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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4 May 2026 has been entered.
Claim Status
The amended claim set filed on 4 May 2026 is acknowledged. Claims 21-22, 24-25, 27-31, 34-35, 37-41, and 43 are currently pending. Of those, claims 21-22, 27-31, and 37-40 are amended. There are no new claims and no claims are withdrawn. Claims 1-20, 23, 26, 32-33, 36, 42, and 44 are cancelled. Claims 21-22, 24-25, 27-31, 34-35, 37-41, and 43 will be examined on the merits herein.
Response to Amendment
Applicant’s arguments filed 4 May 2026 are acknowledged. For clarity, in this Action, the arguments will be referred to as “Remarks” and the Final Office Action mailed 3 February 2026 will be referred to as “FOA”.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4 May 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objection(s) and Rejection(s) Withdrawn
The objections to and rejections of claims 42 and 44 under 35 U.S.C. 112(b) and 112(d) are moot because the claims are cancelled.
The objection to claim 21 is withdrawn in view of the amendments to the claim.
The rejection of claims 21-22, 28-30, and 38-40 under 35 U.S.C. 112(b) is withdrawn in view of the amendments to the claims.
The rejection of claims 21-22, 24, 27, 29-31, 34, 37, and 39-41 under 35 U.S.C. 103 over Ellingsworth et al. (US 10,357,557 B2) in view of Möhlen et al. (WO 2013/083726 A1; cited in IDS) is withdrawn in view of the amendments to the claims.
The rejection of claims 31, 34-35, 37-40 and 43 under 35 U.S.C. 103 over Lundberg et al. and Möhlen is withdrawn in favor of a new grounds for rejection.
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 21-22, 24-25, 27-30, and 41 remain rejected under 35 U.S.C. 103 as being unpatentable over Lundberg et al. (US 2016/0333056 A1; cited in IDS; here in “Lundberg”) as evidenced by Walpole et al. (2012, BMC Public Health) in view of Möhlen et al. (WO 2013/083726 A1; cited in IDS; herein “Möhlen”).
The following rejection has been amended to reflect the claim amendments.
Regarding claims 21-22 and 27, Lundberg teaches a method comprising administering a pharmaceutical composition to a human (para. 198-199), wherein the pharmaceutical composition may comprise a polypeptide (i.e., a protein antigen), a L-methionine (i.e., a radical quenching compound) as a pharmaceutically acceptable excipient (para. 172-176 and 181), an aluminum adjuvant (para. 182), and polysorbate-20 as a stabilizing compound (i.e., a reactive compound) (para. 184). Lundberg teaches that polypeptide (i.e., protein antigen) of the composition may comprise Lip-S1D1-S2D1, Lip-S4D1-S3hybD1, and Lip-S5D1-S6D1, which have sequences given in SEQ ID NOs: 29, 27, and 33, respectively (para. 178 and 186), and are identical to instant SEQ ID NOs: 1-3, respectively (see alignments in Figures 1-3 below).
Regarding the limitation “a radical quenching compound which is L-methionine, in a molar concentration at least equivalent to the concentration of copper”, Lundberg teaches that the adjuvant used in the composition may be an aluminum adjuvant that makes a solution having less than 350 ppb heavy metal (e.g., copper); however, this concentration is not limited to a single metal, so the concentration of any single metal, including copper, if present, must be lower than 350 ppb (para. 213). Lundberg’s preferred composition (para. 185) comprises 10 mM L-methionine (i.e., 0.01 mol/L), or 1.49 g/L (0.01mol/L *149.21 g/mol (molar mass of L-methionine) = 1.4921 g/L), which is greater than 350 ppb (i.e., 350 µg/L). Thus, in a composition comprising less than 350 ppb heavy metal and 10mM L-methionine taught by Lundberg, the concentration of L-methionine in mol/L is greater than the concentration of any heavy metal, such as copper, in the composition.
Regarding the limitation “at the time of administration”, Lundberg is silent on the “time of administration” and does not teach any modifications or changes to the vaccine formulation prior to administration, i.e., one of ordinary skill in the art would believe that the composition taught by Lundberg is identical to the composition that is administered to the subject in the method taught by Lundberg.
Regarding the administration of OspA heterodimers, Lundberg teaches that the dosage for the vaccine may be between 0.02 µg and 3 µg antigen per kg body weight for adults and between 0.2 µg and 10 µg antigen per kg body weight for children (para. 220). For adults, this would result in a vaccine comprising between about 1.24 µg and 186 µg, based on the average adult weight of 62.0 kg (as evidenced by Walpole et al., Table 3). Lundberg also teaches that the dose may be administered from 1 to 3 times at intervals of 2 to 24 weeks (para. 220).
Regarding claim 25, Lundberg teaches that the concentration of L-methionine may be 10 mM, i.e., 10 mmol/L (para. 185).
Regarding claim 28, Lundberg teaches that the Lip-S1D1-S2D1, Lip-S4D1-S3hybD1, and Lip-S5D1-S6D1 proteins are mixed at a molar ratio (i.e., weight ratio) of preferably 1:1:1 (para. 186).
Regarding claim 41, Lundberg teaches that the aluminum adjuvant may be aluminum hydroxide or aluminum phosphate (para. 182).
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Figure 1: Alignment of instant SEQ ID NO: 1 (Qy) with Lundberg’s SEQ ID NO: 29 (Db), both identified as Lip-S1D1-S2D1.
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Figure 2: Alignment of instant SEQ ID NO: 2 (Qy) with Lundberg’s SEQ ID NO: 27 (Db), both identified as Lip-S4D1-S3hybD1.
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Figure 3: Alignment of instant SEQ ID NO: 3 (Qy) and Lundberg’s SEQ ID NO: 33 (Db), both identified as Lip-S5D1-S6D1.
However, Lundberg does not teach a method in which the OspA heterodimer proteins are administered to a human adult with a protein content of said 3 OspA heterodimers in the range of from 120 to 200 µg per dose; or to a human child with a protein content of said 3 OspA heterodimers in the range of from 60 to 100 µg per dose as in claims 21-22 and 29-30, or copper in the form of an ion, as in claim 24.
Regarding claims 21-22, Möhlen teaches that a protein composition (such as a vaccine comprising a protein antigen) preferably has less than 1 or 0.2 ppb copper, because the presence of copper affects the storage stability of the compositions (pg. 27, lines 19-30). Möhlen also teaches that the presence of heavy metals (including copper) in aluminum-adjuvanted compositions affects the shelf life of compositions containing proteins and that the degradation of proteins increases as time passes; therefore, reduced presence of heavy metals improves protein stability and shelf life (pg. 20, lines 9-27).
Regarding claim 24, Möhlen teaches that copper may be in the form of an ion (pg. 52, line 15, and pg. 70, line 8 – pg. 72, line 12).
Regarding claim 27, Möhlen teaches that the protein composition may further comprise a reactive compound, including a redox active compound, radical building compound, and/or a stabilizing compound (pg. 29, line 24 – pg. 30, line 9).
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 vaccine containing OspA protein antigens, an aluminum adjuvant, and the radical-quenching compound L-methionine taught by Lundberg by using an aluminum adjuvant composition that results in a vaccine comprising less than 1 ppb copper, as taught by Möhlen, and further modify the composition by optimizing the dosage for administration to adults or children based on the parameters taught by Lundberg, thereby arriving at invention of claims 21-22, 24-25, 27-30, and 41. The person of ordinary skill in the art would have been motivated to make the modification because Möhlen teaches that the presence of copper causes protein degradation, which affects the stability of the proteins in the composition and negatively impacts the shelf life and efficacy of the composition. Regarding the dosage of the composition to be administered, one would be motivated to use the parameters set forth by Lundberg to optimize the dosage of the vaccine based on the target population. 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 Möhlen demonstrates that compositions containing less than 1.25 ppb copper show less protein degradation compared to those with higher copper and heavy metal concentrations. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Regarding the limitation, “an aluminum composition with increased antigen bioavailability”, where the claimed and prior art products are identical or substantially identical in structure or composition, … a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Because the combination of Lundberg and Möhlen results in a method comprising administering a composition substantially identical to the aluminum composition of the instant claims (i.e., a composition comprising less than 1.25 ppb copper or L-methionine in a molar concentration at least equivalent to the concentration of copper, an aluminum adjuvant, at least one of the recited reactive compounds, and one of the recited protein antigens), the property of “increased antigen bioavailability” is presumed to be inherent to the combination product. "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
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., aluminum composition comprising less than 1.25 ppb copper, aluminum composition comprising L-methionine, Borrelia OspA heterodimer vaccine and dosages) 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 dosages of the OspA heterodimer proteins of claims 21-22 and 29-30, the range of protein content per dose taught by Lundberg overlaps with the claimed range. Regarding the timing of administration of the three doses recited in claim 30, the range of 1 to 3 doses encompasses the claimed 3 doses, and the administration interval of 2 to 24 weeks overlaps with the claimed administration schedule of a second dose administered 7 days (1 week) after the first dose and the third dose administered 21 days after the first dose (i.e., 2 weeks after the second dose). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985)) (see MPEP 2144.05.01). The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II). Therefore, the claimed dose ranges and administration schedules merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Response to Arguments
Applicant argues (Remarks, pg. 10) that Möhlen does not preclude combining a low-copper composition with an alum adjuvant that may contain excess copper prior to administration and that there is no teaching linking copper content to the process of antigen release from the adjuvant upon administration and subsequent bioavailability.
This argument has been fully considered but is not persuasive. This argument is not persuasive because it merely discusses a hypothetical scenario and fails to point to any errors in the rejection of record. As is set forth in the 103 rejection above, Lundberg teaches administration of a composition which already contains an alum adjuvant with less than 350 ppb of heavy metal (such as copper) and L-methionine in that same composition at a molar concentration greater than that of the 350 ppb of heavy metal. Thus, one of ordinary skill in the art would have been able to follow the teachings of the prior art to arrive at the claimed method with a reasonable expectation of success (see para. 24 above).
Applicant argues (Remarks, pg. 10) that a skilled artisan may add an aluminum-containing adjuvant to a composition after storage and prior to administration without making an effort to keep the copper content below 1.25 ppb in the composition that is actually administered and that one would not have had a reason to ensure that the composition that is administered to the subject still had less than 1.25 ppb copper or at least a molar equivalent concentration of L-methionine without the teachings of the instant specification.
This argument has been fully considered but is not persuasive. This argument is not persuasive because it only discusses a hypothetical scenario and it fails to point to any errors in the rejection of record and does not point to any teachings in the cited references that render the invention nonobvious. Applicant has not pointed to any teachings in the cited references in which an adjuvant is added to the aluminum composition taught by Lundberg after storage of the composition, such that there is more than 1.25 ppb copper or L-methionine at a molar concentration less than that of the copper in the composition. The combination of Lundberg and Möhlen teaches a species of method that falls within the claimed genus of methods; thus, the claimed method is obvious in view of the prior art. See MPEP 2131.02.
Applicant argues (Remarks, pg. 11) that the references of record would not have led the skilled artisan to ensure that a composition satisfied the recited less than 1.25 ppb copper content or at least a molar equivalent L-methionine concentration at the time of administration; thus In re Best and Atlas Powder are inapposite to the claimed methods reciting steps that were neither taught not suggested.
This argument has been fully considered but is not found persuasive. As set forth in the 103 rejection and response to Applicant’s arguments above, the combination of Lundberg and Möhlen teaches all elements and steps of the claimed method. As described in para. 25 above, the composition of Lundberg is substantially identical to the claimed composition; thus, the property of “increased antigen bioavailability” is believed to be inherent. MPEP 2112.01(I) states: “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Applicant has not provided evidence or pointed to any teachings of the cited references that would indicate that the property of “increased antigen bioavailability” is not inherent to the structure of the claimed composition.
Applicant argues (Remarks, pg. 11) that Möhlen does not teach the administration of less than 3 ppb of copper and that because there is no teaching in the cited references that the copper content at the time of administration could adversely affect antigen bioavailability, the copper content of the administered, rather than stored, composition could not be considered a known result-effective variable.
This argument has been fully considered but is not persuasive. Regarding the argument that Möhlen does not teach the administration of less than 3 ppb copper, Möhlen teaches that a protein composition preferably has less than 1 or 0.2 ppb of copper. Thus, one of ordinary skill in the art would have been able to follow the teachings of Möhlen to arrive at a composition comprising less than 1.25 ppb copper and administer said composition to a human with a reasonable expectation of success. Regarding the argument that the cited references do not teach that copper content at the time of administration could affect antigen bioavailability, para. 21 above states that Möhlen teaches that the presence of heavy metals (including copper) in aluminum-adjuvanted compositions affects causes the degradation of proteins over time. One of ordinary skill in the art would understand that protein stability and bioavailability are linked and thus, that the presence of heavy metals (including copper) affects bioavailability. MPEP 2144.05(III)(C) states: “if the prior art does recognize that the variable affects the relevant property or result, then the variable is result-effective.” Additionally, MPEP 2144.05(III)(C) states: “Applicants must articulate why the variable at issue would not have been recognized in the prior art as result-effective.” Applicant has not pointed to any evidence that one of ordinary skill in the art would have recognized that copper concentration affects protein stability but not protein bioavailability before the effective filing date of the claimed invention.
Double Patenting
Response to Arguments
For all double patenting rejections of record, Applicant argues (Remarks, pg. 12-13) that the distinctions between storing a composition at those conditions and ensuring that an administered composition satisfies certain criteria are discussed above with respect to obviousness under 35 U.S.C. 103 and that the amended claims are patentably distinct from the reference claims for at least the same reasons.
This argument has been fully considered but is not persuasive. This argument is not found persuasive for the same reasons as the above arguments and in view of the amended rejections below.
The following rejections have been amended to reflect the amendments to the instant claims.
17/932,226
Claims 21-22, 24-25, 27-28, 29-30, and 41 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-55 and 58 of copending Application No. 17/932,226 ('226) in view of Lundberg (US 2016/0333056 A1; cited in IDS) as evidenced by Walpole et al. (2012, BMC Public Health) and Möhlen (WO 2013/083726 A1; cited in IDS). This is a provisional nonstatutory double patenting rejection.
Regarding instant claims 21-22, 25, and 28, the ‘226 claims teach a method of treating or preventing against a Borrelia infection in a subject, comprising administering to the subject a pharmaceutical composition comprising a mutant fragment of a Borrelia outer surface protein A (OspA) (‘226 claims 49, 53 and 58). The ‘226 claims also teach that the pharmaceutical composition may further comprise L-methionine and aluminum hydroxide (i.e., pharmaceutical composition is an aluminum composition) (‘226 claims 54-55). The ‘226 claims teach that the mutant OspA fragment may comprise Lip-S1D1-S2D1 (SEQ ID NO: 186), which is identical to instant SEQ ID NO: 1 (see alignment below) (‘226 claims 50-52).
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Alignment of instant SEQ ID NO: 1 (Qy) and the ‘226 claims’ SEQ ID NO: 186 (Db), both identified as Lip-S1D1-S2D1.
However, the ‘226 claims do not teach a method comprising administering an aluminum composition comprising less than 1.25 ppb copper to a human, as in instant claims 21-22, copper in the form of an ion, as in instant claim 24, a reactive compound, as in instant claims 21-22, and 27, a composition comprising the OspA heterodimer proteins of SEQ ID NOs: 1-3, as in instant claims 21-22, or the dosages of OspA heterodimer proteins recited in instant claims 21-22 and 29-30. The ‘226 claims are silent on the amount or concentration of L-methionine in the composition.
Regarding instant claims 21-22, and 27, Lundberg teaches a method comprising administering a pharmaceutical composition to a human (para. 198-199), wherein the pharmaceutical composition may comprises a polypeptide (i.e., a protein antigen), a L-methionine (i.e., a radical quenching compound) as a pharmaceutically acceptable excipient (para. 172-176 and 181), an aluminum adjuvant (para. 182), and polysorbate-20 as a stabilizing compound (i.e., a reactive compound) (para. 184). Lundberg teaches that polypeptide (i.e., protein antigen) of the composition may comprise Lip-S1D1-S2D1, Lip-S4D1-S3hybD1, and Lip-S5D1-S6D1, which have sequences given in SEQ ID NOs: 29, 27, and 33, respectively (para. 178 and 186), and are identical to instant SEQ ID NOs: 1-3, respectively (see alignments in Figures 1-3 above).
Regarding the limitation “a radical quenching compound which is L-methionine, in a molar concentration at least equivalent to the concentration of copper”, Lundberg teaches that the adjuvant used in the composition may be an aluminum adjuvant that makes a solution having less than 350 ppb heavy metal (e.g., copper); however, this concentration is not limited to a single metal, so it is assumed that the concentration of a single metal will be much lower than 350 ppb (para. 213). Lundberg’s preferred composition (para. 185) comprises 10 mM L-methionine (i.e., 0.01 mol/L), or 1.49 g/L (0.01mol/L *149.21 g/mol (molar mass of L-methionine) = 1.4921 g/L), which is greater than 350 ppb (i.e., 350 µg/L). Thus, the concentration of L-methionine in mol/L is greater than the concentration of copper in the composition.
Regarding the administration of OspA heterodimers in claims 21-22 and 29-30, Lundberg teaches that the dosage for the vaccine may be between 0.02 µg and 3 µg antigen per kg body weight for adults and between 0.2 µg and 10 µg antigen per kg body weight for children (para. 220). For adults, this would result in a vaccine comprising between about 1.24 µg and 186 µg, based on the average adult weight of 62.0 kg (as evidenced by Walpole et al., Table 3). Lundberg also teaches that the dose may be administered from 1 to 3 times at intervals of 2 to 24 weeks (para. 220).
Regarding instant claim 25, Lundberg teaches that the concentration of L-methionine may be 10 mM, i.e., 10 mmol/L (para. 185).
Regarding instant claim 28, Lundberg teaches that the Lip-S1D1-S2D1, Lip-S4D1-S3hybD1, and Lip-S5D1-S6D1 proteins are mixed at a molar ratio (i.e., weight ratio) of preferably 1:1:1 (para. 186).
Regarding instant claim 41, Lundberg teaches that the aluminum adjuvant may be aluminum hydroxide or aluminum phosphate (para. 182).
Regarding instant claims 21-22, Möhlen teaches that a protein composition (such as a vaccine comprising a protein antigen) preferably has less than 1 or 0.2 ppb copper, because the presence of copper affects the storage stability of the compositions (pg. 27, lines 19-30). Möhlen also teaches that the presence of heavy metals (including copper) in aluminum-adjuvanted compositions affects the shelf life of proteins containing proteins and that the degradation of proteins increases as time passes; therefore, reduced presence of heavy metals improves protein stability and shelf life (pg. 20, lines 9-27).
Regarding instant claim 24, Möhlen teaches that copper may be in the form of an ion (pg. 52, line 15, and pg. 70, line 8 – pg. 72, line 12).
Regarding instant claim 27, Möhlen teaches that the protein composition may further comprise a reactive compound, including a redox active compound, radical building compound, and/or a stabilizing compound (pg. 29, line 24 – pg. 30, line 9).
Therefore, it would have been prima facie obvious, to a person of ordinary skill in the art, to combine the pharmaceutical composition of the ’226 claims with the reactive compound and Lip-S4D1-S3hybD1 and Lip-S5D1-S6D1 heterodimers taught by Lundberg and administer the composition to a human using the dosage parameters taught by Lundberg, thereby arriving at the invention of claims 21-22, 25, 27-28, and 41. The person of ordinary skill in the art would have been motivated to make the modification because all elements taught by the ‘226 claims are taught by Lundberg and one would be motivated to use the parameters set forth by Lundberg to optimize the dosage of the vaccine based on the target population. 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 Lundberg demonstrates that the elements taught by the ‘226 claims may be used in a vaccine and administered to a human. 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., aluminum composition comprising L-methionine and reactive compound, Borrelia OspA heterodimer vaccine and dosages) 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 dosages of the OspA heterodimer proteins of claims 21-22 and 29-30, the range of protein content per dose taught by Lundberg overlaps with the claimed range. Regarding the timing of administration of the three doses recited in claim 30, the range of 1 to 3 doses encompasses the claimed 3 doses, and the administration interval of 2 to 24 weeks overlaps with the claimed administration schedule of a second dose administered 7 days (1 week) after the first dose and the third dose administered 21 days after the first dose (i.e., 2 weeks after the second dose). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985)) (see MPEP 2144.05.01). The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II). Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Additionally or alternately, it would have been prima facie obvious, to a person of ordinary skill in the art, to further modify the composition to comprise less than 1.00 ppb copper as taught by Möhlen, thereby arriving at the invention of claims 21-22, 24-25, 27-28, and 41. The person of ordinary skill in the art would have been motivated to make the modification because Möhlen teaches that the presence of copper causes protein degradation, which affects the stability of the proteins in the composition and negatively impacts the shelf life and efficacy of the composition. 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 Möhlen demonstrates that compositions containing less than 1.25 ppb copper show less protein degradation compared to those with higher copper and heavy metal concentrations. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Regarding the limitation, “an aluminum composition with increased antigen bioavailability”, where the claimed and prior art products are identical or substantially identical in structure or composition, … a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Because the combination of Lundberg and Möhlen results in a method comprising administering a composition substantially identical to the aluminum composition of the instant claims (i.e., a composition comprising less than 1.25 ppb copper or L-methionine in a molar concentration at least equivalent to the concentration of copper, an aluminum adjuvant, at least one of the recited reactive compounds, and one of the recited protein antigens), the property of “increased antigen bioavailability” is presumed to be inherent to the combination product. "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
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., aluminum composition comprising less than 1.25 ppb copper, aluminum composition comprising L-methionine and reactive compound, Borrelia OspA heterodimer vaccine and dosages) 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.
US 11,466,058 B2
Claims 21-22, 24-25, 27-30, and 41 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-10 of U.S. Patent No. 11,466,058 ('058) in view of Lundberg (US 2016/0333056 A1; cited in IDS) as evidenced by Walpole et al. (2012, BMC Public Health) and Möhlen (WO 2013/083726 A1; cited in IDS).
Regarding instant claims 21-22, 25, 28, and 41 the ‘058 claims teach a vaccine comprising Borrelia OspA fragments Lip-S1D1-S2D1 (SEQ ID NO: 186; identical to instant SEQ ID NO: 1) and Lip-S5D1-S6D1 (SEQ ID NO: 190; identical to instant SEQ ID NO: 3), aluminum hydroxide (i.e., an aluminum adjuvant), and L-methionine (‘058 claims 8-10).
However, the ‘058 claims do not teach a method comprising administering the aluminum composition to a human or an aluminum composition comprising less than 1.25 ppb copper, as in instant claims 21-22, copper in the form of an ion, as in instant claim 24, a reactive compound, as in instant claims 21-22 and 27, a vaccine comprising the OspA heterodimer proteins of SEQ ID NOs: 1-3, as in instant claims 21-22 and 28, or the dosages of OspA heterodimer proteins recited in instant claims 21-22, and 29-30. The ‘226 claims are silent on the amount or concentration of L-methionine in the composition.
The teachings of Lundberg with respect to instant claims 21-22, 25, 27-30, and 41 are set forth in the double patenting rejection over 17/932,226 above (para. 45-50).
The teachings of Möhlen with respect to instant claims 21-22 and 24 are set forth in the double patenting rejection over 17/932,226 above (para. 51-53).
Therefore, it would have been prima facie obvious, to a person of ordinary skill in the art, to combine the vaccine of the ’058 claims with the reactive compound and Lip-S4D1-S3hybD1 heterodimer taught by Lundberg and administer the composition to a human using the dosage parameters taught by Lundberg, and further modify the composition to comprise less than 1.00 ppb copper as taught by Möhlen, thereby arriving at the claimed invention.
The motivation and rationale for combining the teachings of the ‘058 claims with Lundberg and Möhlen is the same as that set forth in the double patenting rejection over 17/932,226 above (para. 54-59).
US 10,544,194 B2
Claims 21-22, 24-25, 27-30, and 41 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-9 of U.S. Patent No. 10,544,194 ('194) in view of Lundberg (US 2016/0333056 A1; cited in IDS) as evidenced by Walpole et al. (2012, BMC Public Health) and Möhlen (WO 2013/083726 A1; cited in IDS).
Regarding instant claims 21-22, 25, and 28, the ‘194 claims teach a vaccine comprising Borrelia OspA fragments Lip-S1D1-S2D1 (SEQ ID NO: 186; identical to instant SEQ ID NO: 1) and Lip-S5D1-S6D1 (SEQ ID NO: 190; identical to instant SEQ ID NO: 3), aluminum hydroxide (i.e., the vaccine is an aluminum composition), and L-methionine (‘194 claims 8-9).
However, the ‘194 claims do not teach a method comprising administering the aluminum composition to a human or an aluminum composition comprising less than 1.25 ppb copper, as in instant claims 21-22, copper in the form of an ion, as in instant claim 24, a reactive compound, as in instant claims 27, a vaccine comprising the OspA heterodimer proteins of SEQ ID NOs: 1-3, as in instant claim 28, or the dosages of OspA heterodimer proteins recited in instant claims 21-22 and 29-30. The ‘226 claims are silent on the amount or concentration of L-methionine in the composition.
The teachings of Lundberg with respect to instant claims 21-22, 25, 27-30, and 41 are set forth in the double patenting rejection over 17/932,226 above (para. 45-50).
The teachings of Möhlen with respect to instant claims 21-22 and 24 are set forth in the double patenting rejection over 17/932,226 above (para. 51-53).
Therefore, it would have been prima facie obvious, to a person of ordinary skill in the art, to combine the vaccine of the ’194 claims with the reactive compound and/or Lip-S4D1-S3hybD1 heterodimer taught by Lundberg and further modify the composition to comprise less than 1.00 ppb copper as taught by Möhlen, and administer the composition to a human using the dosage parameters taught by Lundberg, thereby arriving at the claimed invention.
The motivation and rationale for combining the teachings of the ‘058 claims with Lundberg and Möhlen is the same as that set forth in the double patenting rejection over 17/932,226 above (para. 54-59).
New Rejection(s)
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.
Claims 31, 34-35, 37-40, and 43 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 for increasing the bioavailability of a protein in an aluminum-containing composition.
Claim 31 recites, “A method for increasing the bioavailability of a protein in an aluminum-containing vaccine composition, comprising administering the composition to a human….” The broadest reasonable interpretation of this limitation is that the act of administering the aluminum-containing vaccine composition to a human results in the increased bioavailability of the protein in the composition. The instant specification teaches that bioavailability of a protein antigen is reduced when a composition shows reduced desorption of the protein antigen from alum (pg. 2, lines 25-27); thus, the term “increased bioavailability” is interpreted as referring to increased desorption of the protein antigen from the aluminum adjuvant.
Claims 34-35, 37-40, and 43 are rejected for depending upon claim 31.
The nature of the invention; The invention is drawn to a method comprising the step of administering an aluminum-containing vaccine composition to a human. As written, “increasing the bioavailability of a protein” is not a property of the vaccine composition, but the outcome of the administration step, i.e., the bioavailability of the protein is increased after administration of the composition relative to the bioavailability of the protein in the composition prior to administration.
The state of the prior art and the level of predictability in the art: Hansen et al. (2007, Vaccine; cited in IDS; herein “Hansen”) teaches that antigen processing and presentation to T-cells is impaired when the antigen is adsorbed too strongly to the adjuvant and that in vitro elution upon exposure to interstitial fluid or human plasma was inversely related to the adsorptive coefficient, i.e., strong adsorption leads to low desorption (Abstract). Hansen is silent on the differences in desorption of antigen from an adjuvant before and after administration, but indicates that the strength of adsorption observed in vitro is indicative of the ability of the antigen to be processed by the immune system in vivo (section 4). Thus, one of ordinary skill in the art would not have concluded that administration of a given composition would result in a change in the strength of adsorption between an antigen and an adjuvant or change in the ability or the antigen to desorb from the adjuvant (which increased bioavailability).
Based on the prior art, one of ordinary skill in the art would not be able to predict that administration of a vaccine composition to a human would result in an increase of the bioavailability of the antigen bound to an alum adjuvant.
The amount of direction provided by the inventor and the existence of working examples: The instant specification teaches that bioavailability of a protein antigen is reduced when a composition shows reduced desorption of the protein antigen from alum (pg. 2, lines 25-27). The instant specification also teaches that desorption of OspA antigens from an alum adjuvant is higher in compositions in which the alum adjuvant contains low copper concentration (Table 4). However, the specification does not contain any teachings about the desorption of antigens from an alum adjuvant with any copper concentration after administration to a human. The specification does not teach any examples in which the composition is administered to a human or data from any such administration. 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 perform the claimed method without first making a substantial inventive contribution.
In order to perform the claim method in which administering the claimed aluminum-containing vaccine composition to a human results in the increased bioavailability of the protein in the composition, one of ordinary skill in the art would have to determine what process of administration would result in increased desorption of the antigen from the adjuvant when administering the claimed vaccine composition to the subject. To do so without some teaching from the specification or art prior would go beyond what is considered routine in the art because no such method has been taught or suggested in the prior art.
Therefore, claims 31, 34-35, 37-40, and 43 are rejected under 35 U.S.C. 112(a) for failing to meet the enablement requirement.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 29 and 39 are newly rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 29 (which depends upon claim 22) and 39 (which depends upon claim 31) each recite, “the composition is administered to a human adult with a protein content of said 3 heterodimers in the range of from 120 to 200 µg per dose; or to a human child with a protein content of said 3 heterodimers in the range of from 60 to 100 µg per dose.” These claims fail to further limit the subject matter of the claims upon which they depend because claims 22 and 31 recite, “wherein the OspA heterodimer proteins are administered: to a human adult with a protein content of said 3 OspA heterodimers in the range of from 120 to 200 µg per dose; or to a human child with a protein content of said 3 OspA heterodimers in the range of from 60 to 100 µg per dose.” Thus, the scope of claim 29 is identical to that of claim 22, and the scope of claim 39 is identical to that of claim 31.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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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