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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/30/2025 has been entered.
DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Amendment after Final office action filed on 10/30/2025 is acknowledged.
3. Claim filed on 10/30/2025 is acknowledged.
4. Claims 4-7, 14-16 and 18-28 have been cancelled.
5. Claims 1-3, 8-13, 17, 29 and 30 are pending in this application.
6. Claims 9, 10, 13 and 30 remain withdrawn from consideration as being drawn to non-elected species.
7. Applicant elected without traverse of a composition in the form of hydrogel comprising hyaluronic acid, a laminin polypeptide as set forth in SEQ ID NO: 1, vitamin E as antioxidant and Copolymer 1 as additional agent as species of composition; and spinal cord injury caused by a trauma and not by a disease as species of nerve injury from claims 8-13 in the reply filed on 11/4/2024.
Restriction requirement was deemed proper and made FINAL in the previous office actions. The instant claims 1-3, 8-13, 17, 29 and 30 are drawn to a method of deferred treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting at least 1 week after onset or diagnosis of the nerve injury in the subject a composition comprising hyaluronic acid, laminin polypeptide, vitamin E, and copolymer 1 at or near the nerve injury of the subject, thereby treating the nerve injury in the subject. A search was conducted on the elected species; and prior art was found. Claims 9, 10, 13 and 30 remain withdrawn from consideration as being drawn to non-elected species. Claims 1-3, 8, 11, 12, 17 and 29 are examined on the merits in this office action.
Withdrawn Objections and Rejections
8. Objection to claims 16 and 17 is hereby withdrawn in view of Applicant’s amendments to the claim.
9. Rejection to claims 1-3, 8, 11, 12, 14-19 and 29 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 13-21 and 23-26 of Application No. 16/767189 in view of Rochkind et al (US 2011/0104225 A1, filed with IDS), Eisenbach-Schwartz et al (WO 2006/057003 A2, filed with IDS) and Coumans et al (The Journal of Neuroscience, 2001, 21, pages 9334-9344, cited and enclosed in the previous office action) is hereby withdrawn in view of Applicant’s abandonment of Application No. 16/767189.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 103
10. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
11. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
12. (Revised due to Applicant’s amendment to the claim) Claims 1-3, 8, 11, 12, 17 and 29 remain rejected under 35 U.S.C. 103 as being unpatentable over Rochkind et al (US 2011/0104225 A1, filed with IDS) in view of Wang et al (Interface Focus, 2012, 2, pages 278-291, filed with IDS), Kabu et al (Journal of Controlled Release, 2015, 219, pages 141-154, filed with IDS), Eisenbach-Schwartz et al (WO 2006/057003 A2, filed with IDS) and Coumans et al (The Journal of Neuroscience, 2001, 21, pages 9334-9344, cited and enclosed in the previous office actions).
The instant claims 1-3, 8, 11, 12, 17 and 29 are drawn to a method of deferred treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting at least 1 week after onset or diagnosis of the nerve injury in the subject a composition comprising hyaluronic acid, laminin polypeptide, vitamin E, and copolymer 1 at or near the nerve injury of the subject, thereby treating the nerve injury in the subject.
Rochkind et al, throughout the patent, teach a composition-of-matter comprising hyaluronic acid, a laminin polypeptide and an antioxidant, wherein the composition-of-matter is in the form of hydrogel, wherein the laminin polypeptide is SEQ ID NO: 3 consisting of the amino acid sequence KSIKVAVRSYIGSRCV (identical to the laminin polypeptide of instant SEQ ID NO: 1), and wherein the composition-of-matter induces neuronal cell differentiation of primary fetal rat brain cells derived from cerebral hemispheres of rat; and a method of treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting the composition-of-matter at or near the nerve injury of the subject, wherein the nerve injury is caused by trauma, and wherein the nerve injury can be CNS lesions, for example, Abstract; Figures 2 and 3; page 1, paragraphs [0006], [0008], [0011], [0014], [0015], [0019] and [0020]; page 2, paragraphs [0032], [0041], [0043], [0045] and [0046]; page 7, paragraph [0102]; page 8, paragraphs [0112] and [0113]; page 11, Example 2, in particular paragraphs [0151], [0162] and [0163]; and claims 5, 7-11, 13 and 24. It meets the limitations of the nerve injury, the site of implanting, hyaluronic acid, and laminin polypeptide recited in instant claim 1; and the limitations of instant claims 8, 11, 17 and 29. Rochkind et al further teach the antioxidant in the composition-of-matter can be vitamin E, for example, page 6, paragraph [0069]. It meets the limitation of vitamin E recited in instant claim 1. Therefore, in view of the teaching of Rochkind et al as a whole, one of ordinary skilled in the art would understand and reasonably expect a composition-of-matter comprising hyaluronic acid, a laminin polypeptide of SEQ ID NO: 3 (identical to the laminin polypeptide of instant SEQ ID NO: 1) and vitamin E as an antioxidant, wherein the composition-of-matter is in the form of hydrogel; and using such composition for treating nerve injury, such as CNS lesions in a subject in need thereof.
The difference between the reference and instant claims 1-3, 8, 11, 12, 17 and 29 is that the reference does not explicitly teach a composition in the form of hydrogel comprising hyaluronic acid, a laminin polypeptide as set forth in SEQ ID NO: 1, vitamin E as antioxidant and Copolymer 1 as additional agent as the elected species of composition; spinal cord injury caused by a trauma and not by a disease as the elected species of nerve injury; copolymer 1 and the deferred treatment schedule recited in instant claim 1; and the limitations of instant claims 2, 3 and 12.
However, Wang et al, throughout the literature, teach hydrogel comprising hyaluronic acid (HA) and laminin improves neural regeneration, and can be used for treating damage to CNS, such as spinal cord injury (SCI), for example, Abstract; page 278, left column, the 1st paragraph in Section “1. INTRODUCTION”; page 280, right column, the 1st paragraph in Section “2.1.3. Modification of engineered extracellular matrix components”; pages 282-283, Section “3.3. Modification of hyaluronic acid hydrogels”; and page 284, Section “3.4.2. Delivery of neurotrophic factors using hyaluronic acid-based scaffolds”.
Furthermore, Kabu et al, throughout the literature, teach current treatments used for SCI can be categorized mainly as neuroprotective or neuroregenerative in nature; early interventions following primary injury are aimed at preventing cascades of secondary degeneration, particularly drug and neuroprotective therapies, whereas at a chronic stage, it is primarily regenerative therapy such as cell-based therapies, tissue engineering, either through remyelination and/or axonal sprouting to establish neuronal connectivity and achieve functional recovery; and the timing of therapeutic interventions as one of the important factors contributing to success of treating SCI, for example, Abstract; and pages142-143, Figure 1 and Section “1.2. Therapeutic and regenerative strategies for treatment of spinal cord injury”. Kabu et al further teach high doses of antioxidants, vitamins C and E (100 mg/kg/day), in an SCI model have shown to lessen the inflammatory response; and the role of SOD in neuroprotection against oxidative stress in SCI, for example, pages 144-145, Sections “1.4.6. Targeting oxidative stress” and “1.4.6.1. Antioxidant enzymes”. Kabu et al also teach hydrogel comprising hyaluronic acid and laminin for treating SCI, for example, page 148, Section “3.1. Hydrogels for tissue engineering”. Therefore, in view of the combined teachings of Rochkind et al, Wang et al and Kabu et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, and vitamin E as an antioxidant; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI. It reads on spinal cord injury caused by a trauma and not by a disease as the elected species of nerve injury.
In addition, Eisenbach-Schwartz et al, throughout the patent, teach copolymer 1 for treating nerve injury of either PNS or central nervous system (CNS), such as SCI, for example, Abstract; page 1, lines 6-10; page 36, lines 3-8; and page 37, lines 1-10. Therefore, in view of the combined teachings of Rochkind et al, Wang et al, Kabu et al and Eisenbach-Schwartz et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI. It reads on a composition in the form of hydrogel comprising hyaluronic acid, a laminin polypeptide as set forth in SEQ ID NO: 1, vitamin E as antioxidant and Copolymer 1 as additional agent as the elected species of composition. And, the MPEP states: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…” (see MPEP § 2144.06).
Furthermore, Coumans et al, throughout the literature, teach that in comparison to applied acutely, deferred treatment of SCI with neurotrophins (applied 2-4 weeks after the onset of SCI) dramatically increases regeneration from supraspinal pathways and recovery of motor function, for example, Abstract; page 9335, left column, the 2nd paragraph; page 9336, right column, the 2nd, 3rd and 4th paragraphs; and page 9343, the paragraph bridging the left and right columns. Coumans et al further teach environmental factors play a role in restricting axonal growth within a mature CNS environment, and the environment at the injury site may become more favorable for axonal growth over time after injury compared with the acutely injured spinal cord; and there may be differences in the ability of neurons themselves to mount a regenerative response, for example, page 9342, right column, the 2nd and 3rd paragraphs.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Rochkind et al, Wang et al, Kabu et al, Eisenbach-Schwartz et al and Coumans et al to develop a method of deferred treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI, such as 2-4 weeks after the onset of SCI.
One of ordinary skilled in the art would have been motivated to combine the teachings of Rochkind et al, Wang et al, Kabu et al, Eisenbach-Schwartz et al and Coumans et al to develop a method of deferred treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI, such as 2-4 weeks after the onset of SCI, because Wang et al, throughout the literature, teach hydrogel comprising hyaluronic acid (HA) and laminin improves neural regeneration, and can be used for treating damage to CNS, such as SCI. Kabu et al, throughout the literature, teach current treatments used for SCI can be categorized mainly as neuroprotective or neuroregenerative in nature; early interventions following primary injury are aimed at preventing cascades of secondary degeneration, particularly drug and neuroprotective therapies, whereas at a chronic stage, it is primarily regenerative therapy such as cell-based therapies, tissue engineering, either through remyelination and/or axonal sprouting to establish neuronal connectivity and achieve functional recovery; and the timing of therapeutic interventions as one of the important factors contributing to success of treating SCI. Kabu et al further teach high doses of antioxidants, vitamins C and E (100 mg/kg/day), in an SCI model have shown to lessen the inflammatory response; and the role of SOD in neuroprotection against oxidative stress in SCI. Kabu et al also teach hydrogel comprising hyaluronic acid and laminin for treating SCI. Therefore, in view of the combined teachings of Rochkind et al, Wang et al and Kabu et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, and vitamin E as an antioxidant; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI. Eisenbach-Schwartz et al, throughout the patent, teach copolymer 1 for treating nerve injury of either PNS or CNS, such as SCI. Therefore, in view of the combined teachings of Rochkind et al, Wang et al, Kabu et al and Eisenbach-Schwartz et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI. Furthermore, the MPEP states: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…” (see MPEP § 2144.06). And Coumans et al, throughout the literature, teach that in comparison to applied acutely, deferred treatment of SCI with neurotrophins (applied 2-4 weeks after the onset of SCI) dramatically increases regeneration from supraspinal pathways and recovery of motor function. Coumans et al further teach environmental factors play a role in restricting axonal growth within a mature CNS environment, and the environment at the injury site may become more favorable for axonal growth over time after injury compared with the acutely injured spinal cord; and there may be differences in the ability of neurons themselves to mount a regenerative response.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Rochkind et al, Wang et al, Kabu et al, Eisenbach-Schwartz et al and Coumans et al to develop a method of deferred treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI, such as 2-4 weeks after the onset of SCI.
Response to Applicant's Arguments
13. Applicant argues that there is no motivation to combine the cited prior art references and also no reasonable expectation of success for delayed treatment of SCI injuries with the HA hydrogel developed from the combined teachings of the cited prior art references by arguing about each of the cited references individually; and the number of references cited in instant rejection.
14. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant's arguments about instant rejection, the Examiner agrees that none of the cited references individually teaches or suggests the method recited in instant claims 1-3, 8, 11, 12, 17 and 29; and none of the cited references anticipates the method recited in instant claims 1-3, 8, 11, 12, 17 and 29. However, the Examiner would like to point out that instant claims 1-3, 8, 11, 12, 17 and 29 are rejected under 35 U.S.C. 103 (obviousness type), and the rejection is based on the combined teachings of Rochkind et al, Wang et al, Kabu et al, Eisenbach-Schwartz et al and Coumans et al; therefore, it is not necessary for each of the cited references to teach all the limitations of instant claims. Furthermore, the Examiner would like to point out that the MPEP states "One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references…" (see MPEP § 2145 IV).
In response to Applicant's arguments that there is no motivation to combine the cited prior art reference and also no reasonable expectation of success for delayed treatment of SCI injuries with the HA hydrogel developed from the combined teachings of the cited prior art references:
First, the Examiner understands that none of the cited references teach the composition recited in instant claims. However, in the instant case, as stated in Section 12 above, in view of the teaching of Rochkind et al as a whole, one of ordinary skilled in the art would understand and reasonably expect a composition-of-matter comprising hyaluronic acid, a laminin polypeptide of SEQ ID NO: 3 (identical to the laminin polypeptide of instant SEQ ID NO: 1) and vitamin E as an antioxidant, wherein the composition-of-matter is in the form of hydrogel; and using such composition for treating nerve injury, such as CNS lesions in a subject in need thereof. Both Wang et al and Kabu et al teach hydrogel comprising hyaluronic acid and laminin for treating SCI. Furthermore, Kabu et al explicilty teach the beneficial effect of vitamin E in an SCI model. In addition, Eisenbach-Schwartz et al, throughout the patent, teach copolymer 1 for treating nerve injury of either PNS or central nervous system (CNS), such as SCI. Therefore, in view of the combined teachings of Rochkind et al, Wang et al, Kabu et al and Eisenbach-Schwartz et al, it would have been obvious to one of ordinary skilled in the art, and/or one of ordinary skilled in the art would be motivated to develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI. And, the MPEP states: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…” (see MPEP § 2144.06). Furthermore, in the instant case, other than statements/arguments, Applicant fails to provide any data and/or evidence to indicate that a composition comprising hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1 in the form of hydrogel developed from the combined teachings of Rochkind et al, Wang et al, Kabu et al and Eisenbach-Schwartz et al would not be able to treat SCI.
Second, with regards to the cited Coumans et al reference, as stated in the previous office action, the Examiner understands that the agents used in Coumans et al are not the same as instant claimed composition. However, in the instant case, as stated in Section 12 above, Coumans et al explicilty teach the benefits/advantages of deferred treatment of SCI. Coumans et al further explicilty teach environmental factors play a role in restricting axonal growth within a mature CNS environment, and the environment at the injury site may become more favorable for axonal growth over time after injury compared with the acutely injured spinal cord; and there may be differences in the ability of neurons themselves to mount a regenerative response. Therefore, in the instant case, in view of the teachings of Coumans et al as a whole, one of ordinary skilled in the art would understand and reasonably expect the benefits/advantages of deferred treatment of SCI in Coumans et al are not limited to the particular agents tested in Coumans et al.
Third, with regards to Applicant’s arguments about the number of references cited in instant rejection, the Examiner would like to point out that as stated in MPEP: “Reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention…” (see MPEP § 2145 V).
Taken all these together, in the instant case, in view of the combined teachings of the cited prior art references as set forth in Section 12 above, one of ordinary skilled in the art would be motivated to develop the method recited in instant claims 1-3, 8, 11, 12, 17 and 29; and a person of ordinary skilled in the art would have reasonable expectation of success to develop the method recited in instant claims 1-3, 8, 11, 12, 17 and 29. Furthermore, with regards to the expectation of success, the MPEP states: “Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. The Federal Circuit concluded that “[g]ood science and useful contributions do not necessarily result in patentability.” Id. at 1364, 83 USPQ2d at 1304.” (see MPEP § 2145).
Therefore, the rejection is deemed proper and is hereby maintained.
Obviousness Double Patenting
15. 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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
16. (Revised due to Applicant’s amendment to the claim) Claims 1-3, 8, 11, 12, 17 and 29 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11, 17 and 22 of US patent 8242076 B2 in view of Rochkind et al (US 2011/0104225 A1, filed with IDS), Wang et al (Interface Focus, 2012, 2, pages 278-291, filed with IDS), Kabu et al (Journal of Controlled Release, 2015, 219, pages 141-154, filed with IDS), Eisenbach-Schwartz et al (WO 2006/057003 A2, filed with IDS) and Coumans et al (The Journal of Neuroscience, 2001, 21, pages 9334-9344, cited and enclosed in the previous office actions).
17. Instant claim 1-3, 8, 11, 12, 17 and 29 are drawn to a method of deferred treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting at least 1 week after onset or diagnosis of the nerve injury in the subject a composition comprising hyaluronic acid, laminin polypeptide, vitamin E, and copolymer 1 at or near the nerve injury of the subject, thereby treating the nerve injury in the subject.
18. Claims 1-11, 17 and 22 of US patent 8242076 B2 are drawn to a polypeptide comprising the amino acid sequence set forth by SEQ ID NO: 3; a composition-of-matter comprising a polysaccharide and such polypeptide; a composition-of-matter comprising hyaluronic acid, a laminin polypeptide, set forth in SEQ ID NO: 3, and an antioxidant; a composition-of-matter comprising hyaluronic acid, superoxide dismutase (SOD) and such polypeptide; a matrix comprising the composition-of-matter claim 2; a hydrogel comprising the composition-of-matter of claim 2; a method of treating a subject having a pathology characterized by diseased, damaged or loss of tissue, the method comprising implanting the hydrogel of claim 11 at or near the diseased, damaged or loss tissue of the subject, thereby inducing the formation of the tissue and treating the subject; and a method of treating a subject having a pathology characterized by diseased, damaged or loss of tissue, the method comprising implanting the matrix of claim 10 at or near the diseased, damaged or loss tissue of the subject, thereby inducing the formation of the tissue and treating the subject.
The polypeptide of SEQ ID NO: 3 recited in claims of US patent 8242076 B2 is identical to the laminin polypeptide of instant SEQ ID NO: 1.
And in view of the combined teachings of claims 1-11, 17 and 22 of US patent 8242076 B2, it would have been obvious to one of ordinary skilled in the art to develop a method of treatment of tissue injury in a subject in need thereof, wherein the method comprises implanting a composition comprising polypeptide of SEQ ID NO: 3 (identical to the laminin polypeptide of instant SEQ ID NO: 1), hyaluronic acid and an antioxidant near the injured tissue, and wherein the composition is in the form of hydrogel.
19. The difference between instant claims 1-3, 8, 11, 12, 17 and 29 and the method developed from the combined teachings of claims 1-11, 17 and 22 of US patent 8242076 B2 above is that the method developed from the combined teachings of claims 1-11, 17 and 22 of US patent 8242076 B2 above does not teach copolymer 1, the deferred treatment and the nerve injury recited in instant claim 1; and the limitations of instant claims 2, 3, 8, 11, and 12.
However, Rochkind et al, throughout the patent, teach a composition-of-matter comprising hyaluronic acid, a laminin polypeptide and an antioxidant, wherein the composition-of-matter is in the form of hydrogel, wherein the laminin polypeptide is SEQ ID NO: 3 consisting of the amino acid sequence KSIKVAVRSYIGSRCV (identical to the laminin polypeptide of instant SEQ ID NO: 1), and wherein the composition-of-matter induces neuronal cell differentiation of primary fetal rat brain cells derived from cerebral hemispheres of rat; and a method of treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting the composition-of-matter at or near the nerve injury of the subject, wherein the nerve injury is caused by trauma, and wherein the nerve injury can be CNS lesions, for example, Abstract; Figures 2 and 3; page 1, paragraphs [0006], [0008], [0011], [0014], [0015], [0019] and [0020]; page 2, paragraphs [0032], [0041], [0043], [0045] and [0046]; page 7, paragraph [0102]; page 8, paragraphs [0112] and [0113]; page 11, Example 2, in particular paragraphs [0151], [0162] and [0163]; and claims 5, 7-11, 13 and 24. Rochkind et al further teach the antioxidant in the composition-of-matter can be vitamin E, for example, page 6, paragraph [0069]. Therefore, in view of the teaching of Rochkind et al as a whole, one of ordinary skilled in the art would understand and reasonably expect a composition-of-matter comprising hyaluronic acid, a laminin polypeptide of SEQ ID NO: 3 (identical to the laminin polypeptide of instant SEQ ID NO: 1) and vitamin E as an antioxidant, wherein the composition-of-matter is in the form of hydrogel; and using such composition for treating nerve injury, such as CNS lesions in a subject in need thereof.
In addition, Wang et al, throughout the literature, teach hydrogel comprising hyaluronic acid (HA) and laminin improves neural regeneration, and can be used for treating damage to CNS, such as spinal cord injury (SCI), for example, Abstract; page 278, left column, the 1st paragraph in Section “1. INTRODUCTION”; page 280, right column, the 1st paragraph in Section “2.1.3. Modification of engineered extracellular matrix components”; pages 282-283, Section “3.3. Modification of hyaluronic acid hydrogels”; and page 284, Section “3.4.2. Delivery of neurotrophic factors using hyaluronic acid-based scaffolds”.
Furthermore, Kabu et al, throughout the literature, teach current treatments used for SCI can be categorized mainly as neuroprotective or neuroregenerative in nature; early interventions following primary injury are aimed at preventing cascades of secondary degeneration, particularly drug and neuroprotective therapies, whereas at a chronic stage, it is primarily regenerative therapy such as cell-based therapies, tissue engineering, either through remyelination and/or axonal sprouting to establish neuronal connectivity and achieve functional recovery; and the timing of therapeutic interventions as one of the important factors contributing to success of treating SCI, for example, Abstract; and pages142-143, Figure 1 and Section “1.2. Therapeutic and regenerative strategies for treatment of spinal cord injury”. Kabu et al further teach high doses of antioxidants, vitamins C and E (100 mg/kg/day), in an SCI model have shown to lessen the inflammatory response; and the role of SOD in neuroprotection against oxidative stress in SCI, for example, pages 144-145, Sections “1.4.6. Targeting oxidative stress” and “1.4.6.1. Antioxidant enzymes”. Kabu et al also teach hydrogel comprising hyaluronic acid and laminin for treating SCI, for example, page 148, Section “3.1. Hydrogels for tissue engineering”. Therefore, in view of the combined teachings of Rochkind et al, Wang et al and Kabu et al, it would have been obvious to one of ordinary skilled in the art to modify the method developed from the combined teachings of claims 1-11, 17 and 22 of US patent 8242076 B2 and develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, and vitamin E as an antioxidant; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI.
And, Eisenbach-Schwartz et al, throughout the patent, teach copolymer 1 for treating nerve injury of either PNS or central nervous system (CNS), such as SCI, for example, Abstract; page 1, lines 6-10; page 36, lines 3-8; and page 37, lines 1-10. Therefore, in view of the combined teachings of Rochkind et al, Wang et al, Kabu et al and Eisenbach-Schwartz et al, it would have been obvious to one of ordinary skilled in the art to modify the method developed from the combined teachings of claims 1-11, 17 and 22 of US patent 8242076 B2 and develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, vitamin E as an antioxidant, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI. And, the MPEP states: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…” (see MPEP § 2144.06).
In addition, Coumans et al, throughout the literature, teach that in comparison to applied acutely, deferred treatment of SCI with neurotrophins (applied 2-4 weeks after the onset of SCI) dramatically increases regeneration from supraspinal pathways and recovery of motor function, for example, Abstract; page 9335, left column, the 2nd paragraph; page 9336, right column, the 2nd, 3rd and 4th paragraphs; and page 9343, the paragraph bridging the left and right columns. Coumans et al further teach environmental factors play a role in restricting axonal growth within a mature CNS environment, and the environment at the injury site may become more favorable for axonal growth over time after injury compared with the acutely injured spinal cord; and there may be differences in the ability of neurons themselves to mount a regenerative response, for example, page 9342, right column, the 2nd and 3rd paragraphs.
Therefore, in view of the combined teachings of Rochkind et al, Wang et al, Kabu et al, Eisenbach-Schwartz et al and Coumans et al, it would have been obvious to one of ordinary skilled in the art to modify the method developed from the combined teachings of claims 1-11, 17 and 22 of US patent 8242076 B2 above and develop the method recited in instant claims 1-3, 8, 11, 12, 17 and 29.
20. (Revised due to Applicant’s amendment to the claim) Claims 1-3, 8, 11, 12, 17 and 29 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of US patent 10729815 B2 in view of Coumans et al (The Journal of Neuroscience, 2001, 21, pages 9334-9344, cited and enclosed in the previous office actions).
21. Instant claim 1-3, 8, 11, 12, 17 and 29 are drawn to a method of deferred treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting at least 1 week after onset or diagnosis of the nerve injury in the subject a composition comprising hyaluronic acid, laminin polypeptide, vitamin E, and copolymer 1 at or near the nerve injury of the subject, thereby treating the nerve injury in the subject.
22. Claims 1-17 of US patent 10729815 B2 are drawn to a composition comprising a hyaluronic acid, a laminin polypeptide, an antioxidant and Copaxone; a matrix comprising such composition; a hydrogel comprising such composition; a method of inducing formation or regeneration of a neuronal tissue in a subject in need thereof, the method comprising implanting such composition in the subject, thereby inducing the formation or regeneration of the neuronal tissue in the subject; a method of treating nerve injury in a subject in need thereof, the method comprising implanting such composition at or near the nerve injury of the subject, thereby treating the nerve injury in the subject; and a method of preventing or treating neurogenic shock following nerve injury in a subject in need thereof, the method comprising implanting such composition at or near the nerve injury of the subject, thereby preventing or treating the neurogenic shock in the subject.
The polypeptide of SEQ ID NO: 1 recited in claims of US patent 10729815 B2 is identical to the laminin polypeptide of instant SEQ ID NO: 1; and Copaxone recited in claims of US patent 10729815 B2 is the tradename of copolymer 1.
And in view of the combined teachings of claims 1-17 of US patent 10729815 B2, it would have been obvious to one of ordinary skilled in the art to develop a method of treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting a composition comprising laminin polypeptide of instant SEQ ID NO: 1, hyaluronic acid, vitamin E as an antioxidant, and copolymer 1 at or near the nerve injury; wherein the composition is in the form of hydrogel, and wherein the nerve injury is part of CNS, such as SCI, TBI or TON.
23. The difference between instant claims 1-3, 8, 11, 12, 17 and 29 and the method developed from the combined teachings of claims 1-17 of US patent 10729815 B2 above is that the method developed from the combined teachings of claims 1- 17 of US patent 10729815 B2 above does not teach the deferred treatment recited in instant claim 1; and the limitations of instant claims 2 and 3.
However, Coumans et al, throughout the literature, teach that in comparison to applied acutely, deferred treatment of SCI with neurotrophins (applied 2-4 weeks after the onset of SCI) dramatically increases regeneration from supraspinal pathways and recovery of motor function, for example, Abstract; page 9335, left column, the 2nd paragraph; page 9336, right column, the 2nd, 3rd and 4th paragraphs; and page 9343, the paragraph bridging the left and right columns. Coumans et al further teach environmental factors play a role in restricting axonal growth within a mature CNS environment, and the environment at the injury site may become more favorable for axonal growth over time after injury compared with the acutely injured spinal cord; and there may be differences in the ability of neurons themselves to mount a regenerative response, for example, page 9342, right column, the 2nd and 3rd paragraphs.
Therefore, in view of the teachings of Coumans et al, it would have been obvious to one of ordinary skilled in the art to modify the method developed from the combined teachings of claims 1-17 of US patent 10729815 B2 above and develop the method recited in instant claims 1-3, 8, 11, 12, 17 and 29.
24. (Revised due to Applicant’s amendment to the claim) Claims 1-3, 8, 11, 12, 17 and 29 remain provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 4-6, 26, 41, 43, 46, 51 and 52 of co-pending Application No. 17617095 in view of Rochkind et al (US 2011/0104225 A1, filed with IDS), Wang et al (Interface Focus, 2012, 2, pages 278-291, filed with IDS), Kabu et al (Journal of Controlled Release, 2015, 219, pages 141-154, filed with IDS) and Coumans et al (The Journal of Neuroscience, 2001, 21, pages 9334-9344, cited and enclosed in the previous office actions).
25. Instant claim 1-3, 8, 11, 12, 17 and 29 are drawn to a method of deferred treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting at least 1 week after onset or diagnosis of the nerve injury in the subject a composition comprising hyaluronic acid, laminin polypeptide, vitamin E, and copolymer 1 at or near the nerve injury of the subject, thereby treating the nerve injury in the subject.
26. Claims 1, 4-6, 26, 41, 43, 46, 51 and 52 of co-pending Application No. 17617095 are drawn to a hydrogel comprising a hyaluronic acid, a laminin polypeptide, vitamin E and Copolymer 1 at a concentration range of 10 - 150 µg/ml, wherein the hydrogel is comprised in an implantable tube; a method of inducing formation or regeneration of a tissue in a subject in need thereof, the method comprising implanting the composition, the matrix or the hydrogel of claim 1 in the subject, thereby inducing the formation or regeneration of the tissue in the subject; a method of treating a pathology characterized by diseased, damaged or loss of tissue in a subject in need thereof, the method comprising implanting the composition of claim 1, thereby treating the pathology in the subject; a method of preventing or treating neurogenic shock following nerve injury in a subject in need thereof, the method comprising implanting the composition of claim 1, thereby preventing or treating the neurogenic shock in the subject; and a hydrogel comprising a hyaluronic acid, a laminin polypeptide, vitamin E at a concentration of 3mM, and Copolymer 1 at a concentration of 10 µg/ml, wherein the hydrogel is comprised in an implantable tube.
The laminin polypeptide of SEQ ID NO: 1 recited in claims of co-pending Application No. 17617095 is identical to the laminin polypeptide of instant SEQ ID NO: 1.
And in view of the combined teachings of claims 1, 4-6, 26, 41, 43, 46, 51 and 52 of co-pending Application No. 17617095, it would have been obvious to one of ordinary skilled in the art to develop a method of treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting a composition comprising laminin polypeptide of instant SEQ ID NO: 1, hyaluronic acid, vitamin E, and copolymer 1 at or near the nerve injury; and wherein the composition is in the form of hydrogel.
27. The difference between instant claims 1-3, 8, 11, 12, 17 and 29 and the method developed from the combined teachings of claims 1, 4-6, 26, 41, 43, 46, 51 and 52 of co-pending Application No. 17617095 above is that the method developed from the combined teachings of claims 1, 4-6, 26, 41, 43, 46, 51 and 52 of co-pending Application No. 17617095 above does not teach the deferred treatment recited in instant claim 1; and the limitations of instant claims 2, 3, 8, 11 and 12.
However, Rochkind et al, throughout the patent, teach a composition-of-matter comprising hyaluronic acid, a laminin polypeptide and an antioxidant, wherein the composition-of-matter is in the form of hydrogel, wherein the laminin polypeptide is SEQ ID NO: 3 consisting of the amino acid sequence KSIKVAVRSYIGSRCV (identical to the laminin polypeptide of instant SEQ ID NO: 1), and wherein the composition-of-matter induces neuronal cell differentiation of primary fetal rat brain cells derived from cerebral hemispheres of rat; and a method of treatment of nerve injury in a subject in need thereof, wherein the method comprises implanting the composition-of-matter at or near the nerve injury of the subject, wherein the nerve injury is caused by trauma, and wherein the nerve injury can be CNS lesions, for example, Abstract; Figures 2 and 3; page 1, paragraphs [0006], [0008], [0011], [0014], [0015], [0019] and [0020]; page 2, paragraphs [0032], [0041], [0043], [0045] and [0046]; page 7, paragraph [0102]; page 8, paragraphs [0112] and [0113]; page 11, Example 2, in particular paragraphs [0151], [0162] and [0163]; and claims 5, 7-11, 13 and 24.
Furthermore, Wang et al, throughout the literature, teach hydrogel comprising hyaluronic acid (HA) and laminin improves neural regeneration, and can be used for treating damage to CNS, such as spinal cord injury (SCI), for example, Abstract; page 278, left column, the 1st paragraph in Section “1. INTRODUCTION”; page 280, right column, the 1st paragraph in Section “2.1.3. Modification of engineered extracellular matrix components”; pages 282-283, Section “3.3. Modification of hyaluronic acid hydrogels”; and page 284, Section “3.4.2. Delivery of neurotrophic factors using hyaluronic acid-based scaffolds”.
In addition, Kabu et al, throughout the literature, teach current treatments used for SCI can be categorized mainly as neuroprotective or neuroregenerative in nature; early interventions following primary injury are aimed at preventing cascades of secondary degeneration, particularly drug and neuroprotective therapies, whereas at a chronic stage, it is primarily regenerative therapy such as cell-based therapies, tissue engineering, either through remyelination and/or axonal sprouting to establish neuronal connectivity and achieve functional recovery; and the timing of therapeutic interventions as one of the important factors contributing to success of treating SCI, for example, Abstract; and pages142-143, Figure 1 and Section “1.2. Therapeutic and regenerative strategies for treatment of spinal cord injury”. Kabu et al further teach high doses of antioxidants, vitamins C and E (100 mg/kg/day), in an SCI model have shown to lessen the inflammatory response; and the role of SOD in neuroprotection against oxidative stress in SCI, for example, pages 144-145, Sections “1.4.6. Targeting oxidative stress” and “1.4.6.1. Antioxidant enzymes”. Kabu et al also teach hydrogel comprising hyaluronic acid and laminin for treating SCI, for example, page 148, Section “3.1. Hydrogels for tissue engineering”. Therefore, in view of the combined teachings of Rochkind et al, Wang et al and Kabu et al, it would have been obvious to one of ordinary skilled in the art to modify the method developed from the combined teachings of claims 1, 4-10, 23, 24, 26, 27, 29, 31-33, 41, 43 and 46 of co-pending Application No. 17617095 above and develop a method of treatment of SCI in a subject in need thereof, wherein the method comprises implanting a composition at or near the nerve injury of the subject; wherein the composition comprises hyaluronic acid, laminin polypeptide of instant SEQ ID NO: 1, an antioxidant being either SOD comprising the amino acid sequence of instant SEQ ID NO: 4 or vitamin E, and copolymer 1; wherein the composition is in the form of hydrogel; wherein the SCI is caused by trauma; and wherein the composition is implanted at the chronic stage of SCI.
And, Coumans et al, throughout the literature, teach that in comparison to applied acutely, deferred treatment of SCI with neurotrophins (applied 2-4 weeks after the onset of SCI) dramatically increases regeneration from supraspinal pathways and recovery of motor function, for example, Abstract; page 9335, left column, the 2nd paragraph; page 9336, right column, the 2nd, 3rd and 4th paragraphs; and page 9343, the paragraph bridging the left and right columns. Coumans et al further teach environmental factors play a role in restricting axonal growth within a mature CNS environment, and the environment at the injury site may become more favorable for axonal growth over time after injury compared with the acutely injured spinal cord; and there may be differences in the ability of neurons themselves to mount a regenerative response, for example, page 9342, right column, the 2nd and 3rd paragraphs.
Thus, in view of the combined teachings of Rochkind et al, Wang et al, Kabu et al and Coumans et al, it would have been obvious to one of ordinary skilled in the art to modify the method developed from the combined teachings of claims 1, 4-6, 26, 41, 43, 46, 51 and 52 of co-pending Application No. 17617095 above and develop the method recited in instant claims 1-3, 8, 11, 12, 17 and 29.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Response to Applicant's Arguments
28. Applicant argues that these ODP rejections are exactly the same as the previously discussed 103 rejection based on the same arts.
29. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant’s arguments about these ODP rejections, Applicant’s arguments about the 103 rejection have been addressed in Section 14 above.
Taken all these together, until a proper terminal disclaimer is filed and approved by the Office, these double patenting rejections are hereby maintained.
New Objections
30. Claim 2 is objected to for the following minor informality: Claim 2 recites “The method of claim 1, wherein said i composition is implanted…”. There appears to be an extra “i” in this recitation. Applicant is required to correct this error.
Conclusion
All claims are drawn to the same invention claimed in the application prior to the entry of the submission under 37 CFR 1.114 and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LI N KOMATSU whose telephone number is (571)270-3534. The examiner can normally be reached Mon-Fri 8am-4pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached on 5712707430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LI N KOMATSU/ Primary Examiner, Art Unit 1658