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 .
Status of the Application
This Office Action is in response to applicant’s arguments filed on 2/10/26. Claims 2-11, 13-16, 18, 23-32, 34-39, 41-66, 73 have been cancelled. Claims 1, 12, 17, 19-22, 33, 40, 67-72, 74 are pending. Claim 72 has been amended. Claims 19-22, 33, 40, 67-71, 74 have been withdrawn. Claims 1, 12, 17, 72 are examined herein.
The claim amendments have rendered the 112 rejection of the last Office Action moot, therefore hereby withdrawn.
Applicant’s arguments with respect to the 103 rejection have been fully considered but found not persuasive, therefore maintained for reasons of record and repeated below for Applicant’s convenience.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 12, 72 are rejected under 35 U.S.C. 103 as being unpatentable over Gagnon et al. (“Chloride extrusion enhancers as novel therapeutics for neurological diseases,” Nature Medicine, 2013, 19, 11, 1524-1531, of record) in view of De Koninck et al (US Patent Application 2010/0330586, of record) and Cramer et al. (“The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury,” Molecular Pain, 2008, 4, 36, of record).
The instant claims are directed to a method for promoting functional recovery after paralysis in a subject having a spinal cord injury resulting in loss of motor and/or sensory function by administering CLP290.
Gagnon et al. teach that enhancing K+-Cl- cotransporter KCC2 activity may be the favored therapeutic strategy to restore inhibition and normal function in pathological conditions involving impaired Cl- transport (abstract). Gagnon et al. teach the identification of KCC2 activators, such as CLP257 (abstract) and its prodrug, CLP290, which possesses improved pharmacokinetics (page 1527, left column, first paragraph). Gagnon et al. provide results that validate KCC2 as a druggable target for CNS diseases (abstract).
However, Gagnon et al. fail to disclose a subject with spinal cord injury.
Cramer et al. teach that in rats that underwent spinal cord injury (SCI), a down-regulation of KCC2 protein was detected. Since expression of KCC2 protein was altered following SCI, it suggests that the loss of KCC2 function plays a role in the development and maintenance of SCI-induced neuropathic pain (abstract). Cramer et al. also teach that SCI and subsequent neuropathic pain can result in devastating motor and sensory deficits (page 2, left column, first paragraph).
De Koninck et al. teach methods of treating pain by the expression of the chloride transporter, KCC2 potassium-chloride cotransporter (abstract). A preferred embodiment of pain is pain associated with spinal cord injury (paragraph 0008 and claim 6). De Koninck et al. teach compounds that are capable of upregulating or increasing KCC2 activity (paragraph 0051 and claims 1-4).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, at the time the claimed invention was made, to have used the KCC2 activator, CLP290, as taught by Gagnon et al., to treat a subject with spinal cord injury, as taught by De Koninck and Cramer et al.
A person of ordinary skill in the art would have been motivated to treat a subject with spinal cord injury by administering CLP290 because as a known KCC2 activator, CLP290 will upregulate or increase KCC2 activity and ultimately restore proper KCC2 function in the subject with spinal cord injury having impaired Cl- transport. Therefore, the skilled artisan would have had a reasonable expectation of success in treating spinal cord injury by administering CLP290.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Gagnon et al. (“Chloride extrusion enhancers as novel therapeutics for neurological diseases,” Nature Medicine, 2013, 19, 11, 1524-1531, of record), De Koninck et al (US Patent Application 2010/0330586, of record) and Cramer et al. (“The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury,” Molecular Pain, 2008, 4, 36, of record), as applied to claims 1, 12, 72, further in view of Boschert et al. (WO 02/092122, of record).
The instant claims are directed to a method for promoting functional recovery after paralysis in a subject having a spinal cord injury resulting in loss of motor and/or sensory function by administering CLP290 and the second therapeutic, osteopontin.
Gagnon, De Koninck, and Cramer et al. teach as discussed above, however, they fail to disclose osteopontin.
Boschert et al. teach the use of osteopontin for the treatment of neurologic diseases (title and abstract), for example spinal cord trauma (page 28, line 24 to page 29, line 2).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, at the time the claimed invention was made, to have combined osteopontin, as taught by Boschert et al., with CLP290 in the method of treating spinal cord injury, as taught by Gagnon, De Koninck, and Cramer et al.
A person of ordinary skill in the art would have been motivated to combine osteopontin and CLP290 because each have been individually taught to be useful for treating spinal cord injury. Therefore, it would have been obvious to use the therapeutically additive effect of a combination of osteopontin and CLP290 for the treatment of spinal cord injury with a reasonable expectation of success.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... The idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Response to Arguments
Applicant argues that the cited prior art references fail to teach or suggest Applicant’s surprising discovery that overexpression or activation of KCC2 restored stepping ability in mice with spinal cord injury.
This is not persuasive because Applicant has not established why this result is surprising or unexpected. There is no corroborating evidence of record that the state of the art reflects this surprising discovery.
Applicant argues that Cramer relates exclusively to neuropathic pain following spinal cord injury and provides no teaching or suggestion that an increase in KCC2 activity would be effective in increasing motor and/or sensory function below a site of a spinal cord injury. Furthermore, Cramer teaches an increase in NKCC1 protein expression occurred in the lesion epicenter of the spinal cord, which would imply it would be obvious to increase motor and sensory function by decreasing NKCC1 activity.
This is not persuasive because it is not clear as to why NKCC1 is mentioned here. Applicant is reminded that NKCC1 is not mentioned anywhere in the claims, nor is it the same as the claimed KCC2. Regardless, this does not take away from the fact that Cramer teaches that KCC2 was downregulated in rats that underwent spinal cord injury.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant argues that Cramer does not teach that spinal cord injury produces total loss of all motor and sensory function below the level of injury.
This is not persuasive because one of ordinary skill in the art knows that severe spinal cord injury may result in total loss of all motor and sensory function below the level of injury.
Applicant argues that Gagnon and De Koninck do not teach spinal cord injury but peripheral nerve injury and pain associated with spinal cord injury.
This is not persuasive because all the cited prior art references teach treating subjects with spinal cord injury, whether it be for treating pain or nerve injury associated with spinal cord injury or not. The main point is that the subject has spinal cord injury and is being administered a KCC2 activator. Since the cited prior art references teach administering a KCC2 activator, such as CLP290, to a subject with spinal cord injury, the active agent is expected to treat not only pain and nerve injury, but also the spinal cord injury as well.
Conclusion
THIS ACTION IS MADE FINAL. 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623