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 .
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 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.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Jul. 15, 2025 has been entered. All arguments have been fully considered.
Status of the Claims
Claims 1-8 currently pending.
Claim 1 is amended.
New claim 8 has been added.
Claims 1-8 have been considered on the merits.
Claim Rejections - 35 USC § 103
The claim rejections under 35 USC § 103 are withdrawn due to amendment. New claim rejections under 35 USC § 103 have been added to address the claim amendments.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Stephan (WO 2014/110591 A1) (ref. of record) in view of Shabalovskaya et al. (Acta Biomaterialia, 2008) (ref. of record), Shabalovskaya et al. (Journal of Materials Research, 2004) (“Shabalovskaya 2004”) and Wang et al. (ACS Applied Materials & Interfaces, 2015) (ref. of record).
With respect to claim 1, Stephan teaches a scaffold containing lymphocytes and at least one lymphocyte-activating moiety and where the lymphocytes are genetically-modified (genetically reprogrammed) (abstract, 0002, 0010, 0070, 00111 and 00143). With respect to claim 1, Stephan teaches the scaffold comprises fibrin (0069). With respect to claim 1, Stephan teaches the scaffold can be coated with a lymphocyte-activating moiety (0070) and exemplary lymphocyte-activation moieties include CD3, CD28 and CD137 antibodies (0010 and 0077).
Although, Stephen teaches the method where the porous scaffold contains at least 7 x106 lymphocytes (0007 and 00141), Stephen is silent with respect to the density of the lymphocytes and does not teach the claimed density of at least 7 x106 genetically-reprogrammed lymphocytes per cm2 as recited in claim 1. Even though Steven does not teach the density of the cells in the scaffold, one of ordinary skill in the art would recognize that the lymphocyte density in the scaffold is a result effective variable and that the lymphocyte density in the scaffold would be matter of routine optimization as evidenced by Stephen. Stephen teaches that the depending on the stage, size, severity of the tumor, the composition can be provided with different therapeutic strengths which can be manipulated by altering the size of the composition, volume of the composition, the number of lymphocytes embedded in the composition, the number of lymphocyte-activating moieties within a composition, the presence or amount of immune stimulants within the composition and other factors (00128). Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) -MPEP § 2144.05.
With respect to claim 2, Stephan teaches the scaffold can be coated with a lymphocyte-activating moiety where the lymphocyte-activation moieties include CD3, CD28 and CD137 antibodies (0006, 0010, and 0070). Further with respect to claim 2, Stephan teaches the lymphocytes are T-cells and can be genetically modified (0007 and 00110-00114).
With respect to claim 3, Stephan teaches the scaffold can be coated with a lymphocyte-activating moiety where the lymphocyte-activation moiety includes CD137 antibodies (0006, 0010, and 0070) and the scaffold further containing an immune stimulant which is interleukin 15 (0011). Further with respect to claim 3, Stephan teaches the lymphocytes are natural killer cells and can be genetically modified (0007, 0099 and 00109-00114).
With respect to claim 4, Stephan teaches the scaffold can be coated with a lymphocyte-activating moiety where the lymphocyte-activation moiety includes CD137 antibodies (0006, 0010, and 0070). Further with respect to claim 4, Stephan teaches the lymphocytes include T cells and natural killer cells and can be genetically modified (0099 and 00109-00114).
With respect to claim 8, Stephen teaches the lymphocyte-activating moiety is covalently coupled to the collagen (0069-0071).
Stephan does not teach the scaffold comprising thin film nitinol micromesh as recited in claim 1. However, Shabalovskaya teaches a scaffold with a coating of a thin film Nitinol forming a mesh which contains cells and that NiTi is compatible with lymphocytes such substrates (abstract, pg. 452 Col. 2 para. 2, pg. 454 Col. 2 para. 2, and pg. 462 para. 1). In addition, Shabalovskaya teaches that Nitinol is commonly used medical implants (abstract). In further support, Shabalovskaya 2004 teaches culturing lymphocytes on Nitinol surfaces (abstract). Shabalovskaya 2004 teaches that Nitinol has remarkable biocompatibility in vivo (pg. 1 last para.). Additionally, Shabalovskaya 2004 teaches that lymphocytes proliferated on NiTi substrates (pg. 7 para. 4 to pg. 8 para. 3, pg. 10 last para., pg. 11 para. 2). In additional support, Wang reports that “Nitinol is widely fabricated as stents for the palliation treatment of many kinds of cancer” (abstract) and that Nitinol has a good biocompatibility and unique shape memory effects (pg. 7843 para. 1).
Accordingly, at effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the scaffold of Stephan to include a thin film Nitinol micromesh for its biocompatible as taught by Shabalovskaya and Wang, and is unique shape memory effects as taught by Wang and its known ability as a substrate for lymphocytes as taught by Shabalovskaya 2004. Furthermore, it would have been obvious to one of ordinary skill in the art to modify the scaffold of Stephan to include a thin film Nitinol micromesh, since scaffolds containing such materials were known to carry lymphocytes and to be used in cancer treatments as taught by Shabalovskaya, Shabalovskaya 2004, and Wang. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in modifying the scaffold of Stephan to include a thin film Nitinol micromesh, since scaffolds containing such materials were known to carry lymphocytes, to be used in cancer treatments and to be biocompatible as taught by Shabalovskaya, Shabalovskaya 2004, and Wang.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 5-7 are rejected under 35 U.S.C. 103(a) as being unpatentable over Stephan in view of Shabalovskaya, Shabalovskaya 2004 and Wang (as applied to claims 1-4 and 8), and further in view of Vernejoul et al. (US 2017/0340658 A1, priority to Dec. 16, 2014) (ref. of record).
The teachings of Stephan, Shabalovskaya, Shabalovskaya 2004, and Wang can be found in the previous rejection above.
Stephan does not teach the scaffold further comprising a stimulator of interferon genes (STING) agonist as recited in claim 5, any of the STING agonist listed in claim 6, or that the STING agonist is c-diGMP as recited in claim 7. However, Vernejoul teaches a composition for the treatment of cancer containing an STING agonist (abstract, 0018 and 0028) and where the STING agonists is c-diGMP, c-diAMP, c-CAMP, c-AIMP, (3’,2’)c-AIMP, OR (2’,2’)c-AIMP, (2’,3’)c-AIMP, c-AIMP(S), c-(dAMP-dIMP), c-(dAMP-2’FdIMP), c-(2’FdAMP-2’FdIMP), (2’,3’)c-(AMP-2’FdIMP), c-[2’FdAMP(S)-2’FdIMP(S)] , and c-[2’FdAMP(S)-2’FdIMP(S)](POM)2 (Table 1, 0011-0014 and 0071-0073). In further support, Stephan teaches the scaffold can contain immune stimulants (0011). Vernejoul teaches STING agonist have been shown to activate the immune system (0011-0012). Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to include a STING agonist in the scaffold of Stephan for the benefit of further treating cancer. It would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to combine the instant ingredients for their known benefit, as disclosed by the cited references above, since each is well known in the art for their claimed purpose in treating cancer. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in modifying the scaffold of Stephan to include a STING agonist including those listed in claim 6, since STING agonist were well known for their use in treating cancer. The idea for combining them flows logically from their having been used individually in the prior art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Jul. 15, 2025 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that none of Stephan, Shabalovskaya and Wang teach or suggest the recited cell density (Remarks pg. 4 para. 5-6). The Applicant’s amendments limiting claim 1 to include the density of the lymphocytes of at least 7 x 106 cells per cm2 within the scaffold necessitated a new rejection and withdrawal of the previous rejection. Applicant’s arguments are drawn to Stephan, Shabalovskaya and Wang failing to teach this new limitation. However, this new limitation is addressed in the new rejection.
Applicant argues that Shabalovskaya does not teach that lymphocytes can be cultured on a TFN mesh and instead Shabalovskaya teaches a nitinol stent for a disease blood vessel where platelets or lymphocytes bind which is different from culture (Remarks pg. 4 last para.). This argument was not found to be persuasive, since the claims are not directed to culturing lymphocytes on a TFN mesh but to a scaffold containing a TFN mesh and lymphocytes. After an updated search, a new reference, Shabalovskaya 2004, was found which teaches lymphocytes disposed on a Nitinol scaffold and that lymphocytes on a Nitinol scaffold proliferate as explained in the current rejections under 35 U.S.C. § 103. It has been noted in the new rejection that Shabalovskaya teaches compatibility of NiTi (Nitinol) substrates with lymphocytes.
Applicant argues one of ordinary skill in the art would not have been motivated to use TFN in the scaffold taught by Stephan based on the teachings of Shabalovskaya, since Stephan is directed to using a Nitinol scaffold in treating cancer or tumors and of Shabalovskaya is directed to stents (Remarks pg. 5 para. 1). However, this argument was not found to be persuasive, since both are directed to compositions where cells are embedded in a biocompatible scaffold for potential therapeutic purposes (see abstract of Shabalovskaya and Stephen).
Applicant argues that Wang actually teaches that the films of nickel hydroxide and nickel-titanium layered double hydroxide inhibit the growth of cancer cells and not the Nitinol which the films coat (Remarks pg. 5 para. 2). This argument was found to be persuasive, and Wang is no longer being relied upon for this teaching.
Applicant argues at that one of ordinary skill in the art would not have been motivated to include Nitinol the scaffold of Stephan, since Wang teaches Nitinol stents do not have tumor inhibition effects and it is the films that inhibit cancer cells and not normal cells (Remarks pg. 5 para. 3-4). This argument was found to be partially persuasive, in that Wang teaches it is the films coating the Nitinol which inhibit cancer cells and not normal cells. However, Wang also teaches the benefits of Nitinol as a scaffold for treating cancer include good biocompatibility, unique shape memory effects and that it has been used in stents for the palliation treatment of many kinds of cancer (abstract and pg. 7843 para. 1).
Applicant argues that Vernejoul does not remedy this deficiency (Remarks pg. 6 para. 1). However, this argument was not found to be persuasive, since the arguments with respect to the rejections over Stephan, Shabalovskaya and Wang were not found to be persuasive as explained above.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632