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 .
Detailed Action
This action is in response to the papers filed May 28, 2026.
Amendments
Applicant's response and amendments, filed November 7, 2023, is acknowledged. Applicant has cancelled Claims 4, 7, 9-16, 24-38, 40-41, 43, 45-49, and 51-75, and amended Claims 1, 8, and 23.
Claims 1-3, 5-6, 8, 17-23, 39, 42, 44, and 50 are pending.
Election/Restrictions
Applicant has elected with traverse the invention of Group II, claim(s) 1-3, 5-8, 12-13, and 17-22, drawn to a method of treating an ocular condition in a subject in need thereof, the method comprising the step(s) of:
administering to at least one eye of the subject or to at least one lacrimal gland of the eye of the subject a recombinant adeno-associated virus (rAAV) virion comprising an AAV capsid and an expression cassette, wherein the expression cassette comprises a promoter operably linked to a polynucleotide encoding a neurotrophic factor.
Applicant argues that amended Claim 1 (Group II) and amended Claim 23 (Group I) now share the same technical feature of a NGF transgene, which the Examiner finds persuasive.
Non-elected Group I has been rejoined with elected Group II.
Applicant has elected the following species, wherein:
i) the alternative neurotrophic factor transgene is NGF;
ii) the alternative neurotrophic factor nucleic acid SEQ ID NO is SEQ ID NO:2, as recited in Claims 8 and 42;
iii) the alternative rAAV capsid serotype is AAV9 and its SEQ ID NO:14, as recited in Claims 17 and 44;
iv) the alternative ocular condition to be treated is neurotrophic keratitis, as recited in Claim 19; and
v) the alternative result to be achieved is reduction of one or more symptoms, as recited in Claim 20.
Response to Arguments
Applicant argues that Claims 39 and 50 recite SEQ ID NO:25, which is an expression vector comprising the neurotrophic transgene.
Applicant’s argument(s) has been fully considered, but is not persuasive. Applicant provides no objective evidence that the expression vector of SEQ ID NO:25 comprises the elected NGF polynucleotide sequence of SEQ ID NO:2.
Claims 1-3, 5-6, 8, 17-23, 39, 42, 44, and 50 are pending.
Claims 21-22, 39, and 50 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-3, 5-6, 8, 17-20, 23, 42, and 44 are under consideration.
Priority
This application is a 371 of PCT/US2022/027647 filed on May 4, 2022. Applicant’s claim for the benefit of a prior-filed application provisional application 63/185,889 filed on May 7, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
Applicant has filed an Information Disclosure Statement on November 7, 2023 that has been considered.
The signed and initialed PTO Forms 1449 are mailed with this action.
Claim Objections
1. Claim 3 is objected to because of the following informalities: the claim is internally redundant for reciting “main lacrimal gland” in both (a) and (b).
The Examiner suggests canceling (b).
Appropriate correction is required.
2. Claim 18 is objected to because of the following informalities:
The claim does not first identify the “CAG” promoter by its complete name prior to using its acronym. The abbreviation should be spelled out in the first appearance of the claims and should be followed by the abbreviation in parentheses.
Appropriate correction is required.
See, for example, Claim 1, Nerve Growth Factor (NGF).
See, even more specifically, for example, [0014].
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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.
3. Claim 5 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.
Claims 1-2 recite a method of treating an ocular condition in a subject, the method comprising the step of administering an rAAV virus to at least one lacrimal gland of a subject.
Claim 5 recites wherein the lacrimal gland is transduced with the rAAV virus.
Either this is an inherent property of (that naturally flows from) the rAAV virus [structure] and/or administration method step of Claims 1-2, or it is not, and something of the rAAV virus and/or administration method step must change.
To the extent it is an inherent property of (that naturally flows from) the product/method of Claims 1-2, then the instant claim fails to further limit Claims 1-2.
Furthermore, in regard to instant claims, it is noted that the “wherein the lacrimal gland is transduced with the rAAV virus” clause does not recite any additional structure(s) and/or active method step(s) but simply states a characterization or conclusion of the results of the positively recited rAAV virus and/or administration method step. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The specification fails to disclose an rAAV virus administered the lacrimal gland that does not transduce the lacrimal gland.
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
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.
4. Claim 6 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.
Claims 1-2 recite a method of treating an ocular condition in a subject, the method comprising the step of administering an rAAV virus to at least one lacrimal gland of a subject.
Claim 5 recites wherein the lacrimal gland is transduced with the rAAV virus.
Claim 6 recites wherein the transduced lacrimal gland expresses an effective amount of the neurotrophic factor into the tear film.
Either this is an inherent property of (that naturally flows from) the rAAV virus [structure] and/or administration method step of Claims 1-2 and 5, or it is not, and something of the rAAV virus and/or administration method step must change.
To the extent it is an inherent property of (that naturally flows from) the product/method of Claims 1-2 and 5, then the instant claim fails to further limit of Claims 1-2 and 5.
Furthermore, in regard to instant claims, it is noted that the “wherein the transduced lacrimal gland expresses an effective amount of the neurotrophic factor into the tear film” clause does not recite any additional structure(s) and/or active method step(s) but simply states a characterization or conclusion of the results of the positively recited rAAV virus and/or administration method step. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
Rocha et al (Transduction, Tropism, and Biodistribution of AAV Vectors in the Lacrimal Gland, Invest. Opthalmol. Vis. Sci. 52: 9567-9572, 2011; of record in IDS) is considered relevant prior art for having taught that AAV transgene-encoded secreted proteins are secreted into the tears from the transduced LG tissues (e.g. pg 9571, col. 2, “secreted into the tears”, “transduction of LG resulted in detection of the recombinant protein… in the tears”).
The specification fails to disclose a lacrimal gland transduced with a rAAV virus that does not express an effective amount of the neurotrophic factor into the tear film, yet is able to treat the ocular condition, as required by independent Claim 1.
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
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.
5. Claim(s) 5-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-2 recite a method of treating an ocular condition in a subject, the method comprising the step of administering an rAAV virus to at least one lacrimal gland of a subject.
Claim 5 recites wherein the lacrimal gland is transduced with the rAAV virus.
Either this is an inherent property of (that naturally flows from) the rAAV virus and/or administration method step of Claims 1-2, or it is not, and something of the rAAV virus and/or administration method step must change.
The claim denotes that not all of the rAAV viruses and/or method steps of Claims 1-2 are able to achieve the functional property(ies) recited in the dependent Claim 5.
To the extent it is not an inherent property (that naturally flows) from the rAAV virus and/or administration method step of Claims 1-2, then something must change. The claim is considered to lack adequate written description for failing to recite the structure(s) and/or method step change(s) that is necessary and sufficient to cause the recited functional language.
The limitation “wherein the lacrimal gland is transduced with the rAAV virus” clause does not recite any additional structure(s) and/or active method step(s) but simply states a characterization or conclusion of the results of the positively recited rAAV virus and/or administration method step. The specification fails to disclose what structural changes to the rAAV virus and/or what changes to the method step of administering to the lacrimal gland is/are necessary and sufficient to cause the recited lacrimal gland transduction, and thus the ordinary artisan would not know what modification(s) must be made in order to fulfill the instant recitation.
Claim 6 recites wherein the transduced lacrimal gland expresses an effective amount of the neurotrophic factor into the tear film.
Either this is an inherent property of (that naturally flows from) the rAAV virus and/or administration method step of Claims 1-2 and 5, or it is not, and something of the rAAV virus and/or administration method step must change.
The claim denotes that not all of the rAAV viruses and/or method steps of Claims 1-2 and 5 are able to achieve the functional property(ies) recited in the dependent Claim 6.
To the extent it is not an inherent property (that naturally flows) from the rAAV virus and/or administration method step of Claims 1-2 and 5, then something must change. The claim is considered to lack adequate written description for failing to recite the structure(s) and/or method step change(s) that is necessary and sufficient to cause the recited functional language.
The limitation “wherein the transduced lacrimal gland expresses an effective amount of the neurotrophic factor into the tear film” clause does not recite any additional structure(s) and/or active method step(s) but simply states a characterization or conclusion of the results of the positively recited rAAV virus and/or administration method step. The specification fails to disclose what structural changes to the rAAV virus and/or what changes to the method step of administering to the lacrimal gland is/are necessary and sufficient to cause the recited lacrimal gland transduction, and thus the ordinary artisan would not know what modification(s) must be made in order to fulfill the instant recitation.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims fail to recite, and the specification fails to disclose, a first rAAV administered to the lacrimal gland that does not transduce the lacrimal gland, yet is able to treat the ocular condition, as required by independent Claim 1, as opposed to a second rAAV administered to the lacrimal gland that necessarily and predictably transduces the lacrimal gland, and is able to treat the ocular condition, as required by independent Claim 1, for example.
The claims fail to recite, and the specification fails to disclose, a first lacrimal gland transduced with a rAAV virus that does not express an effective amount of the neurotrophic factor into the tear film, yet is able to treat the ocular condition, as required by independent Claim 1, as opposed to a second lacrimal gland transduced with a rAAV virus that necessarily and predictably expresses an effective amount of the neurotrophic factor into the tear film, and is able to treat the ocular condition, as required by independent Claim 1, for example.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not clarify the nature of the corresponding structure that is necessary and sufficient to cause the recited functional language.
6. Claim 20 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 1 recites a method of treating an ocular condition in a subject, the method comprising the step of administering an rAAV virus to at least one eye or at least one lacrimal gland of a subject.
Claim 20 recites wherein one or more symptoms of the ocular condition are reduced compared to symptoms before administration of the rAAV virus.
Either this is an inherent property of (that naturally flows from) the rAAV virus and/or administration method step of Claim 1, or it is not, and something of the rAAV virus and/or administration method step must change.
To the extent it is an inherent property of (that naturally flows from) the product/method of Claim 1, then the instant claim fails to further limit Claim 1.
Furthermore, in regard to instant claims, it is noted that the “wherein one or more symptoms of the ocular condition are reduced compared to symptoms before administration of the rAAV virus” clause does not recite any additional structure(s) and/or active method step(s) but simply states a characterization or conclusion of the results of the positively recited rAAV virus and/or administration method step. Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
The specification fails to disclose an rAAV virus administered the eye or lacrimal gland, thereby treating the ocular condition (Claim 1) that does not also reduce one or more symptoms of the ocular condition, by however minor amount that might be, as compared to the absence of the rAAV gene therapy (Claim 20).
'Even if such a phrase did hold patentable weight, the phrase would likely be rejected under 35 USC 112(b) for being indefinite because such a phrase would amount to a 'functional limitation' whereby one of ordinary skill in the art would essentially need to 'guess' what steps must occur in the claim, in addition to the positively-recited method steps, in order to result in 'wherein the....' (the 'intended result' phrase in the claim).
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.
7. Claim(s) 20 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a method of treating an ocular condition in a subject, the method comprising the step of administering an rAAV virus to at least one eye or at least one lacrimal gland of a subject.
Claim 20 recites wherein one or more symptoms of the ocular condition are reduced compared to symptoms before administration of the rAAV virus.
Either this is an inherent property of (that naturally flows from) the rAAV virus [structure] and/or administration method step of Claim 1, or it is not, and something of the rAAV virus and/or administration method step must change.
The claim denotes that not all of the rAAV viruses and/or method steps of Claim 1 are able to achieve the functional property(ies) recited in the dependent Claim 20.
To the extent it is not an inherent property (that naturally flows) from the rAAV virus and/or administration method step of Claim 1, then something must change. The claim is considered to lack adequate written description for failing to recite the structure(s) and/or method step change(s) that is necessary and sufficient to cause the recited functional language.
The limitation “wherein one or more symptoms of the ocular condition are reduced compared to symptoms before administration of the rAAV virus” clause does not recite any additional structure(s) and/or active method step(s) but simply states a characterization or conclusion of the results of the positively recited rAAV virus and/or administration method step. The specification fails to disclose what structural changes to the rAAV virus and/or what changes to the method step of administering to the lacrimal gland is/are necessary and sufficient to cause the recited lacrimal gland transduction, and thus the ordinary artisan would not know what modification(s) must be made in order to fulfill the instant recitation.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims fail to recite, and the specification fails to disclose, a first rAAV administered to the eye and/or lacrimal gland that does not reduce one or more symptoms of the ocular condition as compared to symptoms of the ocular condition, by however minor amount that might be, before administration of the rAAV virus, yet is able to treat the ocular condition, as required by independent Claim 1, as opposed to a second rAAV administered to the eye and/or lacrimal gland that necessarily and predictably reduces one or more symptoms of the ocular condition, by however minor amount that might be, as compared to symptoms before administration of the rAAV virus, and is able to treat the ocular condition, as required by independent Claim 1, for example.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
8. Claim(s) 23 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramirez et al (Adeno-Associated Virus Vector Expressing Nerve Growth Factor Enhances Cholinergic Axonal Sprouting after Cortical Injury in Rats, J. Neurosci. 23(7): 2797-2803, 2003).
With respect to Claim 23, Ramirez et al is considered relevant prior art for having taught an rAAV virus whose genome encodes a NGF transgene operably linked to a promoter (e.g. Figure 1; pg 2798, Materials and Methods).
Thus, Ramirez et al anticipate the claim.
9. Claim(s) 23 and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kipps et al (U.S. 2006/0183199).
With respect to Claims 23 and 42, Kipps et al is considered relevant prior art for having disclosed an expression vector (e.g. [0019]) encoding a NGF transgene (SEQ ID NO:23) [0081] operably linked to a promoter (e.g. [0098-101]), wherein said expression vector includes rAAV [0104]).
The NGF nucleotide sequence of SEQ ID NO:23 is 100% to instant SEQ ID NO:2.
Thus, Kipps et al anticipate the claims.
10. Claim(s) 23 and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tuszyncki (U.S. 2007/0249554).
With respect to Claims 23 and 42, Tuszyncki is considered relevant prior art for having disclosed a rAAV expression vector whose genome encodes a NGF transgene operably linked to a promoter (e.g. Example 1), wherein said NGF transgene comprises the nucleotide sequence of SEQ ID NO:2 (e.g. [0065], reference to GenBank X52599), which is 100% to instant SEQ ID NO:2 (search results available in SLIC).
Thus, Tuszyncki anticipate the claims.
11. Claim(s) 1, 18, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Danos et al (U.S. 2022/0143221; priority to April 3, 2019).
With respect to Claim 1, Danos et al is considered relevant prior art for having disclosed a method of treating an ocular disorder in a subject, the method comprising the step of administering to the eye of said subject a rAAV virus (e.g. Abstract; Figure 4; claim 39) whose genome encodes and expresses NGF (e.g. [0212, 523]; claim 26).
Danos et al disclosed wherein the rAAV is rAAV9 serotype (e.g. [0049, 747, 753], “AAV9”).
With respect to Claim 18, Danos et al disclosed wherein the promoter is a CAG promoter (e.g. [0033, 347], “CAG promoter”).
With respect to Claim 20, the claim is not considered to further limit the independent claim. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection above.
To the extent Applicant argues otherwise, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description rejection above.
Thus, Danos et al anticipate the claims.
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 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 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.
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(a) 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.
[Product]
12. Claims 23, 42, and 44 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Tuszyncki (U.S. 2007/0249554; of record) in view of Wright et al (U.S. Patent 9,408,904).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claims 23 and 42, Tuszyncki is considered relevant prior art for having disclosed a rAAV expression vector whose genome encodes a NGF transgene operably linked to a promoter (e.g. Example 1), wherein said NGF transgene comprises the nucleotide sequence of SEQ ID NO:2 (e.g. [0065], reference to GenBank X52599), which is 100% to instant SEQ ID NO:2 (search results available in SLIC).
Tyszynski do not disclose wherein the rAAV is rAAV9.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 44, Wright et al is considered relevant prior art for having disclosed rAAV vectors comprising a NGF transgene (e.g. Figure 1; col. 9, line 13; claim 9), wherein said rAAV is an rAAV9 virus (e.g. col. 2, lines 43-45; claim 6).
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and the creation of rAAV viral expression vectors. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first rAAV capsid serotype, as disclosed by Tuszyncki, with a second rAAV capsid serotype, including rAAV9 capsid serotype, as disclosed by Wright et al, in a rAAV viral vector whose genome encodes and expresses NGF, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first rAAV capsid serotype with a second rAAV capsid serotype, including rAAV9 capsid serotype in a rAAV viral vector whose genome encodes and expresses NGF because those of ordinary skill in the art have long-recognized the rAAV capsid serotypes are substitutable, and Wright et al disclosed a defined list of 6 rAAV capsid serotype options from which to choose (e.g. col. 2, lines 43-45; claim 6).
It would have been obvious to one of ordinary skill in the art to choose from a finite number of identified, predictable options because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.”
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
[Method of Use]
13. Claims 1-3, 5-6, 8, 18, and 20 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Danos et al (U.S. 2022/0143221; priority to April 3, 2019; of record) in view of Tuszyncki (U.S. 2007/0249554; of record), Lambiase et al (U.S. 2009/0118177), and Rocha et al (2011; of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 1, Danos et al is considered relevant prior art for having disclosed a method of treating an ocular disorder in a subject, the method comprising the step of administering to the eye of said subject a rAAV virus (e.g. Abstract; Figure 4; claim 39) whose genome encodes and expresses NGF (e.g. [0212, 523]; claim 26).
Danos et al disclosed wherein the rAAV is rAAV9 serotype (e.g. [0049, 747, 753], “AAV9”).
Danos et al do not disclose ipsis verbis a reduction to practice of an rAAV-NGF.
However, 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).
A reference contains an "enabling disclosure" if the public was in possession of the claimed invention before the date of invention. "Such possession is effected if one of ordinary skill in the art could have combined the publication's description of the invention with his [or her] own knowledge to make the claimed invention." In re Donohue, 766 F.2d 531, 226 USPQ 619 (Fed. Cir. 1985).
Tuszyncki is considered relevant prior art for having disclosed a rAAV expression vector whose genome encodes a NGF transgene operably linked to a promoter (e.g. Example 1), wherein said NGF transgene comprises the nucleotide sequence of SEQ ID NO:2 (e.g. [0065], reference to GenBank X52599), which is 100% to instant SEQ ID NO:2 (search results available in SLIC).
Thus, no undue experimentation is required.
Danos et al do not disclose administering the rAAV-NGF to the lacrimal gland of the subject.
However, prior to the effective filing date of the instantly claimed invention, Lambiase et al is considered relevant prior art for having disclosed a method of treating an ocular disorder in a subject (e.g. [0021], “topical administration of NGF can successfully solve ocular surface pathologies, and, … internal ocular tissues; NGF turned out to be suitable for successfully treating ophthalmic pathologies”), the method comprising the step of administering NGF to the ocular surface (e.g. Abstract).
Rocha et al is considered relevant prior art for having taught a method of delivering rAAV9 encoding and expressing the artisan’s transgene of interest to the main lacrimal gland (LG) of a subject (entire paper).
Rocha et al taught that LG gene delivery by rAAV vectors is safe and well-tolerated (e.g. Abstract Conclusion).
Rocha et al taught that AAV transgene-encoded secreted proteins are secreted into the tears from the transduced LG tissues (e.g. pg 9571, col. 2, “secreted into the tears”, “transduction of LG resulted in detection of the recombinant protein… in the tears”).
Rocha et al taught that rAAV9 demonstrated the fastest and most intense LG transduction (e.g. pg 9569, col. 1; pg 9571, col. 2, “more efficient with AAV9”).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first route of administering a rAAV-NGF virus, as disclosed by Danos et al, with a second route of administering a rAAV-NGF virus, to wit, to the main lacrimal gland, as taught by Rocha et al, in a method of treating an ocular disorder in a subject comprising the step of administering to the eye or lacrimal gland of said subject a rAAV viral vector whose genome encodes and expresses NGF, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first route of administering a rAAV-NGF virus with a second route of administering a rAAV-NGF virus, to wit, to the main lacrimal gland, in a method of treating an ocular disorder in a subject comprising the step of administering to the eye or lacrimal gland of said subject a rAAV viral vector whose genome encodes and expresses NGF because those of ordinary skill in the art previously recognized the scientific and technical concepts that:
i) NGF is useful for the treatment of an ocular disorder in a subject (Lambiase et al; Danos et al);
ii) NGF expression via rAAV had been successfully reduced to practice (Tuszyncki);
iii) NGF expression via rAAV is useful for the treatment of an ocular disorder in a subject (Danos et al); and
iv) administration of rAAV expressing the artisan’s protein of interest to the lacrimal gland of a subject had been successfully reduced to practice, whereby LG gene delivery by rAAV vectors is safe and well-tolerated (e.g. Rocha et al, Abstract Conclusion) and AAV transgene-encoded secreted proteins are secreted into the tears from the transduced LG tissues (e.g. Rocha et al, pg 9571, col. 2, “secreted into the tears”, “transduction of LG resulted in detection of the recombinant protein… in the tears”),
whereby those of ordinary skill in the art would have immediately understood that expression of the rAAV-encoded NGF in the tear film would essentially recapitulate the topical application of purified, recombinant NGF (per Lambiase et al, e.g. Abstract, “eye-drops or ointment”).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 8, Tuszyncki is considered relevant prior art for having disclosed a rAAV expression vector whose genome encodes a NGF transgene operably linked to a promoter (e.g. Example 1), wherein said NGF transgene comprises the nucleotide sequence of SEQ ID NO:2 (e.g. [0065], reference to GenBank X52599), which is 100% to instant SEQ ID NO:2 (search results available in SLIC).
It is axiomatic that the NGF nucleotide sequence of SEQ ID NO:2 encodes the NGF amino acid sequence of SEQ ID NO:1.
With respect to Claims 5-6, Claims 5-6 are not considered to further limit Claims 1-2. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection above.
To the extent Applicant argues otherwise, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description rejection above.
Nevertheless, Rocha et al taught a method of delivering rAAV9 to the lacrimal gland of a subject (entire paper). Rocha et al taught that AAV transgene-encoded secreted proteins are secreted into the tears from the transduced LG tissues (e.g. pg 9571, col. 2, “secreted into the tears”, “transduction of LG resulted in detection of the recombinant protein… in the tears”).
With respect to Claim 18, Danos et al disclosed wherein the promoter is a CAG promoter (e.g. [0033, 347], “CAG promoter”).
With respect to Claim 20, the claim is not considered to further limit the independent claim. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection above.
To the extent Applicant argues otherwise, see 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description rejection above.
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
14. Claim(s) 17 is rejected under AIA 35 U.S.C. 103 as being unpatentable over Danos et al (U.S. 2022/0143221; priority to April 3, 2019; of record) in view of Tuszyncki (U.S. 2007/0249554; of record), Lambiase et al (U.S. 2009/0118177; of record), and Rocha et al (2011; of record in IDS), as applied to Claims 1-3, 5-6, 8, 18, and 20 above, and in further view of GenBank Q6JC40 (rAAV9 capsid, 2006).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Danos et al disclosed wherein the rAAV is rAAV9 serotype (e.g. [0049, 747, 753], “AAV9”).
Rocha et al taught wherein the rAAV is rAAV9 serotype (e.g. pg 9569, col. 1; pg 9571, col. 2, “more efficient with AAV9”).
Neither Danos et al, Tuzzyncki, Lambiase et al, nor Rocha et al teach/disclose wherein the rAAV9 has the AAV9 capsid amino acid sequence of SEQ ID NO:14.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim 17, GenBank Q6JC40 is considered relevant prior art for having disclosed an AAV9 capsid having the amino acid sequence that is 100% identical to instant SEQ ID NO:14.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first AAV9 capsid, as taught/disclosed by Danos et al and/or Rocha et al, with a second AAV9 capsid having the amino acid sequence of instant SEQ ID NO:14, as taught by GenBank Q6JC40, in a method of treating an ocular disorder in a subject comprising the step of administering to the eye or lacrimal gland of said subject a rAAV viral vector whose genome encodes and expresses NGF, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first AAV9 capsid with a second AAV9 capsid having the amino acid sequence of instant SEQ ID NO:14 in a method of treating an ocular disorder in a subject comprising the step of administering to the eye or lacrimal gland of said subject a rAAV viral vector whose genome encodes and expresses NGF because those of ordinary skill in the art had long-recognized, about 15 years prior to the effective filing date of the instantly claimed invention(!), that AAV9 capsid protein naturally comprises the amino acid sequence of SEQ ID NO:14.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
15. Claim(s) 19 is rejected under AIA 35 U.S.C. 103 as being unpatentable over Danos et al (U.S. 2022/0143221; priority to April 3, 2019; of record) in view of Tuszyncki (U.S. 2007/0249554; of record), Lambiase et al (U.S. 2009/0118177; of record), and Rocha et al (2011; of record in IDS), as applied to Claims 1-3, 5-6, 8, 18, and 20 above, and in further view of Bonini et al (Topical Treatment with Nerve Growth Factor for Neurotrophic Keratitis, Ophthalmology 102(7): 1347-1352, 2000; co-authors to Lambiase et al; hereafter Lambiase-2).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Danos et al, Tuszyncki, Lambiase et al, nor Rocha et al teach/disclose wherein the ocular disease/disorder/condition is neurotrophic keratitis.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim 19, Lambiase-2 is considered relevant prior art for having taught a method of treating neurotrophic keratitis in a subject in need, the method comprising the step of topically administering recombinant NGF (e.g. Title), whereby the NGF treatment resulted in “complete resolution of the persistent epithelial defect” and “improved corneal sensitivity and visual acuity” (e.g. Abstract Results).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first ocular disorder, as taught/disclosed by Danos et al and/or Lambiase et al, with a second ocular disorder, to wit, neurotrophic keratitis, as taught by Lambiase-2, in a method of treating an ocular disorder in a subject comprising the step of administering to the eye or lacrimal gland of said subject a rAAV viral vector whose genome encodes and expresses NGF, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first ocular disorder with a second ocular disorder, to wit, neurotrophic keratitis, in a method of treating an ocular disorder in a subject comprising the step of administering to the eye or lacrimal gland of said subject a rAAV viral vector whose genome encodes and expresses NGF because those of ordinary skill in the art had long-recognized, about 19 years prior to the effective filing date of the instantly claimed invention(!), that NGF is therapeutic for the treatment of neurotrophic keratitis.
Those of ordinary skill in the art previously recognized that administration of rAAV expressing the artisan’s protein of interest to the lacrimal gland of a subject had been successfully reduced to practice, whereby LG gene delivery by rAAV vectors is safe and well-tolerated (e.g. Rocha et al, Abstract Conclusion) and AAV transgene-encoded secreted proteins are secreted into the tears from the transduced LG tissues (e.g. Rocha et al, pg 9571, col. 2, “secreted into the tears”, “transduction of LG resulted in detection of the recombinant protein… in the tears”),
whereby those of ordinary skill in the art would have immediately understood that expression of the rAAV-encoded NGF in the tear film would essentially recapitulate the topical application of purified, recombinant NGF (per Lambiase et al, e.g. Abstract, “eye-drops or ointment”; Lambiase-2, e.g. Abstract, “Nerve growth factor eye drops”).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
Citation of Relevant Prior Art
16. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
GenBank X52599 (human NGF, 2008), as disclosed by Tuszyncki (U.S. 2007/0249554; Example 1, [0065], reference to GenBank X52599) is considered relevant prior art for having taught a NGF-encoding nucleic acid sequence that is 100% identical to instant SEQ ID NO:2 (search results available in SLIC).
Conclusion
17. No claims are allowed.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
Prosecution Insights