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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/5/2024 has been entered.
Election/Restrictions
Applicant’s election without traverse of the species: treating uveitis; a nucleic acid; polypeptide comprising 1-182 of IL-34; AAV7m8 vector; constitutive promotor, posterior uveitis, autoimmune disorder, an immunomodulatory agent and sub-retinal administration in the reply filed on 12/8/2023 is acknowledged. It is notes that while applicant responded to species election of groups I and J, bacterial infection and retinitis pigmentosa, that these are subspecies of species groups that were not elected and therefore, not under consideration and withdrawn.
Claims 12-14, 19-20, 22-29, 35-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/8/2023.
Claims 1-2, 6-7, 10-11, 15-18, 31-34, 37 and 39 are under consideration in the instant Office Action.
Information Disclosure Statement
The information disclosure statements filed 12/5/2024 fail to fully comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because no copies for non-patent literature cited in the IDS were provided and the citations have therefore been lined through. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a). All references listed in the IDS that are not provided are lined through and not considered.
Withdrawn Rejections
The rejection of claim 3 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot since the claim has been cancelled.
Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 6-7, 15-18, 31-33, 37 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Guillonneau et al., US 2017/0202921 (IDS, 8/19/2020) in view of Amador-Patarroyo et al., 2013 (2/14/2024 PTO-892).
Guillonneau teaches the use of isolated interleukin -34 (IL-34) and a method of treating autoimmune diseases (see paragraphs 1 and 108 and claims 1, 5-6 and 9). Guillonneau teaches IL-34 polypeptide or a polynucleotide encoding thereof for the treatment of autoimmune diseases and allergies in patients in need thereof (see paragraph 11) as in instant claim 1-2 and 18. Guillonneau teaches SEQ ID NO: 1 for the human IL-34 as a 242 amino acid sequence (see paragraph 59 and claims 1, 5-6 and 9) which is the same as instantly SEQ ID NO:1 of instant claims 1 and 6-7 since it comprises the required 1-182 amino acids of the instant SEQ ID NO:1. Guillonneau teaches the combination of immunosuppressive drugs in combination with IL-34 polypeptide or a polynucleotide encoding thereof (see paragraph 12) as in instant claim 32. Guillonneau teaches the immunosuppressive drugs include glucocorticoids and calcineurin inhibitors (see paragraph 133 and claim 7) as in instant claims 32-33. Guillonneau teaches that the patient population is human (see paragraph 29) as in instant claim 31. Guillonneau teaches that IL-34 promotes the proliferation, survival and differentiation of macrophages (see paragraph 59). Microglia cells are the macrophages of the central nervous system (see paragraph 266) and therefore, meets the requirements of instant claims 2 and 37. Guillonneau teaches using vectors with adeno-associated virus (AAV) such as AAV8 and promoters to express the IL-34 nucleotide to produce the IL-34 protein since they are double stranded DNA viruses that have already been approved for human use in gene therapy (see paragraphs 113, 116, 118, 120, 207, 224 and 267).
Guillonneau teaches that the autoimmune diseases they can treat with the IL-34 include rheumatoid arthritis and systemic lupus erythematosus (see paragraph 54) but does not specifically teach treating uveitis.
Amador-Patarroyo teaches that autoimmune uveitis is an eye inflammation that presents with many autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosus (see page 1). Amador-Patarroyo teaches that uveitis include anterior and posterior uveitis and also included iritis, choroiditis, retinochoroiditis and chorioretinitis (see page 1) as in instant claims 15-18 and 39. Amador-Patarroyo teaches treating uveitis with calcineurin inhibitors (see page 9) as in instant claims 32-33 but fails to teach using IL-34 a treatment.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Guillonneau and Amador-Patarroyo. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Amador-Patarroyo teaches that autoimmune uveitis is an inflammatory disease that is found within the patient populations with rheumatoid arthritis and systemic lupus erythematosus. Therefore, one of ordinary skill in the art would look the teaching of Guillonneau which teaches that the autoimmune diseases are treated with the IL-34 include rheumatoid arthritis and systemic lupus erythematosus. One of ordinary skill in the art would be motivated to administer the IL-34 treat to the eye of uveitis patients since uveitis, rheumatoid arthritis and systemic lupus erythematosus are diseases that overlap. It would be reasonable to expect the treatment of IL-34 be capable of treating uveitis since it has already been shown to be successful in treating other inflammatory diseases like rheumatoid arthritis and systemic lupus erythematosus. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claims 1-2, 6-7, 10-11, 15-18, 31-34, 37 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Guillonneau et al., US 2017/0202921 (IDS, 8/19/2020) and Amador-Patarroyo et al., 2013 (2/14/2024 PTO-892), and further in view of Chalberg et al., US2015/0259395 (IDS, 8/19/20220).
Neither Guillonneau nor Amador-Patarroyo teaches the AAV7m8 vector, constitutive promotor or subretinal administration as required in instant claims 10-11 and 34.
Chalberg teaches polynucleotide expression vectors for the expression of genes in the retina. Chalberg teaches that the promising approach of treating ophthalmic diseases is to deliver the therapeutic agents to the eye with gene therapy vectors such as AAV (See paragraph 6). Chalberg teaches administering the pharmaceutical composition to the eye via the subretinal space of the mammalian eye (see paragraphs 6, 21, 195-196) as instant claim 34. Chalberg teaches the use of AAV2-7m8 to transduce genes into the photoreceptors in the retina. Chalberg teaches that the 7m8 is better than the wildtype-AAV2 in transducing these cells (see paragraph 243) and in instant claim 10. Chalberg teaches that one may use constitutive promoters so that they are continually active (see paragraph 56) as in instant claim 11. Chalberg does no teach treating uveitis or the use of IL-34.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Guillonneau, Amador-Patarroyo and Chalberg. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because the treatment for uveitis encompasses the treatment of the retina and one of ordinary skill in the art would want to administer the treatment directly to the eye and Chalberg teaches the promising approach of treating ophthalmic diseases is to deliver the therapeutic agents to the eye with gene therapy vectors. One of ordinary skill would want to administer the IL-34 via the AAV7m8 vector since it is specific to the retina, administer it subretinally to get it as closely delivered to the target region as possible and use a constitutive promoter in the vector with IL-34 so that the vector is continually active in producing the therapeutic IL-34 and protect the retina from inflammation caused by uveitis. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Response to Amendment
The declaration under 37 CFR 1.132 filed 12/5/2024 is insufficient to overcome the rejection of claims 1-2, 6-7, 10-11, 15-18, 31-34, 37 and 39 over Guillonneau et al., US 2017/0202921 (IDS, 8/19/2020) and Amador-Patarroyo et al., 2013 (2/14/2024 PTO-892), view of Chalberg et al., US2015/0259395 (IDS, 8/19/20220) as set forth in the last Office action because: The declaration argues that there is no evidence in the main reference, Guillonneau, to treat uveitis and that autoimmunity and alloimmunity are different systems and that one of ordinary art could not predict anything in either system since there are not the same. This is not found persuasive since both autoimmunity and alloimmunity are pathways in the immune system and one of ordinary skill in the art would be capable of deducing teachings that may be used in both system from the teachings in the prior that are in the same field of endeavor. While the immune response is complex, it is not wildly unpredictable as set forth in the declaration and one of ordinary skill in the art is capable of analyzing the prior art and gain insight on how to produce potential treatments with a reasonable expectation of success. The arguments are further addressed below.
The declaration is not found persuasive for the reasons set forth below and as already discussed above.
Response to Arguments
Applicant's arguments filed 12/5/2024 have been fully considered but they are not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant argues that neither references, Guillonneau or Amador-Patarroyo, teach treating uveitis with IL-34. This is not found persuasive because the combination of references is what provides the motivation to use IL-34 to treat IL-34.
Applicant also argues that treatment to the eye is unpredictable due to the blood retinal barrier (BRB) inferring the treatments cannot cross the BRB to reach the retina. This is not found persuasive for a few reasons. The first is that it depends what type of uveitis is being considered. If one is contemplating anterior uveitis which affects the iris, then the BRB is not a consideration. If one is discussing posterior uveitis that affects retina and choroid in the back of the eye, then one of ordinary skill in the art would be administering the treatment via intravitreal injections if one has a direct access to the retina. Further, the Chalberg reference already teaches the way to overcome the BRB issue. Chalberg teaches administering the pharmaceutical composition to the eye via the subretinal space of the mammalian eye (see paragraphs 6, 21, 195-196). This shows that there are well-known routes of administration for treatment of the eye so that one does not have to deal with BRB. Therefore, this argument is not found persuasive.
Applicant further argues that treatment of autoimmune disease is generally unpredictable and points to rapamycin being used to treat other autoimmune conditions and that low doses of rapamycin exacerbates autoimmune uveitis. This is not on point since rapamycin is not the claimed treatment for the instant claims. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also >Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005). Applicant is reminded that the test for obviousness is not whether the features of the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 413, 425, 208 USPQ 871, 881 (CCPA 1981). Applicant’s arguments do not show how the combined teachings of the cited references and the knowledge/skills contained therein cannot render the rejected claims obvious.
Applicant continues to argue that Guillonneau teaches the use of isolated interleukin-34 to treat transplant rejection and alloimmune responses but that there is no evidence that it would treat autoimmune disease since the there is no preclinical evidence that the Il-34 would treat uveitis in the reference. This is not found persuasive. Guillonneau specifically teaches: “[0029] By “patient in need thereof is meant an individual suffering from or susceptible of suffering from transplant rejection, an autoimmune diseases, alloimmune responses or allergies to be treated. The individuals to be treated in the frame of the invention are mammals, preferably human beings.”
This speaks to the fact the prior art has a reasonable expectation of success in applying the disclosed treatment to subject with autoimmune disease. As already discussed above, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. 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. “Good science and useful contributions do not necessarily result in patentability.” PharmaStem Therapeutics, Inc. v. Viacell, Inc., 491 F.3d 1342 (Fed. Cir. 2007). It is also further pointed out that the instant claims are not limited to retinal degeneration but rather the species that was selected is uveitis.
Applicants’ stating that there is no evidence of predictability and their declaration to the same essence, is not found persuasive. Applicant’s argument that there are no working examples, specifically preclinical animal models, in the Guillonneau reference over use of IL-34 to treat uveitis, is their evidence that there is no reasonable expectation of success or motivating to use the claimed treatment in the patient population with uveitis. This is not found persuasive.
See MPEP § 2164.02 which states “An applicant need not have actually reduced the invention to practice prior to filing. In Gould v. Quigg, 822 F.2d 1074, 1078, 3 USPQ 2d 1302, 1304 (Fed. Cir. 1987), as of Gould’s filing date, no person had built a light amplifier or measured a population inversion in a gas discharge. The court held that "The mere fact that something has not previously been done clearly is not, in itself, a sufficient basis for rejecting all applications purporting to disclose how to do it." 822 F.2d at 1078, 3 USPQ2d at 1304 (quoting In re Chilowsky, 229 F.2d 457, 461, 108 USPQ 321, 325 (CCPA 1956)). The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970). Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1310, 115 USPQ2d 2012, 2023 (Fed. Cir. 2015) ( "Only a sufficient description enabling a person of ordinary skill in the art to carry out an invention is needed."). Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art. But because only an enabling disclosure is required, applicant need not describe all actual embodiments.”
The fact is the instant claims are not part of an undeveloped art but rather a well-studied and well developed art of immunity and all its possible facets and how they intersect and overlap. There is no enablement issues as applicant argues over that fact that the art is unpredictable.
Finally, applicant argues that they have provided superior unexpected results and point to the declaration’s section 7. This is not found persuasive. There is no unexpected result since the prior art already taught that the administration of IL-34 had similar effects on inflammatory disease. One of ordinary skill the art would expect the same effect since Amador-Patarroyo teaches that autoimmune uveitis is an inflammatory disease that is found within the patient populations with rheumatoid arthritis and systemic lupus erythematosus. See MPEP 716.02(c).II, which states: “Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness… In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (Evidence of improved feed efficiency in steers was not sufficient to rebut prima facie case of obviousness based on prior art which specifically taught the use of compound X537A to enhance weight gain in animals because the evidence did not show that a significant aspect of the claimed invention would have been unexpected.).”
MPEP 716.02 (b) teaches that the burden is on applicant to establish their results are unexpected and significant. The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."). Applicant is merely concluding that their results are superior without showing statistical and practical significance.
The evidence of unexpected results must be commensurate in scope with the claimed invention (see MPEP §716.02(d)). Evidence pertaining to secondary considerations must be taken into account whenever present; however, it does not necessarily control the obviousness conclusion. See, e.g., Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372, 82 USPQ2d 1321, 1339 (fed. Cir. 2007) (see MPEP §2145). Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977).
The evidence provided in the instant declaration shows that in the model of uveitis, a dose of 1X viral particles of AA V8-IL-34 was found to have a protective effect, and lowering disease severity in the right eye (AA V8-IL-34) compared to left eye (null vector, control). While this shows that the treatment is effective it does not in any way show that it is superior or unexpected.
Therefore, the argues are not found persuasive and the 103 obvious rejections are maintained.
Conclusion
No claims are allowed.
Advisory Information
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AURORA M. FONTAINHAS whose telephone number is 571-272-2952. The examiner can normally be reached on Monday - Friday (8AM - 4PM).
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, Jeffrey Stucker can be reached on (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675