. 161, right col., para. 2). There is no teaching in the prior art regarding the use of liposomes as a carrier of one or both of whole-cell P. aeruginosa and P. aeruginosa membrane vesicles.
Based on the prior art, one of ordinary skill in the art would not be able to predict that liposomes may be used as a pharmaceutically acceptable carrier for irradiated whole-cell P. aeruginosa and/or P. aeruginosa membrane vesicles in a vaccine that protects against P. aeruginosa infection in patients with burn and scald wounds.
The amount of direction provided by the inventor and the existence of working examples: The embodiments described in the instant specification teach bacterial cells suspended in phosphate buffer solution (para. 69) or normal saline (para. 78), and membrane vesicles suspended in MV buffer (para. 83). The instant specification does not teach any examples of vaccine compositions comprising irradiated whole-cell P. aeruginosa and P. aeruginosa membrane vesicles and liposomes as a pharmaceutically acceptable carrier for one or more antigens. The instant specification also does not provide any guidance for making such a vaccine, such as lipid composition or methodology for encapsulating a P. aeruginosa cell and/or membrane vesicle in a liposome. Therefore, what is enabled by the instant specification and working examples is narrow in comparison to the scope of the claims, and the specification does not provide enough information with which one may overcome the known unpredictability in the art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004)). The instant specification is not enabling for the claimed invention because one cannot follow the guidance presented therein, or within the art at the time of filing, and make or use the claimed composition or perform the claimed method without first making a substantial inventive contribution.
The prior art teaches that pharmaceutically acceptable carriers in whole-cell and subunit vaccines are common and well known in the art. However, neither the instant specification nor the art prior to the effective filing date of the claimed invention teach the use of liposomes as a carrier for irradiated whole-cell P. aeruginosa and/or P. aeruginosa membrane vesicles. Therefore, one of ordinary skill in the art would need to determine the appropriate composition of the lipid bilayer of a liposome and methodology to make and use the liposome capable of use with whole-cell P. aeruginosa and/or P. aeruginosa membrane vesicles, delivering the encapsulated antigen(s), and stimulating an immune response sufficient to protect against P. aeruginosa infection. To do so without some teaching from the prior art or the instant specification would go beyond what is considered “routine” in the art.
Therefore, claim 19 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for failing to meet the enablement requirement.
Claim 19 is newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
MPEP 2163.II.3.a.ii. states (emphasis added):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above)…. A "representative number of species" means that the species which are adequately described are representative of the entire genus.
The broadest reasonable interpretation of claim 19 and the teachings of the art and the instant specification are set forth in the enablement rejection above (see para.16-19).
The teaching of the instant specification is not sufficient to adequately describe a P. aeruginosa vaccine comprising irradiated whole-cell P. aeruginosa and P. aeruginosa membrane vesicles, in which a liposome functions as a pharmaceutically acceptable carrier because the prior art shows that liposome composition and formulation varies depending on the antigen, and the specification does not teach any liposome composition or formulations capable of functioning as a carrier for one or more of the claimed antigens. Furthermore, the embodiments taught by the instant specification are not representative of the vaccine of claim 19 because none of those embodiments comprise a liposome. In other words, there are no species reduced to practice or whose identifying characteristics are described in detail. Therefore, one of ordinary skill in the art would have concluded that the specification has not demonstrated possession of a P. aeruginosa vaccine comprising irradiated whole-cell P. aeruginosa and P. aeruginosa membrane vesicles, in which a liposome functions as a pharmaceutically acceptable carrier for one or more of the recited antigens.
Therefore, claim 19 is rejected because the specification fails to demonstrate possession of the claimed invention.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 5-6, 12-15, and 18 are newly rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (2016, Sci. Rep.; herein “Li”) in view of Zhang et al. (2018, Vaccine; herein “Zhang”) Eller et al. (1998, Chest; herein “Eller”) and Gallego et al. (2014, BMC Pulm. Med.; herein “Gallego”).
Regarding claim 1, Li teaches a method comprising subcutaneously (pg. 2, para. 3) administering a vaccine comprising inactivated Pseudomonas aeruginosa (P. aeruginosa) cells that have been inactivated by X-ray irradiation (Abstract and pg. 2, para. 1-2). Li teaches that the P. aeruginosa were irradiated by X-ray radiation at intervals between 500-3600 Gy, including 1000 Gy (pg. 9, para. 2 and Figure 1(A) and (C)). Li also teaches that inactivated vaccines that cannot replicate are safer vaccine pathogens, but that heat- or formalin-inactivated pathogens are less immunogenic than live, metabolically active vaccines; their irradiated vaccine is beneficial because it cannot replicate, but is metabolically active, thereby activating a robust immune response (pg. 1, para. 3).
Regarding claim 9, Li teaches that the P. aeruginosa vaccine was administered weekly for four weeks (i.e., weeks 0, 1, 2, and 3) in increasing doses of P. aeruginosa CFU in each dose (pg. 10, para. 2-3).
Regarding claim 12, because Li’s vaccine is the same composition that was administered to mice as described in the instant specification (para. 132), it must have the same properties demonstrated by the experiment described in the specification, i.e., the ability to prevent P. aeruginosa infection and reduce bacterial load in the respiratory system (Table 4). When the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978). See also MPEP 2111.02 for a discussion of intended uses in the preamble and MPEP 2112 for a discussion of inherency.
Regarding claims 13-14, Li teaches that the inactivated P. aeruginosa vaccine comprises 1 x 108 or 1 x 109 CFU/injection (i.e., within 1 x 104 – 1 x 1010/injection) (pg. 10, para. 2).
Regarding claim 18, Li teaches that the P. aeruginosa cells were suspended with normal saline (NS), i.e., a pharmaceutically acceptable carrier (pg. 10, para. 1).
However, Li does not teach a P. aeruginosa vaccine comprising P. aeruginosa membrane vesicles isolated from the irradiated P. aeruginosa administered to a patient with a respiratory system disease wherein the respiratory system disease is chronic pulmonary insufficiency complicated with bacterial infection, the chronic pulmonary insufficiency is chronic obstructive pulmonary disease, and the bacterial infection is Pseudomonas aeruginosa infection, as in claim 1, wherein the chronic obstructive pulmonary disease comprises chronic bronchitis and emphysema, as in claim 5, wherein the chronic obstructive pulmonary disease is acute exacerbation of chronic obstructive pulmonary disease, as in claim 6, a method in which the patient is injected with the P. aeruginosa vaccine three times, as in claim 9, or a P. aeruginosa vaccine further comprising an immunoadjuvant, as in claim 15.
Regarding claim 1, Zhang teaches a method of administering to mice P. aeruginosa membrane vesicles (i.e., OMVs, which contain lipopolysaccharides; section 2.2 and pg. 1047, right col., para. 1) intramuscularly (section 2.4) to protect against pneumonia caused by acute P. aeruginosa infection (section 1, para. 4).
Regarding claim 9, Zhang teaches that the vaccine comprising 30 µg OMV per dose was administered three times, comprising a first administration on day 0, a second administration on day 14 (i.e., two weeks after the first administration), and a third injection on day 21 (i.e., three weeks after the first administration) (section 2.4).
Regarding claim 12, Zhang teaches that administration of P. aeruginosa OMVs conferred protection against P. aeruginosa infection (section 3.2) and reduced the bacterial load of P. aeruginosa (section 3.3 and Fig. 3A-B).
Regarding claim 15, Zhang teaches that the P. aeruginosa vaccine comprises aluminum phosphate as an immunoadjuvant (Abstract and section 2.4).
Regarding claim 18, Zhang teaches that the P. aeruginosa vaccine comprises PBS, i.e., pharmaceutically acceptable carrier (section 2.4).
Regarding claims 1 and 5, Eller teaches that P. aeruginosa was isolated from COPD patients with chronic bronchitis (pg. 1543, left col., para. 3, pg. 1544, left col., para. 1, and Table 3).
Regarding claims 1 and 6, Gallego teaches that P. aeruginosa accounts for 5-10% of COPD acute exacerbations and is associated with increased mortality in COPD patient (pg. 2, left col., para. 1).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the P. aeruginosa vaccine taught by Li by first obtaining membrane vesicles, as taught by Zhang, from the irradiated P. aeruginosa taught by Li, and adding the resulting membrane vesicles to Li’s whole cell P. aeruginosa vaccine, and administering the resulting vaccine to the subject populations described by Eller and Gallego, thereby arriving at the invention of claims 1, 5-6, 12-15, and 18. The person of ordinary skill in the art would have been motivated to make the modification because the patient populations described by Eller and Gallego are at higher risk of mortality due to P. aeruginosa infection, and the ;compositions of Li and Zhang protect against infection. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully combining the whole cell vaccine with the membrane vesicles because both the whole cell P. aeruginosa vaccine of Li and the membrane vesicle vaccine of Zhang are protective against P. aeruginosa. Therefore, the combination leads to expected results because each element performs the same function as is does individually. The compositions of Li and Zhang are both made for the purpose of preventing P. aeruginosa infection. From MPEP 2144.06(I): "'It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art.' In re Kerkhoven, 626 F.2d 846,850,205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)...."
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., irradiated whole cell P. aeruginosa, P. aeruginosa membrane vesicles, subjects with COPD complicated with P. aeruginosa infection, immunoadjuvants, etc.) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Regarding the administration schedule of claim 9, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the administration schedules of Li and Zhang to administer a first dose, followed by a second dose two weeks after the first dose and a third dose four weeks after the first dose, thereby arriving at the invention of claim 9. The person of ordinary skill in the art would have been motivated to make the modification in order to optimize the administration schedule of a vaccine comprising both P. aeruginosa whole cells and P. aeruginosa membrane vesicles because the art teaches that the administration schedule may vary (see para. 32 and 39 above). The person of ordinary skill in the art would have has a reasonable expectation of modifying the vaccine administration schedules because the art shows that there is flexibility in the timing and frequency in administering P. aeruginosa vaccines; thus, one would have predicted that the prior art administration schedules could be modified and result in an administration schedule that is at least as successful as those in the prior art. It is noted that the courts have held that optimization through routine experimentation… do not support patentability (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Therefore, the modified administration schedule of claim 10 is merely an obvious variant of that taught by Li and Zhang.
Claim(s) 1, 5-6, 12-16, and 18 are newly rejected under 35 U.S.C. 103 as being unpatentable over Li (2016, Sci. Rep.) in view of Zhang (2018, Vaccine), Eller (1998, Chest) and Gallego (2014, BMC Pulm. Med.) as applied to claims 1, 5-6, 12-15, and 18 above, and further in view of HogenEsch et al. (2018, npj Vaccines; herein “HogenEsch”).
The combination of Li in view of Zhang, Eller, and Gallego is set forth in para. 31-43 above and teaches all limitations of claims 1, 5-6, 12-15, and 18.
However, None of Li, Zhang, Eller, or Gallego teach aluminum hydroxide as the immunoadjuvant, as in claim 16.
Regarding claims 15-16, HogenEsch teaches that aluminum adjuvants, including aluminum hydroxide, have been used in vaccines for many years and that aluminum hydroxide is one of the most commonly used aluminum adjuvants used in vaccines (Abstract and pg. 2, right col., para. 2). HogenEsch also teaches that adsorption of immunostimulatory molecules to aluminum adjuvants can result in more effective and longer lasting immune responses and reduces the risk of systemic side-effects (pg. 7, paragraph bridging columns).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to combine the resulting P. aeruginosa vaccine comprising whole cell irradiated P. aeruginosa and irradiated P. aeruginosa membrane vesicles with aluminum hydroxide as an adjuvant, as taught by HogenEsch, thereby arriving at the invention of claims 15-16. The person of ordinary skill in the art would have been motivated to make the modification because aluminum adjuvants are known in the art to boost the immune response and reduce side effects, and are therefore beneficial in vaccine compositions. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because aluminum adjuvants are common in the art and successfully used in a wide variety of vaccine combinations, and Zhang teaches that their P. aeruginosa OMV vaccine may further comprise an adjuvant. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., P. aeruginosa vaccine comprising irradiated whole-cell P. aeruginosa and P. aeruginosa membrane vesicles, adjuvants, aluminum hydroxide) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5-6, 12-16, and 18-19 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 12-16, and 18-19 of copending Application No. 17/637,057 (‘057) in view of Zhang (2018, Vaccine), Eller (1998, Chest), and Gallego (2014, BMC Pulm. Med.). This is a provisional nonstatutory double patenting rejection.
Regarding instant claim 1, the ‘057 claims teach a method of treating a patient by administering a P. aeruginosa vaccine to the patient, at subcutaneous, muscle and/or mucosa of the patient, wherein the P. aeruginosa vaccine comprises whole-cell inactivated P. aeruginosa and P. aeruginosa membrane vesicles; wherein the inactivated P. aeruginosa is inactivated by irradiation, and the P. aeruginosa membrane vesicles are isolated from the inactivated P. aeruginosa inactivated by irradiation; wherein the ;irradiation is X-ray irradiation at a dosage of 900-1000 Gy (‘057 claim 1).
Regarding instant claim 9, the ‘057 claims teach injecting the P. aeruginosa vaccine into the patient three times; wherein (1) the second injection is performed three days after the first injection, and the third injection is performed seven days after the first injection, or (2) the second injection is performed two weeks after the first injection, and the third injection is performed four weeks after the first injection (‘057 claim 10).
Regarding instant claim 12, the ‘057 claims teach that the method prevents P. aeruginosa infection and reduces bacterial load of P. aeruginosa (‘057 claim 12).
Regarding instant claims 13-14, the ‘057 claims teach the content of the whole-cell P. aeruginosa in the vaccine is 1 x 104/injection, 1 x 105/injection, 1 x 106/injection, 1 x 107/injection, 1 x 108/injection, 1 x 109/injection, and 1 x 1010/injection (‘057 claims 13-14).
Regarding instant claims 15-16, the ‘057 claims teach the P. aeruginosa vaccine further contains an immunoadjuvant (‘057 claim 15), and that the immunoadjuvant is aluminum hydroxide (‘057 claim 16).
Regarding instant claims 18-19, the ‘057 claims teach that the medicament can also contain any pharmaceutically acceptable carrier (‘057 claim 18), and that the carrier is a liposome (‘057 claim 19).
However, the ‘057 claims do not teach a P. aeruginosa vaccine comprising P. aeruginosa membrane vesicles isolated from the irradiated P. aeruginosa administered to a patient with a respiratory system disease wherein the respiratory system disease is chronic pulmonary insufficiency complicated with bacterial infection, the chronic pulmonary insufficiency is chronic obstructive pulmonary disease, and the bacterial infection is Pseudomonas aeruginosa infection, as in claim 1, wherein the chronic obstructive pulmonary disease comprises chronic bronchitis and emphysema, as in claim 5, or wherein the chronic obstructive pulmonary disease is acute exacerbation of chronic obstructive pulmonary disease, as in claim 6.
Regarding instant claim 1, Zhang teaches a method of administering to mice P. aeruginosa membrane vesicles (i.e., OMVs, which contain lipopolysaccharides; section 2.2 and pg. 1047, right col., para. 1) intramuscularly (section 2.4) to protect against pneumonia caused by acute P. aeruginosa infection (section 1, para. 4).
Regarding instant claim 9, Zhang teaches that the vaccine comprising 30 µg OMV per dose was administered three times, comprising a first administration on day 0, a second administration on day 14 (i.e., two weeks after the first administration), and a third injection on day 21 (i.e., three weeks after the first administration) (section 2.4).
Regarding instant claim 12, Zhang teaches that administration of P. aeruginosa OMVs conferred protection against P. aeruginosa infection (section 3.2) and reduced the bacterial load of P. aeruginosa (section 3.3 and Fig. 3A-B).
Regarding instant claim 15, Zhang teaches that the P. aeruginosa vaccine comprises aluminum phosphate as an immunoadjuvant (Abstract and section 2.4).
Regarding instant claim 18, Zhang teaches that the P. aeruginosa vaccine comprises PBS, i.e., pharmaceutically acceptable carrier (section 2.4).
Regarding instant claims 1 and 5, Eller teaches that P. aeruginosa was isolated from COPD patients with chronic bronchitis (pg. 1543, left col., para. 3, pg. 1544, left col., para. 1, and Table 3).
Regarding instant claims 1 and 6, Gallego teaches that P. aeruginosa accounts for 5-10% of COPD acute exacerbations and is associated with increased mortality in COPD patient (pg. 2, left col., para. 1).
Therefore, it would have been prima facie obvious, to a person of ordinary skill in the art, to administer the vaccine taught by the ‘057 claims to the patient populations of Eller and Gallego, thereby arriving at the claimed invention. The person of ordinary skill in the art would have been motivated to make the modification because Zhang teaches that P. aeruginosa membrane vesicle vaccine can prevent infection in subjects with respiratory disease. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because the vaccine of the ‘057 claims is able to prevent infection and reduce bacterial load, so one of ordinary skill in the art would expect the same effect in another patient population. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., irradiated whole cell P. aeruginosa, P. aeruginosa membrane vesicles, patients with COPD, etc.) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 1, 5-6, 12-16, and 18 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 9-10 of copending Application No. 18/833,626 (‘626) in view of Zhang (2018, Vaccine), Eller (1998, Chest), Gallego (2014, BMC Pulm. Med.), and HogenEsch (2018, npj Vaccines). This is a provisional nonstatutory double patenting rejection.
Regarding instant claims 1 and 18, the ‘626 claim 1 teaches a method for producing a vaccine against P. aeruginosa, in which P. aeruginosa cells are inactivated by not less than 1000 Gy (‘626 claim 5) of X-ray irradiation (‘626 claim 1) and resuspended in an isotonic injection (i.e., pharmaceutically acceptable carrier). The ‘626 claims also teach that the vaccine may be a subcutaneous injection, intramuscular injection, or a nasal (i.e., mucosal) administration (‘626 claim 9).
Regarding instant claim 12, the ‘626 claims teach that the vaccine may be used in the preparation of a medicament for preventing P. aeruginosa infection (‘626 claim 10).
However, the ‘626 claims do not teach a P. aeruginosa vaccine comprising P. aeruginosa irradiated P. aeruginosa membrane vesicles administered to a patient with a respiratory system disease wherein the respiratory system disease is chronic pulmonary insufficiency complicated with bacterial infection, the chronic pulmonary insufficiency is chronic obstructive pulmonary disease, and the bacterial infection is Pseudomonas aeruginosa infection, as in claim 1, wherein the chronic obstructive pulmonary disease comprises chronic bronchitis and emphysema, as in claim 5, wherein the chronic obstructive pulmonary disease is acute exacerbation of chronic obstructive pulmonary disease, as in claim 6, a method in which the patient is injected with the P. aeruginosa vaccine three times, as in claim 9, or a P. aeruginosa vaccine further comprising an immunoadjuvant, including aluminum hydroxide, as in instant claims 15-16.
The teachings of Zhang, Eller, and Gallego with respect to instant claims 1, 5-6, 9, 12, 15, and 18 are set forth in para. 65-71 above.
Regarding instant claims 15-16, HogenEsch teaches that aluminum adjuvants, including aluminum hydroxide, have been used in vaccines for many years and that aluminum hydroxide is one of the most commonly used aluminum adjuvants used in vaccines (Abstract and pg. 2, right col., para. 2). HogenEsch also teaches that adsorption of immunostimulatory molecules to aluminum adjuvants can result in more effective and longer lasting immune responses and reduces the risk of systemic side-effects (pg. 7, paragraph bridging columns).
Therefore, it would have been prima facie obvious, to a person of ordinary skill in the art, to modify the vaccine of the ‘626 claims by first obtaining membrane vesicles, as taught by Zhang, from the irradiated P. aeruginosa taught by the ‘057 claims, and adding the resulting membrane vesicles to the ‘057 claims’ whole cell P. aeruginosa vaccine, then adding aluminum hydroxide as an adjuvant to the composition and administering the resulting vaccine to the subject populations described by Eller and Gallego, thereby arriving at the claimed invention. The person of ordinary skill in the art would have been motivated to make the modification because the patient populations described by Eller and Gallego are at higher risk of mortality due to P. aeruginosa infection, and the compositions of the ‘057 claims and Zhang protect against infection. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully combining the whole cell vaccine with the membrane vesicles because both the whole cell P. aeruginosa vaccine of the ‘057 claims and the membrane vesicle vaccine of Zhang are protective against P. aeruginosa. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., irradiated whole cell P. aeruginosa, P. aeruginosa membrane vesicles, subjects with COPD complicated with P. aeruginosa infection, immunoadjuvants, etc.) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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