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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2 June 2025 has been entered.
Priority
This application claims benefit to provisional application No. 62/696,052, filed on 10 July 2018, in a language other than English. An English translation of the non-English language provisional application and a statement that the translation is accurate must be filed in provisional application No. 62/696,052. See 37 CFR 1.78. The English translation and a statement that the translation is accurate required by 37 CFR 1.78 is missing. Accordingly, applicant must supply 1) the missing English translation and a statement that the translation is accurate in provisional application No. 62/696,052 and 2) in the present application, a confirmation that the translation and statement were filed in the provisional application. If 1) and 2) are not filed (or if the benefit claim is not withdrawn) prior to the expiration of the time period set in this Office action, the present application will be abandoned. See 37 CFR 1.78.
The instant application claims benefit to US Provisional Application 62/696,052 which is drawn to administering anti-RGMa antibodies to treat diabetic neuropathies. The instant claims are drawn to treating a broader class of peripheral neuropathies and therefore claims 15, 18, 19, 20, 24, 30, 31, and 32 will receive benefit of PCT/JP2019/027370 filed 10 July 2019 while claims 22, 23, 26 and 27 will received benefit of US Provisional Application 62/696,052 filed 10 July 2018.
Status of the Claims
Claims 1-16 were originally filed 7 January 2021 and the preliminary amendment filed the same day has been entered. Claims 15, 18-20, 22-24, 26, 27, and 30-32 are currently pending and under consideration.
Withdraw Rejections
Upon further consideration an in view of Applicant’s amendments the following rejections:
the 35 USC § 103 rejection of claims 15, 17, and 21-27 over Ertas (as cited on the PTO-892 dated 04/05/2024) and Müller (as cited on the PTO-892 dated 04/05/2024),
the 35 USC § 103 rejection of claims 18-20 and 30-32 over Ertas, Müller, and Hashimoto (as cited on the IDS dated 01/07/2021),
are hereby withdrawn.
Claim Interpretation
Claim 24 is drawn to treating pain symptoms associated with a disease having a peripheral neuropathy wherein the disease having a peripheral neuropathy is selected from a group identical to the group recited in claim 15. The specification discloses,
“In the present invention, diseases having peripheral neuropathies or astrocytic damages which cause pain symptoms are synonyms of the diseases having peripheral neuropathies or astrocytic damages” (see specification pgs. 36-37 para [0077]).
Therefore, claim 24 is interpreted as treating pain symptoms associated with a disease having a peripheral neuropathy as treating pain symptoms associated with those listed in the Markush group. For example treating pain symptoms associated with carpel tunnel syndrome is within the scope of the claim 24, while treating carcinomatous neuropathy of the central nervous system is not within the scope of claim 24.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 15, 18, 24, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent Publication 2004/0102376 A1 (referred to herein as Max-Planck) published 27 May 2004 as evidenced by Stanford Medicine.
Max-Planck discloses a modulator of a polypeptide having or comprising an amino acid sequenced or a functional fragment thereof in a pharmaceutical composition for preventing, alleviating or treating diseases or conditions associated with the degeneration or injury of vertebrate nervous tissue (see Max-Planck pg. 1 para [0001], pg. 3 para [0024]). Specifically, a modulator which binds either chicken RGM or human RGM (i.e., Seq ID NO: 20) (see Max-Planck pg. 2 para [0012, 0015]). It is noted the RGM polypeptide disclosed in Max-Planck Seq ID No: 20 is identical to instant Seq ID No: 1 which is the RGMa polypeptide (see Max-Planck Seq ID No: 20; see instant Seq ID No: 1; see sequence comparison below). A modulator is defined as an inhibitor or activator of RGM function (see Max-Planck pg. 2 para [0014], pg. 3 para [0020])). In a preferred embodiment the disorder of the nervous system comprises degeneration or injury of vertebrate nervous tissue, in particular, neurodegenerative diseases, nerve fiber injuries, and disorders related to nerve fiber loss (see Max-Planck pg. 3 para [0025]). Specifically, neurodegenerative diseases including motor neuron diseases or nerve fiber losses including paresis of nervus facialis, nervus medianus, nervus ulnaris, nervus axillaris, nervus thoracicus longus, nervus radialis and for other peripheral nerves and other acquired and non-acquired diseases of the central and peripheral nervous system (see Max-Planck pg. 3 para [0026]). It is noted the instant claims are drawn to the conditions associated with nerve fiber loss of the particular neurons disclosed in Max-Plank. For example, Max-Planck discloses treating nerve fiber loss of the nervus ulnaris (i.e., ulnar nerve) while the instant specification claims treating cubital ulnar neuropathy (i.e., a condition where the ulnar nerve is compressed and damaged) as evidenced by Stanford Medicine (see Stanford Medicine (2013) Ulnar neuropathy or cubital tunnel syndrome, accessed online, pg. 2, 1st section). Max-Planck discloses the following regarding the modulators or inhibitors of RGM, “in particular envisaged that the inhibitors as defined herein below and comprising, inter alia, anti-RGM antibodies be employed in the medical art to stimulate nerve fiber growth in individuals… most preferably in humans” and “it is particularly preferred that the modulator, preferably the inhibitor of the RGM molecule (or it’s functional fragment or derivative) is an antibody or a fragment or a derivative thereof” (see Max-Plank pgs. 3-4 para [0027], pg. 4 para [0037]). Max-Planck claims Use of a modulator binding to human RGMa (i.e., Seq ID No: 20), for the preparation of a pharmaceutical composition for treating diseases associated with degeneration or injury of vertebrate nervous tissue (see claim 1), wherein said nerve fiber losses are selected from among others nervus ulnaris (see claims 2, 3), and wherein said modulator is an antibody or fragment or a derivative thereof (see claim 9). This is pertinent to claim 15. Claim 24 is drawn to treating the pain symptoms associated with having a peripheral neuropathy (e.g., cubital ulnar syndrome) comprising administering the anti-RGMa neutralizing antibody. Administering the anti-RGMa antibody to a subject with ulnar nerve fiber loss as anticipated by Max-Planck necessarily anticipates treating the symptoms associated with said ulnar nerve fiber loss (i.e., pain).
Regarding claims 18 and 30, Max-Planck discloses the particular antibody is humanized (see Max-Planck pg. 5 para [0039]).
Claims 15, 18, 22-24, 26-27, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2017/210278 A1 (referred to herein as Mueller2, as cited on the IDS dated 7 January 2021, last foreign patent document).
Mueller2 discloses administering of anti-RGMa antibodies to treat pain, including neuropathic pain arising from spinal cord injury (see Mueller2, abstract, pg. 3 para [0015, 0016]). The anti-RGMa antibody is humanized (see Mueller2 pg. 4 para [0017]). Mueller2 discloses there is therapeutic potential of neutralizing inhibitory RGMa after spinal cord injury (SCI) and in particular, contusion or compression injuries (see Mueller2 pg. 5 para [0022]). The anti-RGMa antibodies to be administered are AE12-1, AE12-1-Y, or AE12-1-Y-QL (see Mueller2 pg. 41 para [0041]). Specifically, diabetic neuropathy is disclosed as a pain condition which can be treating with the anti-RGMa antibodies (see Mueller2 pg. 41 para [00141]). It is also noted Mueller2 discloses a method of treating pain in a subject in need thereof wherein the pain is neuropathic pain, specifically postherpetic neuralgia (see Mueller2 pg. 59 claims 6, 7, and 11). This is pertinent to instant claims 15, 18, 22-27, and 30. It is noted claims 23 and 27 are drawn to painful diabetic neuropathy given Mueller2 discloses treating pain associated with diabetic neuropathy it necessarily follows Mueller2 is treating painful diabetic neuropathy.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
In so far as Applicant would argue the above 102 relies on “picking and choosing” from Max-Planck the following USC § 103 rejection is provided.
Claims 15, 18, 24, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Max-Planck as evidenced by Yoon (see Yoon et al. (2010) Ulnar neuropathy with normal electrodiagnosis and abnormal nerve ultrasound. Arch Phys Med Rehabil. 91(2): pgs. 318-320).
Max-Planck discloses a modulator of a polypeptide having or comprising an amino acid sequenced or a functional fragment thereof in a pharmaceutical composition for preventing, alleviating or treating diseases or conditions associated with the degeneration or injury of vertebrate nervous tissue (see Max-Planck pg. 1 para [0001], pg. 3 para [0024]). Specifically, a modulator which binds either chicken RGM or human RGM (i.e., Seq ID NO: 20) (see Max-Planck pg. 2 para [0012, 0015]). It is noted the RGM polypeptide disclosed in Max-Planck Seq ID No: 20 is identical to instant Seq ID No: 1 which is the RGMa polypeptide (see Max-Planck Seq ID No: 20; see instant Seq ID No: 1; see sequence comparison below). A modulator is defined as an inhibitor or activator of RGM function (see Max-Planck pg. 2 para [0014], pg. 3 para [0020])). In a preferred embodiment the disorder of the nervous system comprises degeneration or injury of vertebrate nervous tissue, in particular, neurodegenerative diseases, nerve fiber injuries, and disorders related to nerve fiber loss (see Max-Planck pg. 3 para [0025]). Specifically, neurodegenerative diseases including motor neuron diseases or nerve fiber losses including paresis of nervus facialis, nervus medianus, nervus ulnaris, nervus axillaris, nervus thoracicus longus, nervus radialis and for other peripheral nerves and other acquired and non-acquired diseases of the central and peripheral nervous system (see Max-Planck pg. 3 para [0026]). It is noted the instant claims are drawn to the conditions associated with nerve fiber loss of the particular neurons disclosed in Max-Plank. For example, Max-Planck discloses treating nerve fiber loss of the nervus ulnaris (i.e., ulnar nerve) while the instant specification claims treating cubital ulnar neuropathy (i.e., a condition where the ulnar nerve is compressed and damaged) as evidenced by Yoon (see Yoon pg. 1, 1st para). Max-Planck discloses the following regarding the modulators or inhibitors of RGM, “in particular envisaged that the inhibitors as defined herein below and comprising, inter alia, anti-RGM antibodies be employed in the medical art to stimulate nerve fiber growth in individuals… most preferably in humans” and “it is particularly preferred that the modulator, preferably the inhibitor of the RGM molecule (or it’s functional fragment or derivative) is an antibody or a fragment or a derivative thereof” (see Max-Plank pgs. 3-4 para [0027], pg. 4 para [0037]). Max-Planck claims Use of a modulator binding to human RGMa (i.e., Seq ID No: 20), for the preparation of a pharmaceutical composition for treating diseases associated with degeneration or injury of vertebrate nervous tissue (see claim 1), wherein said nerve fiber losses are selected from among others nervus ulnaris (see claims 2, 3), and wherein said modulator is an antibody or fragment or a derivative thereof (see claim 9).
Therefore an ordinary artisan would use the anti-RGMa antibody as the modulator disclosed in Max-Planck given the antibody is “particularly preferred” (see Max-Planck para [0027 spanning pgs. 3-4, pg. 4 para [0037), pg. 5 para [0041], claim 9) to treat cubital ulnar neuropathy as instantly claimed given nerve fiber loss (i.e., damage) of the nervus ulnaris as disclosed by Max-Planck is understood in the art as synonymous with cubital ulnar syndrome and/or ulnar neuropathy as evidenced by Yoon (see Yoon pg. 1, 1st para).
Regarding claims 18 and 30, Max-Planck discloses the particular antibody is humanized (see Max-Planck pg. 5 para [0039]). Therefore, an ordinary artisan would have humanized the anti-RGMa antibody in order to treat the most preferred subject, humans (see Max-Planck pg. 3 para [0026, last two lines], pg. 4 para [0027]).
Claims 19, 20, 31, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Max-Planck in further view of Hashimoto (see WO2016/175236, as cited on the IDS dated 01/07/2016) as evidenced by either Stanford Medicine (see 35 USC § 102(a)(1) rejection above) or Yoon (see 35 USC § 103 rejection above). It is noted, US Patent Publication 2018/0100012 A1 (as cited on the IDS dated 01/07/2021) will be used as an English translation given Hashimoto and US Patent Publication 2018/0100012 A1 have the same underlying PCT and therefore the same disclosure.
The reasons claims 15 and 24 are anticipated over Max-Planck as evidence by Stanford Medicine are set forth above.
The reasons claims 15 and 24 are obvious over Max-Planck as evidenced by Yoon are set forth above.
Claims 19, 20, 31, and 32 are drawn to limitations in the specific anti-RGMa neutralizing antibody to be administered in a method of treating a particular peripheral neuropathy (see claims 19 and 20) or the treating pain symptoms associated with a particular neuropathy (see claims 31 and 32).
Hashimoto discloses RGMa antibodies with high binding activity which can be used to treat neurological or immunological diseases (see Hashimoto abstract). Specifically anti-RGMa antibodies that bind Seq ID Nos: 26-29 which are identical to instant Seq ID Nos: 36-39 (see claims 19 and 31; see Hashimoto pg. 7 para [0096]). Specifically, antibody B5.116A3 (i.e., r116A3) recognizes amino acids E298-G335 (i.e., instant Seq ID No: 36), N322-E335 (i.e., instant Seq ID No: 37), and L367-A377 (i.e., instant Seq ID No: 39) while antibody B5.70E4 (i.e., r70E4) recognized E298-G335, N322-E335, and P349-T359 (i.e., instant Seq ID No: 38) of human RGMa (see Hashimoto pgs. 16-17 para [0213]). Anti-RGMa antibodies r116A3 and r70E4 were humanized, in particular rH116A3 comprising Seq ID Nos: 30-35, 41 and 42 (see Hashimoto pg. 2 para [0036]), pg. 3 para [0040, 0042], claim 17). It is noted rH116A3 comprises CDRs identical to the instantly claimed Seq ID Nos: 5-10. The humanized anti-RGMa antibody showed equivalent antigen binding properties (i.e., no decrease) compared to the non-humanized version (see Hashimoto pg. 20 para [0243], claim 19). The r116A3 ant5ibody showed significantly improved BBB score 3 or 4 weeks after administration in a spinal cord injury rat model (see Hashimoto pg. 21 para [0251], figure 5B). Furthermore, the humanized version, rH116A3, demonstrated low immunogenicity risk (see Hashimoto pg. 21 para [0255]).
Therefore a person of ordinary skill in the art would substitute the humanized rH116A3 anti-RGMa antibody taught by Hashimoto in a method of paresis of the nervus medianus as taught by Max-Planck given Hashimoto i. demonstrates administration of neutralizing anti-RGMa antibody increased motor function in a spinal cord injury rat model and ii. there was no decrease in antigen binding during the humanization process. This is pertinent to instant claims 19, 20, 31, and 32.
Claims 19, 20, 31, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over WO2017/210278 A1 (referred to herein as Mueller2, as cited on the IDS dated 7 January 2021, last foreign patent document) in further view of Hashimoto (see WO2016/175236, as cited on the IDS dated 01/07/2016). It is noted, US Patent Publication 2018/0100012 A1 (as cited on the IDS dated 01/07/2021) will be used as an English translation given Hashimoto and US Patent Publication 2018/0100012 A1 have the same underlying PCT and therefore the same disclosure.
The reasons claims 15 and 24 are anticipated Mueller2 are set forth above.
The teachings of Hashimoto are set forth above.
Therefore an ordinary artisan would substitute the anti-RGMa antibodies (i.e., AE12-1, AE12-1-Y, or AE12-1-Y-QL) with the humanized rH116A3 anti-RGMa antibody taught by Hashimoto given these are art recognized equivalents for the same purpose (i.e., anti-RGMa antibodies). There is a reasonable expectation of success given Hashimoto i. demonstrates administration of neutralizing anti-RGMa antibody increased motor function in a spinal cord injury rat model and ii. there was no decrease in antigen binding during the humanization process. This is pertinent to instant claims 19, 20, 31, and 32.
Claims 22, 23, 26, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Max-Planck and in further view of and Rota and Morelli (see Rota and Morelli (2016) Entrapment neuropathies in diabetes mellitus. World Journal of Diabetes; 7(17): 342-253) as evidenced by Stanford Medicine (see 35 USC § 102(a)(1) rejection above) and Yoon (see 35 USC § 103 rejection above).
The reasons claims 15 and 24 are either anticipated and/or obvious over Max-Planck as evidence by Stanford Medicine and Yoon are set forth above.
Max-Planck discloses administering anti-RGMa antibodies to treat nerve fiber loss including paresis of the nervus medianus or ulnaris (see Max-Planck pg. 3 para [0026], pgs. 3-4 para [0027], pg. 4 para[0037]); see above). Carpel tunnel syndrome and cubital ulnar neuropathy are the syndromes associated with nerve fiber loss of the nervus medianus and ulnaris as evidence by Stanford Medicine and Yoon (see Stanford Medicine pg. 2, 1st section; see Yoon pg. 1, 1st para).
Rota and Morelli teaches, “Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in diabetes mellitus (DM)” (see Rota and Morelli abstract). Diabetic neuropathy is the most common form of neuropathy in Western countries (i.e., up to 90%) (see Rota and Morelli pg. 343, 1st col. 1st para). Subclinical neuropathy at the elbow (i.e., cubital ulnar neuropathy) was diagnosed in “a remarkably high percentage, i.e., 34%, of DM patients, suggesting that the ulnar nerve is very susceptible to focal entrapment in DM, as is the median nerve. These findings and others (see carpal tunnel syndrome (CTS) and ulnar entrapments), suggest that EN in DM, mostly at the upper limbs, are not late complications, but rather early neurophysiological abnormalities, where the frequency increases with the disease duration and/or in the presence of generalized diabetic neuropathy” (see Rota and Morelli pg. 344, 1st col. 1st para).
Therefore a person of ordinary skill in the art would substitute a mammal with nerve fiber loss of the nervus medianus (i.e., carpal tunnel syndrome) or ulnaris (i.e., cubital ulnar neuropathy) as taught by Max-Planck with a mammal with the carpal tunnel syndrome or cubital ulnar neuropathy as a result of DM given the syndromes are the same.
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 15, 18-22, 24, 26, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10, 11, and 18-21 of copending Application No. 17/792,673 (referred to herein as ‘673 application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Applicant has argued the non-statutory double patenting rejection be held in abeyance until the present application is otherwise in condition for allowance or the obviousness rejection is no longer provisional in nature (see Response to Final received 2 June 2025, referred to herein as Remarks pg. 16 (A), para III). Therefore, given the instant application is not in a condition for allowance (see above) the non-statutory double patenting rejections is hereby maintained.
Claims 15, 18-20, 24, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 10, 11, and 13 of U.S. Patent No. ‘346 (as cited on the PTO-892 dated 04/05/2024) and Mazan (as cited on the PTO-892 mailed 16 December 2024). Although the claims at issue are not identical, they are not patentably distinct from each other.
Applicant's arguments filed 2 June 2025 have been fully considered but they are not persuasive. Applicant argues the ‘346 patent and Mazan are drawn to treatment of Sjögren’s syndrome which is not related to the peripheral neuropathies recited in the pending claims (see pg. 17, 2nd para).
Instant claims 15 and 24 are drawn to methods of treating a disease or pain associated with a disease having a peripheral neuropathy by administering a neutralizing RGMa antibody to a mammal in need thereof wherein the disease having a peripheral neuropathy is chronic inflammatory demyelinating polyneuropathy (CIDP) or neuropathy associated with connective tissue diseases. The ‘346 patent claims a pharmaceutical composition for treating Sjögren’s syndrome. Mazan teaches Primary Sjögren’s syndrome (pSS) is an autoimmune connective tissue disease (see Mazan abstract) wherein 2-60% of patients suffer from a peripheral neuropathy including, chronic inflammatory demyelinating polyneuropathy (CIDP) (see Mazan pg. 100, 2nd col. last para).
Therefore an ordinary artisan would find it obvious to administer the “pharmaceutical composition for use in treating Sjögren’s syndrome” as claimed in the ‘346 patent to a Sjögren’s syndrome patient experiencing peripheral neuropathy given these particular subjects comprise more than 50% of the patient population.
The non-statutory double patenting rejection of claims 15, 18-20, 24, and 30-32 is hereby maintained.
New Double Patenting Rejections
Claims 15, 18-20, 24, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of U.S. Patent No. ‘388 (as cited on the PTO-892 dated 04/05/2024) and US Patent Publication 2004/0102376 A1 (referred to herein as Max-Planck) as evidenced by Stanford Medicine. Although the claims at issue are not identical, they are not patentably distinct from each other.
The ‘388 patent claims an anti-RGMa antibody comprising identical CDRs to the instantly elected species (see ‘388 patent Seq ID Nos: 30-35; see instant Seq ID Nos: 5-10) and wherein the antibody is humanized (see ‘388 patent claims 1a and 7, see instant claims 20a and 32a). It is noted, the ‘388 application is silent regarding the epitope; however, given the CDRs are identical and the primary determinants for binding it necessarily follows the ‘388 patent antibody binds to one of the instantly claimed sequences and is neutralizing (see instant claims 17, 19, 29 and 31). The ‘388 patent also recites a method for treating neurotrauma comprising administering a pharmaceutical composition comprising the anti-RGMa antibody (see ‘388 patent claims 9 and 14).
Max-Planck discloses a modulator of RGMa in a pharmaceutical composition for preventing, alleviating or treating diseases or conditions associated with the degeneration or injury of vertebrate nervous tissue (see Max-Planck pg. 1 para [0001], pg. 3 para [0024]). Specifically, a modulator which binds either chicken RGM or human RGM (i.e., Seq ID NO: 20) (see Max-Planck pg. 2 para [0012, 0015]). A preferred modulator is an antibody or a fragment or a derivative thereof (see Max-Plank pgs. 3-4 para [0027], pg. 4 para [0037]). In a preferred embodiment the disorder of the nervous system comprises degeneration or injury of vertebrate nervous tissue, in particular, neurodegenerative diseases, nerve fiber injuries, and disorders related to nerve fiber loss (see Max-Planck pg. 3 para [0025]). Specifically, neurodegenerative diseases including motor neuron diseases or nerve fiber losses including paresis of nervus facialis, nervus medianus, nervus ulnaris, nervus axillaris, nervus thoracicus longus, nervus radialis and for other peripheral nerves and other acquired and non-acquired diseases of the central and peripheral nervous system (see Max-Planck pg. 3 para [0026]). It is noted the instant claims are drawn to the conditions associated with nerve fiber loss of the particular neurons disclosed in Max-Plank. For example, Max-Planck discloses treating nerve fiber loss of the nervus ulnaris (i.e., ulnar nerve) while the instant specification claims treating cubital ulnar neuropathy (i.e., a condition where the ulnar nerve is compressed and damaged) as evidenced by Stanford Medicine (see Stanford Medicine (2013) Ulnar neuropathy or cubital tunnel syndrome, accessed online, pg. 2, 1st section).
Therefore, an ordinary artisan would have substituted the subject with neurotrauma claimed in the ‘388 patent with a subject with carpal tunnel syndrome or cubital ulnar neuropathy as taught by Max-Planck given Max-Planck discloses using anti-RGMa antibodies to treat injury of vertebrate nervous tissue including nerve fiber loss of the nervus medianus and nervus ulnaris, terms known to be synonymous with carpal tunnel syndrome and cubital ulnar neuropathy. This is pertinent to claim 15. Claim 24 is drawn to treating the pain symptoms associated with having a peripheral neuropathy (e.g., cubital ulnar syndrome) comprising administering the anti-RGMa neutralizing antibody. Administering the anti-RGMa antibody to a subject with ulnar nerve fiber loss as anticipated by Max-Planck necessarily anticipates treating the symptoms associated with said ulnar nerve fiber loss (i.e., pain).
Claims 15, 18-20, 22-24, 26, 27, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of U.S. Patent No. ‘388 (as cited on the PTO-892 dated 04/05/2024), US Patent Publication 2004/0102376 A1 (referred to herein as Max-Planck), and Rota and Morelli as evidenced by Stanford Medicine. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reasons claims 15 and 24 are obvious over the ‘388 patent and Max-Planck are set forth above.
The teachings of Rota and Morelli are set forth above
Therefore, an ordinary artisan would have substituted the subject with neurotrauma claimed in the ‘388 patent with a subject with carpal tunnel syndrome or cubital ulnar neuropathy as taught by Max-Planck given Max-Planck discloses using anti-RGMa antibodies to treat injury of vertebrate nervous tissue including nerve fiber loss of the nervus medianus and nervus ulnaris, terms known to be synonymous with carpal tunnel syndrome and cubital ulnar neuropathy. Furthermore, an ordinary artisan would substitute a mammal with nerve fiber loss of the nervus medianus (i.e., carpal tunnel syndrome) or ulnaris (i.e., cubital ulnar neuropathy) as taught by Max-Planck with a mammal with the carpal tunnel syndrome or cubital ulnar neuropathy as a result of DM given the syndromes are the same.
Claims 15, 18-20, 24, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 10, 11, and 13 of U.S. Patent No. ‘346 (as cited on the PTO-892 dated 04/05/2024) and Rota and Morelli.
The ‘346 patent recites an anti-RGMa antibody comprising identical CDRs to the instantly elected species (see ‘346 patent Seq ID Nos: 30-35; see instant Seq ID Nos: 5-10) wherein the antibody is humanized (see ‘346 patent claims 1-3, see instant claims 20a and 32a). It is noted, the ‘346 patent is silent on the epitope; however, given the CDRs are identical and the CDRs are the primary determinants for binding it necessarily follows the ‘346 patent antibody binds to one of the instantly claimed sequences and neutralizes (see instant claims 17, 19, 29 and 31). In addition, the ‘346 patent recites a pharmaceutical composition for use in treating immunological diseases, in particular type I (insulin dependent) diabetes mellitus (see ‘346 patent claims 10, 11, and 13). The ‘346 patent recites an identical anti-RGMa antibody (see instant claims 18-20 and 30-32) in a pharmaceutical composition for the treatment of type I diabetes mellitus.
The teachings of Rota and Morelli are set forth above.
Therefore, a person of ordinary skill in the art would substitute a type I diabetic mellitus subject for a type I diabetic mellitus subject with diabetic neuropathy specifically painful diabetic neuropathy and/or asymptomatic diabetic neuropathy given diabetic neuropathy is “the most common form of neuropathy in Western countries, with a wide prevalence in literature, ranging from 5%-90%”, “entrapment neuropathies (EN) are remarkably common in DM at any stage and may be asymptomatic”, “the majority of EN in DM are chronic and often asymptomatic” (see Rota and Morelli pg. 343, 1st col. 1st para, 2nd col. 3rd-5th para).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 27 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 27 is drawn to wherein the disease having a peripheral neuropathy is diabetic neuropathy specifically asymptomatic diabetic neuropathy. However claim 27 depends from claims 24 and 26 which are drawn to treating pain symptoms associated with a disease having peripheral neuropathy. It is unclear how a method for treating pain symptoms (i.e., has at least 1 symptom) can comprise an asymptomatic (i.e., no symptoms) diabetic neuropathy.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 27 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 27 is drawn to wherein the disease having a peripheral neuropathy is diabetic neuropathy specifically painful diabetic neuropathy. However claim 27 depends from claims 24 and 26 which are drawn to treating pain symptoms associated with a disease having peripheral neuropathy (see claim 24) wherein the peripheral neuropathy is specifically diabetic neuropathy (see claim 26); therefore it necessarily follows claim 26 is drawn to treating painful diabetic neuropathy. Thus, claim 27 does not further limit claim 26.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Sequence Comparison
(Qy) is Instant Seq ID No: 1 compared to (Db) Max-Planck Seq ID No: 20
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597
534
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Conclusion
No claim allowed.
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/H.A.P./Examiner, Art Unit 1644 /AMY E JUEDES/Primary Examiner, Art Unit 1644