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 24 July 2026 is acknowledged. Claims 1-3, 10, 12-16, and 18 are currently pending. Of those, claims 1-2, 10, and 18 are amended. There are no new claims and no claims are withdrawn. Claims 4-9, 11, 17, and 19 are cancelled. Claims 1-3, 10, 12-16, and 18 will be examined on the merits herein.
Response to Amendment
Applicants’ arguments filed 24 July 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Final Office Action mailed 20 January 2026 will be referred to as “FOA”.
Objection(s) and Rejection(s) Withdrawn
The objections to claims 1-2, 10, and 18 are withdrawn in view of the amendments to the claims.
The rejections of claim 19 under 35 U.S.C. 112(a) for lacking enablement and written description are moot because the claim is cancelled.
The rejection of claims 1-3, 10, 12-16, and 18 over copending application 18/833,626 is withdrawn in view of Applicants’ arguments (Remarks, pg. 10-11).
Rejection(s) Maintained
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 § 103
Claims 1-3, 10, 12-16, and 18 remain 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”), Alexander and Fisher (1974, J. Infect. Dis.; herein “Alexander”) as evidenced by Church et al. (2006, Clin. Microbiol. Rev.; herein “Church”) and Hanessian et al. (1971, Nature New Biology; herein “Hanessian”), and Hogenesch et al (2018, npj Vaccines; herein “Hogenesch”).
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 at 3,600 Gy (Abstract and pg. 2, para. 1-2). Li also teaches that the P. aeruginosa were irradiated by X-ray radiation at intervals between 500-3600 Gy, including 1000 Gy to evaluate reproductive viability and metabolic activity (pg. 9, para. 2 and Figure 1(A) and (C)). Li teaches that P. aeruginosa is an opportunistic pathogen and is often the primary agent infecting immune compromised patients who suffer from severe burns, but that there are still difficulties in treating P. aeruginosa infection and immunotherapeutics (pg. 1, para. 1). 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 10, 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 New Zealand White rabbits as described in the instant specification (para. 119-120), 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 skin scald complicated with bacterial infection (specification, para. 152-155 and Tables 4 and 5). 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 burn and scald wound, as in claim 1, wherein the burn and scald wound comprises a scald-caused wound that is a I degree scald, superficial II degree scald, deep II degree scald, or III degree scald, as in claim 2, wherein the site of the scald-caused wound is skin and/or mucosa, as in claim 3, a method in which the patient is injected with the P. aeruginosa vaccine three times, as in claim 10, or a P. aeruginosa vaccine further comprising an immunoadjuvant, as in claims 15-16.
Regarding claims 1-3, Alexander teaches a method comprising administering a Pseudomonas aeruginosa vaccine comprising lipopolysaccharide antigens from the most prevalent strains of P. aeruginosa (as evidenced by Hanessian, pg. 209, left col., first para.) to patients with thermal burn injuries (Abstract and pg. S153). Alexander teaches that patients with burn injuries are at risk of P. aeruginosa infection (pg. S152, left col.). Alexander teaches that the vaccine was administered intramuscularly and subcutaneously (pg. S153 and Table 1). Thermal injuries comprise scald injuries which are caused by direct contact with hot liquid to the skin or mucosa and are classified as first-degree, superficial second-degree, deep second-degree, and third degree depending on the depth of the injury (as evidenced by Church, FIG. 1 and pg. 407, right col., para. 1).
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).
Regarding claim 10, 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 15-16, Hogenesch teaches that aluminum adjuvants 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 modify the P. aeruginosa vaccine taught by Li by first using whole-cell P. aeruginosa irradiated at 1,000 Gy and then obtaining membrane vesicles as taught by Zhang from the P. aeruginosa irradiated at 1,000 Gy based on the teachings of Li and adding the resulting membrane vesicles to the whole cell P. aeruginosa vaccine, and administering the resulting vaccine to the subject population described by Alexander, thereby arriving at the invention of claims 1-3 and 12-14. The person of ordinary skill in the art would have been motivated to make the modification because ;P. aeruginosa irradiated at 1,000 Gy still maintain some viability and metabolic activity necessary to obtain membrane vesicles from the irradiated bacteria. Furthermore, one would have been motivated to administer the vaccine to the Alexander’s patient population because the patient population described by Alexander is at risk of P. aeruginosa infection in burn injuries and both the Li and Zhang vaccines protect against infection and reduce bacterial load. 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 Li teaches that method of making the vaccine using irradiated P. aeruginosa and 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., whole-cell irradiated P. aeruginosa vaccine, P. aeruginosa membrane vesicle vaccine, patient population with burn wounds, 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 10, 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 10. 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.
Additionally or alternately, 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.
Response to Arguments
Applicant argues (Remarks, pg. 7-8) that the radiation dosage of 500-3600 Gy taught by Li was used in experiments evaluating the effects of different radiation dosages on bacterial reproductive viability and metabolic activity and that Li did not use 1,000 Gy to prepare it’s vaccine.
Applicant also argues (Remarks, pg. 8-9) that Zhang does not cure the deficiencies of Li because it does not teach membrane vesicles isolated from bacteria inactivated by irradiation at 900-1,000 Gy and that it does not teach a vaccine comprising both inactivated whole-cell Pseudomonas aeruginosa and membrane vesicles isolated from the same irradiated bacteria; therefore, the combination proposed in the FOA would result in a vaccine in which the bacteria has been irradiated at 3,600 Gy and membrane vesicles obtained from nonirradiated bacteria.
This argument has been fully considered but is not persuasive. While Applicant is correct that the irradiated whole-cell P. aeruginosa used by Li in their vaccine was irradiated at 3,600 Gy, Li still teaches whole-cell P. aeruginosa irradiated at 1,000 Gy (pg. 9, para. 2). Therefore, it would have been obvious to use P. aeruginosa irradiated at any of the levels taught by Li, including at 1,000 Gy, to make the vaccine based on Li’s teachings of how to make the whole-cell vaccine and because Li does not specifically teach away from the use of a different radiation dosage. Because it is obvious over the teachings of Li alone to irradiate whole-cell P. aeruginosa at 1,000 Gy, Zhang is not relied upon to teach inactivation of the bacteria at 900-1,000 Gy, but instead to teach the method of obtaining membrane vesicles from P. aeruginosa, which may be applied to the somewhat metabolically active P. aeruginosa irradiated at 1,000 Gy taught by Li. Therefore, it would have been obvious to combine the method of obtaining P. aeruginosa membrane vesicles taught by Zhang with the P. aeruginosa irradiated at 1,000 Gy taught by Li to produce membrane vesicles that may then be combined with the whole-cell irradiated P. aeruginosa in a vaccine composition.
Applicant argues (Remarks, pg. 9-10) that Alexander does not cure the deficiencies of Li and Zhang because Alexander does not teach X-ray irradiation of Pseudomonas aeruginosa, an irradiation dosage of 900-1,000 Gy, or membrane vesicles isolated from irradiated bacteria.
Applicant also argues (Remarks, pg. 10) that the other references cited in the FOA also do not disclose or suggest X-ray irradiation of Pseudomonas aeruginosa, an irradiation dosage of 900-1,000 Gy, or membrane vesicles isolated from irradiated bacteria.
This argument has been fully considered but is not persuasive. In response to applicant's arguments against Alexander individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Alexander is not relied upon to teach the above elements of the claimed invention, but instead to teach the population of patients having burn and scald wound(s) at risk of P. aeruginosa infection in need of vaccination against P. aeruginosa. Furthermore, the additional reference Hogenesch is relied upon to teach the use of aluminum adjuvants in vaccine compositions and not to teach the elements of independent claim 1. As stated in para. 29 above, these references are not needed to cure the deficiency of Li because it would have been obvious to use P. aeruginosa irradiated at 1,000 Gy in the vaccine based on the teachings of Li and to use the method of Zhang to obtain membrane vesicles from the irradiated P. aeruginosa of Li and to add the membrane vesicles to the vaccine composition.
Double Patenting
Claims 1-3, 10, 12-16, and 18-19 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, 12-16, and 18 of copending Application No. 17/637,028 in view of Alexander (1974, J. Infect. Dis.) as evidenced by Church (2006, Clin. Microbiol. Rev.) and Hanessian et al. (1971, Nature New Biology). This is a provisional nonstatutory double patenting rejection.
The following rejection has been amended to reflect the amendments to the ‘028 claims.
Regarding instant claim 1, the ‘028 claims teach a P. aeruginosa vaccine comprising inactivated P. aeruginosa and P. aeruginosa membrane vesicles, wherein the P. aeruginosa is inactivated by irradiation, and the P. aeruginosa membrane vesicles are isolated from the P. aeruginosa inactivated by irradiation at 900-1,000 Gy (‘028 claim 1). The ‘028 claims also teach that the administration site of the P. aeruginosa vaccine is subcutaneous, muscle and/or mucosa (‘028 claim 1).
Regarding instant claim 10, the ‘028 claims teach an immunization procedure of the P. aeruginosa vaccine comprising “injecting the Pseudomonas aeruginosa vaccine into the patient three times: a first injection, a second injection, and a third injection; 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; (2) the second injection is performed one week after the first injection, and the third injection is performed two weeks after the first injection; or (3) the second injection is performed two weeks after the first injection, and the third injection is performed four weeks after the first injection.” (‘028 claim 9).
Regarding instant claim 12, the ‘028 claims teach that the P. aeruginosa vaccine prevents P. aeruginosa infection, and reduces bacterial load in the respiratory disease (‘028 claim 12). Because the ‘028 vaccine is the same composition that was administered to New Zealand White rabbits as described in the instant specification (para. 119-120), 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 skin scald complicated with bacterial infection (specification, para. 152-155 and Tables 4 and 5). 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 instant claims 13-14, the ‘028 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 (‘028 claim 14).
Regarding instant claims 15-16, the ‘028 claims teach the P. aeruginosa vaccine further contains an immunoadjuvant (‘028 claim 15), and that the immunoadjuvant is aluminum hydroxide (‘028 claim 16).
Regarding instant claims 18-19, the ‘028 claims teach that the medicament can also contain any pharmaceutically acceptable carrier and/or adjuvant (‘028 claim 18), and that the carrier is a liposome (‘028 claim 19).
However, the ‘028 claims do not teach a method of treating a patient that has burn and scald wound complicated with P. aeruginosa or a risk of P. aeruginosa infection, as in instant claim 1, a burn and scald wound caused by scald, including I degree scald, superficial II degree scald, deep II degree scald, or III degree scald, as in instant claim 2, and wherein the site of the scald-caused wound is skin and/or mucosa, as in instant claim 3.
Regarding instant claims 1-3, Alexander teaches a method comprising administering a Pseudomonas aeruginosa vaccine comprising lipopolysaccharide antigens from the most prevalent strains of P. aeruginosa (as evidenced by Hanessian, pg. 209, left col., first para.) to patients with thermal burn injuries (Abstract and pg. S153). Alexander teaches that patients with burn injuries are at risk of P. aeruginosa infection (pg. S152, left col.). Alexander teaches that the vaccine was administered intramuscularly and subcutaneously (pg. S153 and Table 1). Thermal injuries comprise scald injuries which are caused by direct contact with hot liquid to the skin or mucosa and are classified as first-degree, superficial second-degree, deep second-degree, and third degree depending on the depth of the injury (as evidenced by Church, FIG. 1 and pg. 407, right 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 administer the P. aeruginosa vaccine taught by the ‘028 claims to the patient population described by Alexander, 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 population described by Alexander is at risk of P. aeruginosa infection in burn injuries and the ‘028 vaccine protect against infection and reduce bacterial load. 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 ‘028 claims is 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., P. aeruginosa vaccine comprising irradiated whole cell P. aeruginosa and membrane vesicles, X-ray irradiation, patients with burn and scald injury, 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.
Response to Arguments
Applicant argues (Remarks, pg. 10) that the claims of copending application ‘028 concern the treatment of a materially different disease and that neither the ‘028 claims nor the cited secondary references provide an adequate reason or reasonable expectation of success for applying the claimed vaccine to a materially different patient population and infection environment.
This argument has been fully considered but is not persuasive. While the ‘028 claims concern a different patient population than in the instant claims, the vaccine composition and method of administering it to a patient taught by the ‘028 claims is identical to that of the instant claims. Because the ‘028 vaccine is the same composition that was administered to New Zealand White rabbits as described in the instant specification (para. 119-120), 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 skin scald complicated with bacterial infection (specification, para. 152-155 and Tables 4 and 5). The ability to treat the respiratory diseases taught by the ‘028 claims does not preclude this fact. 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.
Conclusion
No claim is allowed.
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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