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 .
Response to Amendment
Applicant’s amendment filed on 02/05/26 has been entered. Claims 3-6, 9 and 10 have been canceled. Claims 1-5, and 8-13 remain pending are examined herein. Applicant’s remarks/amendments have overcome each and every objection and rejection under 112(b) set forth in the Office Action mailed on 08/13/25.
Status of Rejections and Objections
The rejection of claims 1-5 and 8-10 under 103 are maintained.
The 112 rejections from the previous OA are withdrawn in light of Applicant’s amendment.
The rejections of claims 6 and 7 are obviated by Applicant’s cancellation of the claims.
New grounds of rejection for claims 11-13 under 35 U.S.C. 103 are necessitated by the amendments.
Claim Objections
Claim 1 is objected to because of the following informalities: “aga rose” should be “agarose”. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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(s) 1-5 and 8-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rubin (The Rat-Based Neurovirulence Safety Test for the Assessment of Mumps Virus Neurovirulence in Humans: An International Collaborative Study, 2005; cited in IDS filed on 05/04/22) in view of Honmou (EP 1658853 A1; cited in IDS filed on 12/18/23) as cited in previous Office Action and Gage (Whole Animal Perfusion Fixation for Rodents, 2012).
Regarding claims 1 and 11, Rubin discloses a device for evaluating the neurovirulence of mumps virus, which comprises:
a virus inoculation module comprising a micro-syringe with a mumps virus solution, the virus inoculation module being configured to inoculate a virus in the lateral ventricle of a rat (1-day-old rats) with the mumps virus to be evaluated (…inoculated with 100 pfu of virus in a 10-mL volume of MEM by use of a 27-gauge needle.) (Inoculation of rats, pg. 1124), wherein the rat is taken as a sample I on the 22nd-28 days after the virus inoculation, and the rat is 1 to 3 days old (1-day-old rats; On day 25 after inoculation, all rats were euthanized; Inoculation of rats, pg. 1124),
wherein the inoculation amount is 100 PFU, which is approximately 69 CCID50 (1 CCID50 corresponds to 0.69 PFU). In the alternative where 69 CCID50 does not overlap with the claimed “102 CCID50”, it is the Examiner’s position that the disclosed values are close enough that one of ordinary skill in the art before the effective filing date of the invention would have expected the same properties. Case law holds that a prima facie case of obviousness exists where 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 the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
a processing module configured to take a rat brain from the sample I and fixing it, and to subject the rat brain to a processing procedure to obtain rat brain slices, the processing module being configured to perform vibration slicing on a fixed rat brain, wherein the processing module comprising:
a fixing element for fixing the rat brain sample, wherein the fixing element comprises a fixing solution selected from the group consisting of paraformaldehyde, acetone, ethanol, and a combination thereof (The resulting 3–5-mm–thick sections of brain tissue from each rat were placed in a cassette, were dehydrated by use of a graded series of ethanol baths (70%, 85%, 95%, 100%, 100%, and 100%) in which they were placed for 1 h in each bath; Brain processing, pg. 1124);
embedding (Dehydrated tissues were then immersed in paraffin at 60C for 2 h) and slicing elements (…and were then mounted on a microtome…) (Brain processing, pg. 1124);
an imaging module comprising a scanner, the image module being configured to scan and image the rat brain slices (At the FDA, H-E–stained slides were placed on a scanner; Neurovirulence assessment, pg. 1125); and
an analysis module comprising a software, the analysis module being configured to count the cross-sectional area S1 of the cavity formed by hydrocephalus in the longitudinal sectional of the rat brain and the total cross-sectional area S0 of the rat brain without the cerebellum in the imaging obtained by the imaging module (the scanned image was transferred to a computer. Image Pro Plus image analysis software (Media Cybernetics) was used to measure (in pixel units) the cross-sectional area of the entire brain (excluding the cerebellum) and the cross-sectional area of the lateral ventricle) and calculating the neurovirulence index of the rat by Formula I (As demonstrated in figure 1, the neurovirulence score (hydrocephalus severity) for each brain section is the quotient of the cross-sectional area of the entire brain (excluding the cerebellum) and the cross-sectional area of the lateral ventricle, expressed as a percentage.) (Neurovirulence assessment; pg. 1125),
wherein statistical longitudinal section of the rat brain includes an area of 1 to 2.5 mm on the left side of the sagittal suture of the rat’s left brain (p. 1124-1125, Brain Processing; Fig. 1 and 3).
The limitation of “the rat is taken as sample i on the 22nd to 28th days after virus inoculation” is recitation of intended use. Manner of operating an apparatus does not differentiate apparatus claim from the prior art. A claim containing a “recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus” if the prior art apparatus teaches all the structural limitations of the claim (MPEP 2114, II). A recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Furthermore, Rubin discloses the rat is taken as sample on the 25th day after virus inoculation (On day 25 after inoculation, all rats were euthanized; Inoculation of rats, pg. 1124).
The limitation regarding the positioning of virus inoculation in lines 8-10 are also intended use recitation for similar reason as discussed above. Furthermore, Rubin discloses the position of the virus inoculation is between the bregrna and the lambda in the rat brain, 2 mm on the left side of the sagittal suture (The inoculation site was in the left parietal area of the skull, ∼2 mm left of midline and midway between the bregma and lambda., pg. 1124).
Rubin alone does not disclose the processing module comprises an anesthesia element comprising an anesthetic and anesthetic syringe and perfusion element. Instead, Rubin discloses the rats were knocked out/euthanized by carbon dioxide asphyxiation. In an analogous art, Honmou discloses a method of extraction of test sample from Wistar rats (para. [0195]) comprising: anesthetic and anesthetic syringe (The animals were anaesthetized with intraperitoneal (IP) injection of ketamine (2.7 to 3 mg/100-g) and xylazine (0.36 to 0.4 mg/100-g); para. [0197]; Note based on the procedure of injecting ketamine to the rat, a person of skilled in the art would recognize an anesthetic syringe as potential tool for injecting the ketamine), and a perfusion solution for the heart after rats were anaesthetized (the heart was perfused first with PBS, then with a fixative solution containing 4% paraformaldehyde in 0.14 M Sorensen's phosphate buffer (pH 7.4). para. [0123]).
Gage discloses the purpose of including a perfusion step is for better preservation of brain (Abstract).
It would have been prima facie obvious to substitute the carbon dioxide asphyxiation of Rubin’s method with the injection anesthetic such as ketamine as an alternative of knocking the rats out before extraction of biological samples (First, the brains of the deeply anaesthetized rats were removed, fixed by leaving to stand in a phosphate buffer to which 0.5% glutaraldehyde had been added. Para. [0107]), it would also have been obvious to one of ordinary skill in the art before the effective filing date to incorporate a perfusion step the method/device of Rubin by using the perfusion solution of Honmou to in order to better preserve rat brain sample (Gage, Abstract).
Rubin alone also does not disclose the microtome used is configured to perform vibration slicing. Honmou discloses vibratome (interpreted as vibrating slicing machine) were used to slice rat brain samples (para. [0107] and [0113]). It would have been prima facie obvious to substitute the microtome of Rubin’s method with a vibratome to yield to predictable result of sectioning rat brain tissues (Honmou, Para. [0107] and [0113]).
Regarding claim 2, Modified Rubin discloses the claimed method as discussed above in claim 1. Rubin discloses the rat is a Lewis rat (Inoculation of rats, pg. 1124).
Regarding claim 3, Modified Rubin discloses the claimed method as discussed above in claim 1. Rubin discloses the rat is 1 day old (Pregnant Lewis rats were purchased from either Harlan Sprague Dawley (FDA) or Bicester (NIBSC). Two to 3 litters of 1-day-old rats were inoculated; Inoculation of rats, pg. 1124).
Regarding claim 4, Modified Rubin discloses the claimed invention as discussed above in claim 1. The claim limitation Is interpreted as recitation of intended use. Manner of operating an apparatus does not differentiate apparatus claim from the prior art. A claim containing a “recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus” if the prior art apparatus teaches all the structural limitations of the claim (MPEP 2114, II). A recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Furthermore, Rubin discloses the position of the virus inoculation is between the bregrna and the lambda in the rat brain, 2 mm on the left side of the sagittal suture (The inoculation site was in the left parietal area of the skull, ∼2 mm left of midline and midway between the bregma and lambda., pg. 1124).
Regarding claim 5, Modified Rubin discloses the claimed invention as discussed above in claim 1. Rubin discloses the inoculation amount is 100 PFU, which is approximately 69 CCID50 (1 CCID50 corresponds to 0.69 PFU). In the alternative where 69 CCID50 does not overlap with the claimed “102 CCID50”, it is the Examiner’s position that the disclosed values are close enough that one of ordinary skill in the art before the effective filing date of the invention would have expected the same properties. Case law holds that a prima facie case of obviousness exists where 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 the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
Regarding claim 8, Modified Rubin discloses the claimed invention as discussed above in claim 1. The claim limitation Is interpreted as recitation of intended use. Manner of operating an apparatus does not differentiate apparatus claim from the prior art. A claim containing a “recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus” if the prior art apparatus teaches all the structural limitations of the claim (MPEP 2114, II). A recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Furthermore, Rubin discloses the anesthetic is injected by intraperitoneal injection (The animals were anaesthetized with intraperitoneal (IP) injection of ketamine; para. [0197]).
Regarding claim 9, Modified Rubin discloses the claimed invention as discussed above in claim 1. Honmou, after incorporation with method of Rubin, discloses paraformaldehyde were used in combination with the perfusion solution (the heart was perfused first with PBS, then with a fixative solution containing 4% paraformaldehyde in 0.14 M Sorensen's phosphate buffer (pH 7.4). para. [0123]).
Regarding claim 10, Modified Rubin discloses the claimed invention as discussed above in claim 1. Rubin discloses the statistical longitudinal section of the rat brain includes an area of 1.8 to 2.2 mm on the left side of the sagittal suture of the rat’s left brain (p. 1124-1125, Brain Processing; Fig. 1 and 3).
Regarding claim 12, Modified Rubin discloses the claimed invention as discussed above in claim 1. Honmou, after incorporation with Rubin, only discloses the thickness of the rat brain slice is 100 microns (para. [0217]) and does not explicitly disclose the operating parameter. As the thicknesses of the slice are variables that can be modified, among others, by adjusting the blade speed and amplitude/frequency of a vibratome, the precise blade speed and amplitude would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed blade speed and amplitude cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the blade speed and amplitude of the vibratome in Honmou to obtain the desired thickness (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223). “[W]here 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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). “[W]here 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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding claim 13, Modified Rubin discloses the claimed invention as discussed above in claim 1. The claim limitation Is interpreted as recitation of intended use as fixing time is directed to device operation. Manner of operating an apparatus does not differentiate apparatus claim from the prior art. A claim containing a “recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus” if the prior art apparatus teaches all the structural limitations of the claim (MPEP 2114, II). A recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Furthermore, Honmou discloses the fixing time is at least 12 hours (overnight; para. [0254]).
Response to Arguments
Applicant's arguments filed 02/05/26 have been fully considered but they are not persuasive.
In response to applicant's argument that the combination of the prior arts failed to disclose certain features (i.e. to replace traditional paraffin section-HE staining so that direct analysis can be performed without staining, pages 7-8; the position of virus inoculation, page 8-9 of the remark), a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
With respect to the new limitation “to replace traditional paraffin…” of claim 1, the claim attempt to define the subject matter in terms of the result to be achieved, but in so doing merely state the underlying problem, without indicating the technical features necessary for achieving this result. The claim does not disclose any structural distinction of the device in order to achieve the results as the Rubin in view of Honmou has taught each and every structural feature of the claim.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICKEY HUANG whose telephone number is (571)272-7690. The examiner can normally be reached M-F 9:30-5:30 PM ET.
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 Kessel can be reached at 5712707698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/M.H./ Examiner, Art Unit 1758
/MARIS R KESSEL/ Supervisory Patent Examiner, Art Unit 1758