DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
2. As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
3. Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-2, 5-9, and 23-24, drawn to a method of making a dry thermostable sterilized pharmaceutical.
Group II, claims 34-36, 39-40, 43, 57, and 59, drawn to another method of making a dry thermostable sterilized pharmaceutical.
4. The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of:
a method of making a dry thermostable sterilized pharmaceutical, comprising; comprising: stabilizing the biopharmaceutical at ambient temperatures using drying; and
subsequently exposing the stabilized biopharmaceutical to ultraviolet radiation at ambient temperatures having a dose between and inclusive of 0.2 J/cm2 and 10 J/cm2 to decrease viability of the microorganisms,
this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Bronshtein (US 9744227 B2, cited in Applicant’s IDS filed 08/22/2024), further in view of Kochel et al. (US 20110014233 A1, cited in Applicant’s IDS filed 08/22/2024).
Bronshtein teaches a method of making a dry thermostable sterilized pharmaceutical (abstract), comprising:
stabilizing the biopharmaceutical at ambient temperatures using drying (col.3, lines 64-66); and
subsequently exposing the stabilized biopharmaceutical to ultraviolet radiation at ambient temperatures to decrease viability of the microorganisms (col.3, lines 66-67, where the radiation can be UV radiation, col.8, line 58).
Bronshtein fails to mention the specific dosage of the UV radiation having a dose between and inclusive of 0.2 J/cm2 and 10 J/cm2.
Kochel teaches the UV inactivation of the viral vaccine before administration ([0023] and claim 1), further citing an intensity of 150 uW/cm-2 to 200 mW/cm-2 (claim 13) and an exposure time of 5-10 minutes (claim 12) in order to “sufficiently long to render the virus non-infectious” (claim 1).
Bronshtein and Kochel are both considered to be analogous to the claimed invention because they are in the same field of UV-based inactivation of vaccines.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the intensity and duration of UV exposure to be a conventional intensity value of 5 mW/cm-2 and a conventional exposure time of 10 minutes as taught by Kochel, because doing so would be “sufficiently long to render the virus non-infectious” (Kochel, claim 1) with a reasonable expectation of success, and in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Because Energy (J/cm2) = Intensity (mW/cm-2) x Time (s) / 1000, the selected parameters would yield an energy level of 1.5 J/cm2.
5. During a telephone conversation with Cy Bates on 08/10/2026 a provisional election was made without traverse to prosecute the invention of Group I, claims 1-2, 5-9, and 23-24. Affirmation of this election must be made by applicant in replying to this Office action. Claims 34-36, 39-40, 43, 57, and 59 withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
6. Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species or invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention or species may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected invention or species.
Should applicant traverse on the ground that the inventions have unity of invention (37 CFR 1.475(a)), applicant must provide reasons in support thereof. Applicant may submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. Where such evidence or admission is provided by applicant, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Due to the complex nature of the above set forth election/restriction requirement, a telephone call was not made to the Applicant’s agent to request oral election. See MPEP § 812.01.
7. Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claim Objections
8. Claims 1-2 are objected to because of the following informalities:
In claim 1, line 2, “biopharmaceuticals” should be corrected to “biopharmaceutical”
In claim 2, line 2, the claim recites “dry stabilized” instead of “dry stabilized biopharmaceutical”
In claims 7-8, “the ultraviolet ionizing radiation” should be corrected to claim 1’s “ultraviolet radiation”, or vice versa.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
9. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
10. Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation “psoralens and their derivatives”, and the claim also recites “like 4'-Aminomethyltrioxalen hydrochloride (AMT), 8- Methoxypsoralen (8-MOP), 4, 5', 8-Trimethylpsoralen (TMP), or other molecules that interact with RNA or DNA under the UV irradiation” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The instant claim language will be interpreted as if AMT, 8-MOP, TMP, and other molecules that interact with DNA/RNA under UV radiation are merely exemplary of the remainder of the claim, and therefore not required.
Claim Rejections - 35 USC § 103
11. 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
12. Claims 1-2, 5-9, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Bronshtein (US 9744227 B2), further in view of Kochel et al. (US 20110014233 A1).
Regarding claim 1, Bronshtein teaches a method of making a dry thermostable sterilized pharmaceutical (abstract), comprising:
stabilizing the biopharmaceutical at ambient temperatures using drying (col.3, lines 64-66); and
subsequently exposing the stabilized biopharmaceutical to ultraviolet radiation at ambient temperatures to decrease viability of the microorganisms (col.3, lines 66-67, where the radiation can be UV radiation, col.8, line 58).
Bronshtein fails to mention the specific dosage of the UV radiation having a dose between and inclusive of 0.2 J/cm2 and 10 J/cm2.
Kochel teaches the UV inactivation of the viral vaccine before administration ([0023] and claim 1), further citing an intensity of 150 uW/cm-2 to 200 mW/cm-2 (claim 13) and an exposure time of 5-10 minutes (claim 12) in order to “sufficiently long to render the virus non-infectious” (claim 1).
Bronshtein and Kochel are both considered to be analogous to the claimed invention because they are in the same field of UV-based inactivation of vaccines.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the intensity and duration of UV exposure to be a conventional intensity value of 5 mW/cm-2 and a conventional exposure time of 10 minutes as taught by Kochel, because doing so would be “sufficiently long to render the virus non-infectious” (Kochel, claim 1) with a reasonable expectation of success, and in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Because Energy (J/cm2) = Intensity (mW/cm-2) x Time (s) / 1000, the selected parameters would yield an energy level of 1.5 J/cm2.
Regarding claim 2, modified Bronshtein teaches wherein the dry stabilized biopharmaceutical comprises two or more glass forming protective molecules (“drying technique for preserving sensitive biological material in an amorphous sugar-glass”, col.8, lines 18-20) comprising carbohydrates (“an amorphous solid carbohydrate matrix including one or more carbohydrates”, col.8, lines 24-25).
Regarding claim 5, modified Bronshtein teaches wherein the ultraviolet ionizing radiation dose comprises between and inclusive of 1 J/cm2 and 10 J/cm2 (the selected parameters in claim 1 would yield an energy level of 1.5 J/cm2).
Regarding claim 6, modified Bronshtein teaches wherein the biopharmaceutical comprises blood components (“active biologicals including… protein antigens from blood”, col.4, lines 35-36).
Regarding claim 7, modified Bronshtein teaches ultraviolet ionizing radiation (col.3, lines 66-67, where the radiation can be UV radiation, col.8, line 58), but fails to teach the specific wavelength the vaccine is sterilized at.
Kochel teaches exposing the biopharmaceutical composition to UV wavelengths of 300-400 nm ([0008]) to effectively inactivate pathogens present in the composition, especially when combined with a psoralen ([0008]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the UV wavelength to be 300 nm as taught by Kochel, because doing so would effectively inactivate pathogens present in the composition, especially when combined with a psoralen (Kochel, [0008]) with a reasonable expectation of success, and in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Regarding claim 8, modified Bronshtein teaches ultraviolet ionizing radiation (col.3, lines 66-67, where the radiation can be UV radiation, col.8, line 58), but fails to teach the specific wavelength the vaccine is sterilized at.
Kochel teaches exposing the biopharmaceutical composition to UV wavelengths of 300-400 nm ([0008]) to effectively inactivate pathogens present in the composition, especially when combined with a psoralen ([0008]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the UV wavelength to be 400 nm as taught by Kochel, because doing so would effectively inactivate pathogens present in the composition, especially when combined with a psoralen (Kochel, [0008]) with a reasonable expectation of success, and in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Regarding claim 9, modified Bronshtein teaches the UV irradiation of the dried biopharmaceutical, but fails to teach the adding of psoralens and their derivatives.
Kochel teaches that the exposure of a biopharmaceutical composition having psoralens to UV wavelengths of 300-400 nm causes viral inactivation while keeping the immunogenic surface epitopes intact, serving as a viable vaccine candidate ([0008], see [0029-0033] for embodiments).
Bronshtein and Kochel are both considered to be analogous to the claimed invention because they are in the same field of UV-based inactivation of vaccines.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biopharmaceutical composition of modified Bronshtein by further incorporating psoralens to the composition as taught by Kochel, because doing so would cause viral inactivation while keeping the immunogenic surface epitopes intact, serving as a viable vaccine candidate when exposed to UV radiation (Kochel, [0008]).
Regarding claim 23, modified Bronshtein teaches wherein the dry thermostable sterilized biopharmaceutical comprises an inactivated vaccine (“inactivated biopharmaceuticals for use in vaccines”, abstract).
12. Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Bronshtein (US 9744227 B2), further in view of Kochel et al. (US 20110014233 A1), as applied to claim 23 above, further in view of Ng et al. (US 20170226511 A1).
Regarding claim 24, modified Bronshtein teaches wherein the dry thermostable sterilized biopharmaceutical comprises an inactivated vaccine (“inactivated biopharmaceuticals for use in vaccines”, abstract), specifically citing viral inactivated vaccines such as “Inactivated Poliovirus (IPV), Hepatitis A, inactivated rabies, and injectable seasonal influenza vaccines” (col. 3, lines 30-32).
Modified Bronshtein fails to teach isolating nucleic acid aptamers that bind and are specific to the inactivated vaccines and other biopharmaceuticals in human serum.
Ng teaches the isolation/creation of nucleic acid aptamers (Fig. 14, DNA molecule being aptamer, [0007]) that binds to a specific flavivirus structural protein (biotinylated WNDIII) in human serum (Fig. 20-21) that can be part of a vaccine composition ([0024]) having the screened optimal aptamer(s) to “stimulate active immunity and protect against infection with these or related organisms” ([0024]), further citing that the modified B03 aptamer is highly stable and can withstand the human serum conditions (Fig. 22).
Modified Bronshtein and Ng are both considered to be analogous to the claimed invention because they are in the same field of viral vaccine compositions to illicit an immune response against a viral pathogen.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of producing a dry thermostable sterilized/inactivated vaccine of modified Bronshtein by incorporating the creation and subsequent isolation/screening of the most optimal aptamers that bind to the designated target epitope in human serum as taught by Ng, because doing so would further “stimulate active immunity and protect against infection with these or related organisms” when incorporated with a vaccine composition (Ng, [0024]) with a reasonable expectation of success.
Conclusion
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aham Lee whose telephone number is (703)756-5622. The examiner can normally be reached Monday to Thursday, 10:00 AM - 8:00 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris R. Kessel can be reached on (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Aham Lee/Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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