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 .
Election/Restrictions
Applicant’s election without traverse of Group I and species of a hydrophilic linker, OTL38, and a patient with spinal trauma in the reply filed on July 16, 2026 is acknowledged. Because OTL38 consists of a folate ligand (pteroyl), a tyrosinate linker, and a near infrared (NIR) dye S0456, OTL38 reads on claims 1, 2, 8-10, 13, 16, 23, 39, and 40.
Claim Objections
Claim 39 is objected to because of the following informalities:
“…the payload to the to the patient…” should read “…the payload to the patient.…”
Appropriate correction is required.
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.
Claims 1, 2, 8-10, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023).
Regarding claims 1 and 13, Low discloses a method of increasing the endosomal accumulation and escape of a therapeutic agent or an imaging agent, the method comprising the step of administering with an effective amount of a conjugate (claim 14). Low discloses that the therapeutic agent can be a central nervous system (CNS) agent (¶ 213), and that a folate-targeted conjugate can be used for the imaging or treatment of an inflammatory disease at a site of inflammation (¶ 186). Thus, Low inherently or explicitly teaches using the conjugate to administer an effective amount of a conjugate comprising folate targeted ligand and therapeutic or imaging agent to deliver the agent to a patient with inflammation in the CNS. Low discloses linkers such as releasable linkers can be used to prepare ligand-therapeutic agent or ligand-imaging agent compounds (¶ 227).
Regarding claims 2 and 8-10, Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, which comprise a folate receptor-alpha (FRα)-targeting ligand (folate analog) conjugated to a fluorescent near infrared (NIR) dye (¶ 318). Low discloses that the NIR dye can be S0456 (¶ 224).
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.
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.
Claims 1, 2, 8-10, 13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023) in view of Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023).
As discussed above, regarding claims 1 and 13, Low discloses a method of increasing the endosomal accumulation and escape of a therapeutic agent or an imaging agent, the method comprising the step of administering with an effective amount of a conjugate (claim 14). Low discloses that the therapeutic agent can be a central nervous system (CNS) agent (¶ 213), and that a folate-targeted conjugate can be used for the imaging or treatment of an inflammatory disease at a site of inflammation (¶ 186). Thus, Low inherently or explicitly teaches using the conjugate to administer an effective amount of a conjugate comprising folate targeted ligand and therapeutic or imaging agent to deliver the agent to a patient with inflammation in the CNS. Further, since Low discloses the same conjugate compound as claimed, the compound predictably can be used for the same claimed application, namely delivering a payload to a patient with inflammation in the CNS or imaging an area of a CNS patient affected by the inflammation. Low discloses linkers such as releasable linkers can be used to prepare ligand-therapeutic agent or ligand-imaging agent compounds (¶ 227). Regarding claims 2 and 8-10, Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, which comprise a folate receptor-alpha (FRα)-targeting ligand (folate analog) conjugated to a fluorescent near infrared (NIR) dye (¶ 318). Low discloses that the NIR dye can be S0456 (¶ 224).
Low does not disclose that the payload is transported to an eye.
Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of Low to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans. Accordingly, applying the teachings of Leamon to the method of Low constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders claim 16 obvious.
Claims 23, 39, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023) in view of Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Low is discussed above.
Low does not disclose a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient.
Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of Low to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects. Accordingly, applying the teachings of Fernández-Villa to the method of Low constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders claims 23, 39, 40 obvious.
Claims 1, 2, 8-10, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Low et al. (US 2014 0271482; cited on PTO-892; herein after “Low 2014”) in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023).
Regarding claims 1, 2, and 8-10, Low 2014 discloses a method of performing image guided surgery on a subject comprising administering a composition comprising a compound comprising a folate derivative, a linker, and a dye (claims 1 and 37). Low 2014 discloses that the compound can be OTL-0038 comprising pteroyl ligand, tyrosine linker, and S0456 dye for applications such as image guided surgery, tumor imaging, and inflammatory diseases (¶ 16). Low 2014 discloses that the compound can be used for imaging diseases such as neurodegenerative diseases and immunologic diseases (claim 29).
Low 2014 does not disclose a patient with inflammation in the CNS (instant claim 1) and imaging an area of the CNS patient affected by inflammation (instant claim 13).
As discussed above, Low discloses a method of increasing the endosomal accumulation and escape of a therapeutic agent or an imaging agent, the method comprising the step of administering with an effective amount of a conjugate (claim 14). Low discloses that the therapeutic agent can be a CNS agent (¶ 213), and that a folate-targeted conjugate can be used for the imaging or treatment of an inflammatory disease at a site of inflammation (¶ 186). Thus, Low inherently or explicitly teaches using the conjugate to administer an effective amount of a conjugate comprising folate targeted ligand and therapeutic or imaging agent to deliver the agent to a patient with inflammation in the CNS.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the method of the Low 2014 for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of Low 2014 to a patient with inflammation in the CNS in order to expand the applications of the method. Since Low 2014 discloses the same conjugate compound as claimed, the compound predictably can be used for the same claimed application, namely delivering a payload to a patient with inflammation in the CNS or imaging an area of a CNS patient affected by the inflammation.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Low 2014 and Low as applied to claims 1, 2, 8-10, and 13, and further in view of Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023).
Low 2014 and Low are discussed above.
Neither Low 2014 nor Low discloses that the payload is transported to an eye.
As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of Low 2014 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans. Accordingly, applying the teachings of Leamon to the method of Low 2014 constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders claim 16 obvious.
Claim 23, 39, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Low 2014 and Low as applied to claims 1, 2, 8-10, and 13, and further in view of Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Low 2014 and Low are discussed above.
Neither Low 2014 nor Low disclose a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient.
As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of Low 2014 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects. Accordingly, applying the teachings of Fernández-Villa to the method of Low constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders claims 23, 39, 40 obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 9 of U.S. Patent No. US 8,546,425 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claims 1 and 9 of the ‘425 recite a method for treating a population of pathogenic cells in a patient, the method comprising administering a therapeutically effective amount of the conjugate comprising an antifolate (ligand), a ligand, and a drug (payload). Claims of the ‘425 do not recite a patient with inflammation in the CNS. Claims of the ‘425 do not recite an imaging agent such as S0456 as a payload. Claims of the ‘425 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘425 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘425 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘425 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘425 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘425 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘425 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 7 of U.S. Patent No. US 9,333,270 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claim 1 of the ‘270 recites a method of optical imaging of a biological tissue that expresses a folate receptor, the method comprising contacting the biological tissue with a composition comprising a compound comprising a folate derivative, a linker, and a dye. Claims 6 and 7 recite that the biological tissue that expresses a folate receptor can have a disease such as neurodegenerative diseases and immunologic diseases. Claims of the ‘270 do not recite a method of delivering a payload to a patient with inflammation in the CNS. Claims of the ‘270 do not recite NIR dye such as S0456 as a payload. Claims of the ‘270 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘270 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘270 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘270 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘270 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘270 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘270 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 9,629,918 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claim 1 of the ‘918 recites a folate receptor alpha selective binding ligand drug conjugate comprising a folate receptor alpha selective binding ligand, a linker, and an imaging agent. Claims of the ‘918 do not recite a method of delivering a payload to a patient with inflammation in the CNS. Claims of the ‘918 do not recite NIR dye such as S0456 as a payload. Claims of the ‘918 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘918 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘918 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘918 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘918 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘918 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘918 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 9,549,992 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claim 1 of the ‘992 recites a conjugate comprising an antifolate, a linker, and a drug. Claims of the ‘992 do not recite a method of delivering a payload to a patient with inflammation in the CNS. Claims of the ‘992 do not recite an imaging agent such as NIR dye S0456 as a drug. Claims of the ‘992 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘992 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘992 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘992 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘992 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘992 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘992 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 10,363,250 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claim 1 of the ‘250 recites a method for treating a population of cancer cells in a patient, the method comprising administering to the patient a therapeutically effective amount of a conjugate comprising an antifolate, a linker, and a drug. Claims of the ‘250 do not recite a patient with inflammation in the CNS. Claims of the ‘250 do not recite an imaging agent such as NIR dye S0456 as a drug. Claims of the ‘250 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘250 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘250 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘250 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘250 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘250 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘250 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 14 of U.S. Patent No. US 10,406,238 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claims 1, 2, and 14 of the ‘238 recites a method of increasing the endosomal accumulation and escape of a therapeutic agent or an imaging agent, the method comprising the step of administering with the therapeutic agent or the imaging agent an effective amount of the conjugate comprising a folate receptor binding ligand, a linker, and an imaging agent. Claims of the ‘238 do not recite a patient with inflammation in the CNS. Claims of the ‘238 do not recite a NIR dye such as S0456 as an imaging agent. Claims of the ‘238 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘238 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘238 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘238 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘238 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘238 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘238 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of U.S. Patent No. US 11,219,622 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claims 1 and 12 of the ‘622 recites a method for treating a pathogenic population of cells in a patient, the method comprising administering an effective amount of the conjugate comprising an antifolate, a linker, and a drug. Claims of the ‘622 do not recite a patient with inflammation in the CNS. Claims of the ‘622 do not recite a imaging agent such as NIR dye S0456 as a drug. Claims of the ‘622 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘622 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘622 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘622 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘622 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘622 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘622 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
Claims 1, 2, 8-10, 13, 16, 23, 39, and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, and 19 of copending Application No. 18/560,675 in view of Low et al. (US 2019 0298843; cited on IDS filed July 6, 2023), Leamon et al. (US 2013 0203680; cited on IDS filed July 6, 2023), and Fernández-Villa et al. (International journal of molecular sciences, 2018; cited on PTO-892).
Regarding claims 1, 2, 8-10, and 13, claim 1 of the ‘675 recites a conjugate comprising an a folate receptor-targeting ligand, a linker, and an active agent. Claims 18 and 19 of the ‘675 recite that the active agent can be ab optical imaging agent such as S0456. Claims of the ‘675 do not recite a patient with inflammation in the CNS. Claims of the ‘675 do not recite that the conjugate is OTL38. As discussed above, Low discloses that the conjugate can be used to administer to a patient with inflammation in the CNS (¶ 186; ¶ 213). Low discloses that the payload can be a NIR dye such as S0456 (¶ 224). Low discloses that the conjugate can be the fluorescent imaging ligand OTL38, a FRα-targeting ligand conjugated to a fluorescent NIR dye (¶ 318). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘675 by utilizing an imaging agent as a payload, such as OTL38, for diagnosing a patient with inflammation in the CNS. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Low teaches that such a folate-imaging agent conjugate can be used for imaging an area of a CNS patient affected by the inflammation. Further, a person of ordinary skill in the art would have been motivated to apply the method of the ‘675 to a patient with inflammation in the CNS in order to expand the applications of the method.
Regarding claim 16, claims of the ‘675 do not recite that the payload is transported to an eye. As discussed above, Leamon discloses a method of using folate conjugates for treating inflammatory diseases of the eye (abstract). Leamon discloses that folate conjugates can be used to treat inflammatory diseases of the eye by targeting inflammatory cells that overexpress the folate receptor (¶ 6). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘675 to transport the folate conjugated payload to an eye for eye-targeted therapy or diagnosis. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Leamon teaches that folate conjugation can be used to target the inflammatory cells of the eye for targeted drug delivery to the eye. Further, a person of ordinary skill in the art would have been motivated to monitor CNS inflammation through the eyes to allow non-invasive, live tracking of immune cell activity and neuroinflammatory flare-ups in vivo, much faster and cheaper than standard brain scans.
Regarding claims 23, 39, 40, claims of the ‘675 do not recite a specific type of disease such as spinal trauma and that delivering the payload to a patient having neurotrauma constitutes treating the patient. As discussed above, Fernández-Villa discloses that folate receptor 1 expression levels increase after a spinal cord injury (spinal trauma) (page 12, ¶ 1). Fernández-Villa discloses that a folate-conjugated drug delivery system can be used for targeted delivery of a drug to a site for targeted therapy or diagnosis (page 3, Table 1; page 5, Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of the ‘675 to treat a patient having spinal trauma. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Fernández-Villa teaches that folate conjugation can be used to target and treat the patient having spinal trauma. Further, a person of ordinary skill in the art would have been motivated to utilize the conjugate of Low in order to expand the applications of the conjugate. A person of ordinary skill in the art would have been motivated to use folate conjugation in spinal trauma to actively target inflammatory cells that overexpress folate receptors at the lesion site in order to deliver therapeutic or diagnostic agents precisely where needed while minimizing systemic side effects.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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