DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/7/25 has been entered.
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 5/7/25 are acknowledged. Any objection or rejection from the 11/7/24 office action that is not addressed below is withdrawn based on the amendments and/or arguments.
Previously, human Thy-1 in which the last 31 amino acids have been deleted was elected (i.e. residues 1-130).
As amended, the claims recite that the fragment is 30-50 amino acids in length (and is a fusion protein). As such, the elected species no longer reads on the claims. In accord with MPEP 803.02 III A the search was extended to the extent necessary to determine patentability.
Claims 1, 12-13, 15 and 17-34 have been canceled.
Claims 2-11, 14, 16 and 35 are being examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/7/25 has been considered by the examiner.
Priority
This application claims benefit of 63/107,102 10/29/20.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/107,102, fails to provide adequate written description in the manner provided by the first paragraph of 35 U.S.C. 112 for claims 2-11, 14, 16 and 35 of this application.
Claims 2, 8-9 and dependents encompass ‘fragment is 30-50 amino acids in length’.
Application No. 63/107,102 does not use the phrase ‘30-50 amino acids in length’. Application No. 63/107,102 refers to soluble Thy-1 (abstract). The genus of ‘fragment is 30-50 amino acids in length’ is much broader than soluble Thy-1.
It is noted that section 2152.01 of the MPEP sets forth the method to determine the effective filing date. In particular, ‘If the application properly claims benefit under 35 U.S.C. 119(e) to a provisional application, the effective filing date is the filing date of the claimed invention is the filing date of the provisional application for any claims which are fully supported under 35 U.S.C. 112 by the provisional application.’. In the instant case, claims 2-11, 14 and 35 are not fully supported by the provisional Application No. 63/107,102 for at least the reasons discussed above. As such, for purposes of searching for prior art, a priority date of 10/29/21 is used for claims 2-11, 14, 16 and 35.
Claim Rejections - 35 USC § 103
Claims were previously rejected under 103 based on the references cited below. The rejections have been updated.
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.
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.
Claim(s) 2-11, 14, 16 and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tan et al. (‘Soluble Thy-1 reverses lung fibrosis via its integrin-binding motif’ JCI Insight November 1 2019, 13 pages; ‘Tan’; first cited 4/5/24) in view of Phipps et al. (US 2015/0283205; ‘Phipps’ cited with IDS 4/20/23) in view of Haber (WO 99/45951 09-99).
The priority date of the instant claims is set forth in the priority section above. The first page of Tan lists a publication date of November 1, 2019.
Tan teach that soluble Thy-1 reverses lung fibrosis (title). Tan teach that the soluble form of human Thy-1 (sThy-1) was administered as a fusion to mice after lung fibrosis had been established (page 4 first paragraph). Tan teach that the treatment significantly reduced fibrosis scores (page 4 first paragraph). Figure 4 shows that the administration was i.v. (page 6). Tan teach that sThy-1 reveres lung fibrosis in mice specifically mice with alveolar septal thickening (page 5 last paragraph). Tan teach that sThy-1-IgGFc was administered i.v. to mice which showed resolution of airway and alveolar parenchymal fibrotic response (pages 5-6 connecting paragraph). Tan specifically uses human lung fibroblasts in an in vitro model (pages 4-5 connecting paragraph). Tan states that sThy-1 as useful in a disease such as IPF (page 9 2nd complete paragraph). Tan states that Thy-1 expression was diminished in self-resolving fibrosis and that in progressive fibrosis Thy-1 was silenced (page 2 2nd paragraph). Tan refers to organ fibrosis (page 1 last paragraph).
Tan does not administer to a human nor does Tan teach delivery by inhalation or teach the specific fragments as claimed.
Phipps teach Thy1 used in therapies specifically those involving tissue accumulation (title). Phipps shows the domain of soluble Thy1 (figure 1) and teach that Thy1 is known (sections 0013 and 0041). Phipps recognizes human Thy1 (sections 0045-0046) and teach polypeptides in which the GPI anchor is removed (section 0054). Phipps recognizes that residues 1-19 of Thy-1 is a signal peptide which is cleaved to form the mature and soluble form (figure 1a). Phipps teach that the polypeptides can be prepared by known methods including peptide synthesis or recombinant expression (section 0061). Phipps recognizes that the administration can be by inhalation or intravenous (section 0086) and recognize the use of an amount effective for the desired result (section 0088). Phipps recognizes that the Thy1 polypeptide can be part of a fusion (section 0050). Phipps suggest the use of a fusion protein for longer half-life and specifically suggest human serum albumin (section 0050). Phipps recognize human tissues (section 0004) and human subjects (section 0081) as well as the heart and liver (sections 0004 and 0081).
Haber teach methods of inhibiting angiogenesis by administering a compound that inhibits Thy-1-associated proliferation of endothelial cells (abstract and page 18 first 2 paragraphs). Haber teach that the compound comprise an extracellular fragment of Thy-1 (claim 4). Haber teach an example with a rat extracellular fragment of residues Gln1-Gly113 (page 13 last paragraph). Haber teach human as a source of the Thy-1 (page 2 first paragraph and amino acids 1-111 of SEQ ID NO: 2) which starts at the first residue after the signal sequence (see Table 3 on page 4). With respect to the fragments, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length (page 18 2nd paragraph). Haber teach that peptides can be generated by methods known in the art (page 18 2nd paragraph). Haber teach that the Thy-1 fragment can be in the form of a fusion protein (page 21 lines 27-30) and recognize the presence of proteases (page 1 lines 13-16). Haber recognizes that Cys111 in Thy1 is a possible site of undesired nonspecific disulfide linkages (page 15 first paragraph). Haber teach pharmaceutical compositions comprising a pharmaceutically acceptable carrier (pages 18-19 connecting paragraph). Haber teach that the compositions may be delivered by a catheter and also teach that the composition can be delivered by a device with the therapeutic compound (page 19 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Tan based on the specific teachings and suggestions of Tan. Tan teach that soluble Thy-1 reverses lung fibrosis (title). Tan specifically uses human lung fibroblasts in an in vitro model (pages 4-5 connecting paragraph). Tan states that sThy-1 as useful in a disease such as IPF (page 9 2nd complete paragraph). Tan states that Thy-1 expression was diminished in self-resolving fibrosis and that in progressive fibrosis Thy-1 was silenced (page 2 2nd paragraph and abstract). Thus, one would have been motivated to treat such subjects. With respect to the mode of administration, Phipps teach Thy1 used in therapies (title) and recognizes that the administration can be by inhalation or intravenous (section 0086). One would have been motivated to use the teachings of Phipps because Phipps also teach the Thy1 polypeptide. Phipps shows the domain of soluble Thy1 (figure 1) and teach that Thy1 is known (sections 0013 and 0041). Phipps recognizes human Thy1 (sections 0045-0046) and teach polypeptides in which the GPI anchor is removed (section 0054). Phipps recognizes that the Thy1 polypeptide can be part of a fusion (section 0050). Phipps teach the human Thy1 protein architecture (figure 1a and caption section 0017) and suggest the use of a fusion protein for longer half-life and specifically suggest human serum albumin (section 0050). Thus, one would have been motivated to fuse the Thy-1 fragment to human serum albumin. With respect to the Thy-1 fragments, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length (page 18 2nd paragraph). Haber teach a human source of the Thy-1 (page 2 first paragraph and amino acids 1-111 of SEQ ID NO: 2) which starts at the first residue after the signal sequence (see Table 3 on page 4). Phipps recognizes that residues 1-19 of Thy-1 are a signal peptide which is cleaved to form the mature and soluble form (figure 1a) which is consistent with SEQ ID NO:2 of Haber. Thus based on the suggestion to use 50 contiguous amino acids (page 18 2nd paragraph of Haber), one would have been motivated to make fragments including a 50 residue fragment containing residues 1-50 of SEQ ID NO:2 of Haber. Further, since Haber recognizes that Cys111 in Thy1 is a possible site of undesired nonspecific disulfide linkages (page 15 first paragraph) one would have been motivated to make peptides comprising fragments in which Cys111 has been deleted. Since Haber teach pharmaceutical compositions comprising a pharmaceutically acceptable carrier (pages 18-19 connecting paragraph) one would have been motivated to make such compositions. Since Haber teach that the compositions may be delivered by a catheter and also teach that the composition can be delivered by a device with the therapeutic compound (page 19 first paragraph) one would have been motivated to prepare such compositions. One would have had a reasonable expectation of success since Haber teach that peptides can be generated by methods known in the art (page 18 2nd paragraph) and Haber teach generation of fusions (page 15). Phipps recognizes the use of an amount effective for the desired result (section 0088). Based on the beneficial results taught by Tan and since Tan refers to organ fibrosis (page 1 last paragraph) one would be motivated to administer to other organs. Phipps recognize human tissues (section 0004) and human subjects (section 0081) as well as the heart and liver (sections 0004 and 0081). One would have had a reasonable expectation of success since Tan teach that soluble Thy-1 reverses lung fibrosis (title). Further, Phipps teach that the polypeptides can be prepared by known methods including peptide synthesis or recombinant expression (section 0061) and recognizes that the administration can be by inhalation or intravenous (section 0086).
In relation to the subject of claims 2 and 8-9, Tan teach that soluble Thy-1 reverses lung fibrosis (title). Tan teach that the treatment significantly reduced fibrosis scores (page 4 first paragraph). Figure 4 shows that the administration was i.v. (page 6). Tan teach that sThy-1 reveres lung fibrosis in mice specifically mice with alveolar septal thickening (page 5 last paragraph). Tan teach administration i.v. to mice which showed resolution of airway and alveolar parenchymal fibrotic response (pages 5-6 connecting paragraph).
In relation to the polypeptide of claims 2, 8-9 and 14, as discussed above the prior art suggests (residues 1-50 of SEQ ID NO:2 of Haber) fusion to human serum albumin. Residues 16-18 of SEQ ID NO:2 are RLD and residues 37-41 are RETKK (interpreted to be syndecan-4 binding domain). Phipps teach polypeptides in which the GPI anchor is removed (section 0054).
In relation to claims 3-4, Tan expressly recites self-resolving and nonresolving (abstract). Tan states that Thy-1 expression was diminished in self-resolving fibrosis and that in progressive fibrosis Thy-1 was silenced (page 2 2nd paragraph).
In relation to claim 5, Tan teach that soluble Thy-1 reverses lung fibrosis (title).
In relation to claim 6, Tan recites IPF (idiopathic pulmonary fibrosis) (page 2 line 3). Tan states that sThy-1 as useful in a disease such as IPF (page 9 2nd complete paragraph).
In relation to claim 7, Tan refers to organ fibrosis (page 1 last paragraph). Phipps recognize human tissues (section 0004) and human subjects (section 0081) as well as the heart and liver (sections 0004 and 0081).
In relation to claim 10, Phipps recognizes that the administration can be by inhalation (section 0086).
In relation to claims 11 and 35, Figure 4 of Tan shows that the administration was i.v. (page 6). Tan teach that administration i.v. to mice which showed resolution of airway and alveolar parenchymal fibrotic response (pages 5-6 connecting paragraph).
In relation to claim 16, Tan specifically uses human lung fibroblasts in an in vitro model (pages 4-5 connecting paragraph). Phipps recognize human tissues (section 0004) and human subjects (section 0081).
Claim(s) 2-11, 14, 16 and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (‘Soluble Thy-1 reverses myofibroblast differentiation and progressive pulmonary fibrosis via its integrin-binding domain’ American Journal of Respiratory and Critical Care Medicine v197 2018 A4343, printed as pages 1-3; ‘Wong’; first cited 4/5/24) in view of Phipps et al. (US 2015/0283205; ‘Phipps’ cited with IDS 4/20/23) in view of Haber (WO 99/45951 09-99).
Wong teach that soluble Thy-1 reverses pulmonary fibrosis via its integrin-binding domain (title). Wong recites that the integrin-like binding domain is RLD (page 2). Wong teach that the antifibrotic efficacy of sThy1 was examined in a murine model of pulmonary fibrosis (page 2). Wong teach that mice in which fibrosis was established were administered Thy1-IgGFc which reduced fibrosis scores and lung dysfunction (page 2). Wong refers to self-limited fibrosis as well as persistent and IPF (idiopathic pulmonary fibrosis) (page 2). Wong teach that exogenous sThy1 has therapeutic effects on fibrosis of different origins (page 2). Wong mentions the use of human lung fibroblasts (page 2).
Wong does not administer to a human nor does Wong teach delivery by inhalation or the specific fragments claimed.
Phipps teach Thy1 used in therapies specifically those involving tissue accumulation (title). Phipps shows the domain of soluble Thy1 (figure 1) and teach that Thy1 is known (sections 0013 and 0041). Phipps recognizes human Thy1 (sections 0045-0046) and teach polypeptides in which the GPI anchor is removed (section 0054). Phipps recognizes that residues 1-19 of Thy-1 is a signal peptide which is cleaved to form the mature and soluble form (figure 1a). Phipps teach that the polypeptides can be prepared by known methods including peptide synthesis or recombinant expression (section 0061). Phipps recognizes that the administration can be by inhalation or intravenous (section 0086) and recognize the use of an amount effective for the desired result (section 0088). Phipps recognizes that the Thy1 polypeptide can be part of a fusion (section 0050). Phipps suggest the use of a fusion protein for longer half-life and specifically suggest human serum albumin (section 0050). Phipps recognize human tissues (section 0004) and human subjects (section 0081) as well as the heart and liver (sections 0004 and 0081).
Haber teach methods of inhibiting angiogenesis by administering a compound that inhibits Thy-1-associated proliferation of endothelial cells (abstract and page 18 first 2 paragraphs). Haber teach that the compound comprise an extracellular fragment of Thy-1 (claim 4). Haber teach an example with a rat extracellular fragment of residues Gln1-Gly113 (page 13 last paragraph). Haber teach human as a source of the Thy-1 (page 2 first paragraph and amino acids 1-111 of SEQ ID NO: 2) which starts at the first residue after the signal sequence (see Table 3 on page 4). With respect to the fragments, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length (page 18 2nd paragraph). Haber teach that peptides can be generated by methods known in the art (page 18 2nd paragraph). Haber teach that the Thy-1 fragment can be in the form of a fusion protein (page 21 lines 27-30) and recognize the presence of proteases (page 1 lines 13-16). Haber recognizes that Cys111 in Thy1 is a possible site of undesired nonspecific disulfide linkages (page 15 first paragraph). Haber teach pharmaceutical compositions comprising a pharmaceutically acceptable carrier (pages 18-19 connecting paragraph). Haber teach that the compositions may be delivered by a catheter and also teach that the composition can be delivered by a device with the therapeutic compound (page 19 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Wong based on the specific teachings and suggestions of Wong. Wong teach that soluble Thy-1 reverses pulmonary fibrosis (title). Wong teach that exogenous sThy1 has therapeutic effects on fibrosis of different origins (page 2). Since Wong specifically mentions self-limited fibrosis as well as persistent and IPF (idiopathic pulmonary fibrosis) (page 2) one would have been motivated to treat such subjects. Wong mentions the use of human lung fibroblasts (page 2). Based on the positive results and the use of human lungs one would have been motivated to administer to humans. Thus, one would have been motivated to treat such subjects. With respect to the mode of administration, Phipps teach Thy1 used in therapies (title) and recognizes that the administration can be by inhalation or intravenous (section 0086). One would have been motivated to use the teachings of Phipps because Phipps also teach the Thy1 polypeptide. Phipps shows the domain of soluble Thy1 (figure 1) and teach that Thy1 is known (sections 0013 and 0041). Phipps recognizes human Thy1 (sections 0045-0046) and teach polypeptides in which the GPI anchor is removed (section 0054). Phipps recognizes that the Thy1 polypeptide can be part of a fusion (section 0050). Phipps teach the human Thy1 protein architecture (figure 1a and caption section 0017) and suggest the use of a fusion protein for longer half-life and specifically suggest human serum albumin (section 0050). Thus, one would have been motivated to fuse the Thy-1 fragment to human serum albumin. With respect to the fragments, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length (page 18 2nd paragraph). Haber teach that peptides can be generated by methods known in the art (page 18 2nd paragraph). Haber teach that the Thy-1 fragment can be in the form of a fusion protein (page 21 lines 27-30) and recognize the presence of proteases (page 1 lines 13-16). Haber recognizes that Cys111 in Thy1 is a possible site of undesired nonspecific disulfide linkages (page 15 first paragraph). Thus, one would have been motivated to make fragments including a 50 residue fragment containing residues 1-50 of SEQ ID NO:2 of Haber. Since Haber teach pharmaceutical compositions comprising a pharmaceutically acceptable carrier (pages 18-19 connecting paragraph) one would have been motivated to make such compositions. Since Haber teach that the compositions may be delivered by a catheter and also teach that the composition can be delivered by a device with the therapeutic compound (page 19 first paragraph) one would have been motivated to prepare such compositions. One would have had a reasonable expectation of success since Haber teach that peptides can be generated by methods known in the art (page 18 2nd paragraph) and Haber teach generation of fusions (page 15). Phipps recognizes the use of an amount effective for the desired result (section 0088). Based on the beneficial results taught by Wong and since Wong refers to fibrosis of different origins (page 2) one would be motivated to administer to other organs. Phipps recognize human tissues (section 0004) and human subjects (section 0081) as well as the heart and liver (sections 0004 and 0081). One would have had a reasonable expectation of success since Wong teach that soluble Thy-1 reverses pulmonary fibrosis (title). Further, Phipps teach that the polypeptides can be prepared by known methods including peptide synthesis or recombinant expression (section 0061) and recognizes that the administration can be by inhalation or intravenous (section 0086).
In relation to the subject of claims 2 and 8-9, Wong teach that soluble Thy-1 reverses pulmonary fibrosis (title) and Wong teach that mice in which fibrosis was established were administered the agent which reduced fibrosis scores and lung dysfunction (page 2). Claims 8-9 refer to inhibiting or preventing so the subject of claim 8 for example is not required to have any preexisting alveolar septal thickness.
In relation to the polypeptide of claims 2, 8-9 and 14, as discussed above the prior art suggests (residues 1-50 of SEQ ID NO:2 of Haber) fusion to human serum albumin. Residues 16-18 of SEQ ID NO:2 are RLD and residues 37-41 are RETKK (interpreted to be syndecan-4 binding domain). Phipps teach polypeptides in which the GPI anchor is removed (section 0054).
In relation to claims 3-4, Wong refers to both ‘self limited’ (3rd line of abstract on page 2) and ‘persistent’ (4th line of abstract on page 2) as well as ‘after fibrosis was established’ (line 14 of abstract on page 2).
In relation to claim 5, Wong teach that soluble Thy-1 reverses pulmonary fibrosis (title) and teach that mice in which fibrosis was established were administered Thy1-IgGFc which reduced fibrosis scores and lung dysfunction (page 2).
In relation to claim 6, Wong recites IPF (idiopathic pulmonary fibrosis) (4th line of abstract on page 2).
In relation to claim 7, Wong teach that exogenous sThy1 has therapeutic effects on fibrosis of different origins (page 2). Phipps recognize human tissues (section 0004) and human subjects (section 0081) as well as the heart and liver (sections 0004 and 0081).
In relation to claim 10, Phipps recognizes that the administration can be by inhalation (section 0086).
In relation to claims 11 and 35, Wong recites administration of Thy1-IgG Fc 14 days after bleomycin in mice (page 2). Such description appears to be the same as that in the instant specification (sections 0023 and 0150) which refers to human and intravenous. Further, Phipps recognizes that the administration can be intravenous (section 0086). Phipps recognizes human Thy1 (sections 0045-0046).
In relation to claim 16, Wong mentions the use of a human lung fibroblasts (page 2). Phipps recognize human tissues (section 0004) and human subjects (section 0081).
Response to Arguments - 103
Applicant's arguments filed 5/7/25 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that there is nothing in Haber to suggest deleting Cys111, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length but could be 10 amino acids in length (page 18 2nd paragraph). A 50 amino acid peptide or 10 amino acid peptide does not necessarily contain residue 111. Wong teach that soluble Thy-1 reverses pulmonary fibrosis via its integrin-binding domain (title). Wong recites that the integrin-like binding domain is RLD (page 2). Thus, functional properties of the peptide are known to be present in small regions. Residues 16-18 of SEQ ID NO:2 of Haber are RLD which is far removed from Cys111.
Although applicants argue that Haber teaches away since there are other Cys residues to delete, the only residue mentioned by Haber in terms of possible nonspecific linkages is Cys111 (page 15 first paragraph). Although Haber does not elaborate on the other residues, there are numerous possible reasons why they were not considered to be possibly problematic. For example, certain residues may not be as accessible as residue 111. In the instant case, there are inadequate facts to conclude a teaching away because Haber only mentions Cys111. Further, with respect to functionality Wong teach that soluble Thy-1 reverses pulmonary fibrosis via its integrin-binding domain (title) and that the integrin-like binding domain is RLD (page 2). Residues 16-18 of SEQ ID NO:2 of Haber are RLD and residues 37-41 are RETKK (interpreted to be syndecan-4 binding domain) which are far removed from Cys111.
Although applicants argue that based on one calculation that there are 61 possible fragments, the mere possibility or alternatives is not necessarily a teaching away. MPEP 2143 E states: “when there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." KSR, 550 U.S. at 402-03, 82 USPQ2d at 1390.” In the instant case, Haber teach human as a source of the Thy-1 (page 2 first paragraph and amino acids 1-111 of SEQ ID NO: 2) which starts at the first residue after the signal sequence (see Table 3 on page 4). With respect to the fragments, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length (page 18 2nd paragraph) which correspond to a finite number of fragments.
Although applicants argue there is no reason as to why one would have made a fragment, Haber teach that the compound comprise an extracellular fragment of Thy-1 (claim 4). Haber teach an example with a rat extracellular fragment of residues Gln1-Gly113 (page 13 last paragraph). Haber teach human as a source of the Thy-1 (page 2 first paragraph and amino acids 1-111 of SEQ ID NO: 2) which starts at the first residue after the signal sequence (see Table 3 on page 4). With respect to the fragments, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length (page 18 2nd paragraph). Thus, one would have been motivated by the express teachings and suggestions of Haber. Further, Wong teach that soluble Thy-1 reverses pulmonary fibrosis via its integrin-binding domain (title). Wong recites that the integrin-like binding domain is RLD (page 2). Thus, functional properties of this protein are known and have been correlated to a specific sequence. MPEP 2144 recognizes that the reason or motivation to modify a reference does not have to be the same as the applicants. With respect to the Thy-1 fragments, Haber teach that the fragments will ordinarily be preferably 50 contiguous amino acids in length (page 18 2nd paragraph). Haber teach human as a source of the Thy-1 (page 2 first paragraph and SEQ ID NO: 2, 119 amino acids in length). Since Haber recognizes that Cys111 in Thy1 is a possible site of undesired nonspecific disulfide linkages (page 15 first paragraph) one would have been motivated to make peptides comprising fragments in which Cys111 has been deleted. Further, Phipps recognizes that residues 1-19 of Thy-1 are a signal peptide which is cleaved to form the mature and soluble form (figure 1a). Thus, one would have been motivated to make fragments including a 50 residue fragment containing residues 1-50 of SEQ ID NO:2 of Haber.
Although applicants argue about hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Although applicants argue that Phipps alone does not teach the invention, 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).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658