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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Nov. 24, 2026. Claims 1, 3-4 and 6-8 are pending and are currently examined.
Claim Rejections - 35 USC § 112 (Written Description)
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.
(Previous rejection- withdrawn) Claims 1-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is withdrawn in view of the amendment filed on Nov. 24, 2025.
(New Rejection-necessitated by amendment) Claims 1, 3-4 and 6-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The amended base claim 1 is directed to a purification method for removing a contaminant from a composition containing a virus particle and the contaminant. The newly added limitations are as follows:
the first adsorbent comprising fluoroapatite,
the first elution step comprising pH gradient elution that comprises a step of changing a
pH value of a solution supplied to the first adsorbent from a first pH value to a second pH value,
the first pH value is acidic,
the second pH value is neutral or alkaline,
the second adsorbent comprising hydroxyapatite,
the second elution step comprising salt concentration gradient elution that comprises
increasing salt concentration.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings. See MPEP 2163. I.
In Regents of the University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997), the Court decided that adequate written description of genetic material "requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention." Id. 43 USPQ2d at 1404 (quoting Fiefs, 984 F.2d at 1171, 25 USPQ2d at 1606). In AbbVie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (Court of Appeals, Federal Circuit 2014), the Court ruled that “[W]ith the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim' s functional boundaries.”).”
The instant specification discloses that they report on the design and experimental validation of a sequential liquid chromatographic procedure using ceramic fluoroapatite (CFAp) and CHAp for purification of the Sabin type 2 strain of poliovirus (See e.g., [0081]), which indicates that the purified virus is a specific virus, Sabin type 2 strain of poliovirus. Also, the Examples disclose a specific pH value for Sabin type 2 virus elution like using gradient from pH 5 to pH 8.2 for CFAp step elution and pH7.2 for CHAp elution (See eg., [0136] to [0155]) and discloses that at pH 6.4, the Sabin type 2 virus fraction still contained protein contaminants (FIG. 6A), whereas the dengue virus fraction appeared to have been separated from the protein fraction (FIG. 7 A) (See [0101]), which indicate the pH value needs to be adjusted base on the virus types. Furthermore, the instant specification discloses the effect of a specific NaCl concentration like 1 and 1.5 M to separate the dsDNA for Sabin type 2 virus purification (See [0120]), which indicates that the NaCI also needs to be adjusted for different virus types, and the salt concentration gradient such as NaPB for CFAp is from 10 mM to 300 mM (See [0107] to [0110]) and for CHAp is from 10 mM to 600 mM (See [0126] to [0129]).
However, the base claim 1 claims a purification method for purify a generic virus using a generic pH gradient elution and salt gradient concentration. There is no evidence to support or demonstrate that the fluoroapatite-containing adsorbent and hydroxyapatite-containing adsorbent can purify any types of viruses through any pH gradient elution, and salt concentration gradient elution as claimed in the instant application.
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117).
As discussed above, the skilled artisan cannot envision the detailed components of the claims. Therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
Accordingly, the specification does not provide sufficient written description to support for the invention as claimed in claims 1, 3-4 and 6-8.
Claim Rejections - 35 USC § 103
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.
(Previous rejection- withdrawn) Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over O’Riordan et al. (US 2010/0279385 A1, published date: Nov. 4, 2010) as evidenced by Ogawa et al. (Bulletin-1986, Bio-Rad-1996) and in view of Bio-Rad-CFT-2024/Bio-Rad-CFT-2024-medium (2004 Bio-Rad Laboratories, Inc., Bulletin 3111) and Kurosawa et al. (Tech Note. Bio-Rad Laboratory, Inc. 2014, Bulletin 6594) as evidenced by Campbell et al. (J Virol. 2005 May;79(10):6281-90).
This rejection is withdrawn in view of the amendment filed on Nov. 24, 2025.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(New Rejection-necessitated by amendment) Claims 1, 4 and 6-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kurosawa et al. ( PLoS One. 2019 Sep 19;14(9): e0222199).
The amended base claim 1 is directed to a purification method for removing a contaminant from a composition containing a virus particle and the contaminant, the purification method comprising: a preparation step of preparing the composition containing a virus particle and a contaminant; a first adsorption step of adsorbing the virus particle on a first adsorbent composed of a calcium phosphate compound by contacting the composition with the first adsorbent; a first elution step of eluting the virus particle from the first adsorbent to obtain a first eluate; a second adsorption step of adsorbing the virus particle on a second adsorbent composed of a calcium phosphate compound by contacting the first eluate with the second adsorbent; and a second elution step of eluting the virus particle from the second adsorbent to obtain a second eluate;
the first adsorbent comprising fluoroapatite, the first elution step comprising pH gradient elution that comprises a step of changing a
pH value of a solution supplied to the first adsorbent from a first pH value to a second pH value,
the first pH value is acidic, the second pH value is neutral or alkaline,
the second adsorbent comprising hydroxyapatite, the second elution step comprising salt concentration gradient elution that comprises increasing salt concentration.
Claim 8 is directed to a method for producing a virus particle, the method comprising steps of preparing a composition containing a virus particle and a contaminant, and removing the contaminant from the composition by the purification method recited in claim 1.
Kurosawa et al. teaches a sequential two-step chromatographic purification of infectious poliovirus using ceramic fluoroapatite and ceramic hydroxyapatite columns, and discloses that they designed a sequential two-step chromatographic technique for purification of the infectious Sabin type 2 vaccine strain of poliovirus from the cell culture supernatant. In the first step, they removed protein contaminants from the Sabin type 2 virus fraction by pH gradient elution on a ceramic fluoroapatite column. In the second step, they removed double-stranded DNA derived from host cells by diluting the virus fraction, directly loading it on a CHAp column, and purifying it using a phosphate gradient with 1 M sodium chloride. This process achieved removal rates of more than 99.95% and 99.99% for proteins and double-stranded DNA, respectively, and was highly reproducible and scalable (See Abstract). The Fig. 1 (page 4 and below) shows the two-step purification using the pH gradient elution and NaPB gradient elution with a high concentration of sodium chloride (NaCl) (See page 4, paragraph 1), which is also teach claim 6 that the first elution step is conducted before the second elution step.
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Regarding claim 4, it requires that the salt concentration gradient elution comprises a step of changing a salt concentration of a solution supplied to the second adsorbent from a first concentration to a second concentration, the first concentration is 10 mM or less, and the second concentration is 100 mM or more. Kurosawa et al. teaches that in Step 1, the cell culture supernatant was loaded directly onto a CFAp column and eluted with a pH gradient. In Step 2, the resulting virus fraction was diluted with 0.9% NaCl, loaded on a CHAp column, and eluted with an NaPB gradient in the presence of a high concentration of NaCl (See page 7, paragraph 1) and the NaPB gradient if from 10 mM to 600 mM (See Fig. 3 and below) which is 100 mM or more as claimed.
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Regarding claim 7, it requires that the virus particle is a poliovirus particle. Kurosawa et al. teaches that they performed the two-step sequential procedure (Steps 1 and 2 described above) to isolate Sabin type 2 virus from the cell culture supernatant. A representative case is shown in Fig 4 and S1 Table. The virus particles were separated by pH gradient elution on a CFAp column (Fig 4A), and the resulting viral fraction “Fr. B” was pooled (See page 6, paragraph 1), where the Sabin type 2 virus particle is a type of Poliovirus particle.
Accordingly, Kurosawa et al. teaches each and every aspect of the claims 1, 4 and 6-8.
Claim Rejections - 35 USC § 103
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.
(New Rejection-necessitated by amendment) Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Kurosawa et al. (PLoS One. 2019 Sep 19;14(9): e0222199) as applied to claims 1, 4 and 6-8 above.
Claim 3 requires that wherein the first pH value is 6.0 or lower, and the second pH value is 7.5 or higher.
Kurosawa et al. teaches that they separated Sabin type 2 virus from the cell culture supernatant on a CFAp column using a linear pH gradient from pH 5.0 to 8.2 in 300 mM NaPB (See e.g., page 5, paragraph 2), which is the first pH that include the range of pH 6.0 or lower as claimed.
For the second pH value, Kurosawa et al. teaches that for Sabin type 2 virus purification, the buffer pH is at (A) 6.4, (B) 7.2, and (C) 8.2 (See page 9, paragraph 4), for influenza virus NYMC X-181 purification, the separation occurred at buffer pH values of (A) 6.5, (B) 6.8, and (C) 7.5. Column, CHAp (40 μm) (See page 10, paragraph 3), which include the required pH range as claimed.
Responses to Applicant’s Remarks
Applicant’s arguments filed on Nov. 24, 2025 has been received and fully considered.
1). Applicant’s amendments regarding the rejections under 35 U.S.C. § 112(a) is considered, and the 112 (a) is withdrawn. However, a new 112(a) rejection is issued in the current action based on applicant’s amendment.
2). As for the US 10,822,591 B2 and US 10,294,460 B2 cited by the applicant for arguing the limitation of the virus to the purification method (See Remarks, page 4), it is not persuasive.
First, these two patents and the instant application are different inventions with different claims, designs and scopes. For example, US 10,294,460 B2 claims a method for purifying a specific poliovirus. Therefore, they cannot be compared for supporting an argument regarding the 112 (a) rejections issued for the instant application.
Second, the instant application claims a specific condition like a generic pH acidic condition for purifying a generic virus. However, not all virus is resistant to an acidic purification condition. Acid-sensitive viruses often cannot be efficiently eluted using highly acidic conditions because the low pH causes the viral capsids to denature, aggregate and leading to inactivation and low recovery. Indeed, the poliovirus Sabin type 2 virus used in the instant specification is an acid-resistant virus. Also, the instant specification discloses that “this new purification method should be appropriate for adenoviruses that are resistant to acidic purification conditions” (See instant specification, [0166]). Therefore, the 112 (a) rejection is issued in the current office action.
3). Applicant’s argument on the rejections under 35 U.S.C. § 103 is considered. The 103 rejection is withdrawn and all the arguments are moot.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am-5:00 pm, EST.
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/RUIXUE WANG/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672